1 00:00:01,530 --> 00:00:02,730 [Lecturer] All right. 2 00:00:02,730 --> 00:00:03,640 We are 3 00:00:04,800 --> 00:00:09,000 talking about congenital anomalies, basic dysmorphology 4 00:00:09,000 --> 00:00:10,353 and genetic assessment. 5 00:00:11,490 --> 00:00:16,490 This lecture uses slides that go along with the chapter 6 00:00:16,680 --> 00:00:20,610 in the BRE genetics nursing book. 7 00:00:20,610 --> 00:00:23,380 And I have added to them quite a bit 8 00:00:24,360 --> 00:00:25,860 to 9 00:00:25,860 --> 00:00:28,140 fill out the information 10 00:00:28,140 --> 00:00:31,680 and the value of the basic overview. 11 00:00:31,680 --> 00:00:33,330 So 12 00:00:33,330 --> 00:00:35,553 we will proceed now. 13 00:00:36,420 --> 00:00:37,650 So 14 00:00:37,650 --> 00:00:39,180 I wanted to 15 00:00:39,180 --> 00:00:43,050 frame the discussion about dysmorphology 16 00:00:43,050 --> 00:00:46,890 in the context of clinical assessment process 17 00:00:46,890 --> 00:00:49,540 and our overall aim in 18 00:00:51,450 --> 00:00:55,140 clinical genetics diagnosis of 19 00:00:55,140 --> 00:00:58,530 collecting a set of information 20 00:00:58,530 --> 00:01:01,740 that we, basically, use pattern recognition, 21 00:01:01,740 --> 00:01:05,550 or human skills in pattern recognition 22 00:01:05,550 --> 00:01:06,840 to 23 00:01:06,840 --> 00:01:11,840 identify a pattern that is quote, "recognizable, end quote. 24 00:01:12,690 --> 00:01:15,210 So our clinical 25 00:01:15,210 --> 00:01:16,620 exam 26 00:01:16,620 --> 00:01:21,510 basically goes through a set of features. 27 00:01:21,510 --> 00:01:23,520 We look for features, 28 00:01:23,520 --> 00:01:25,380 and we list the ones that we find, 29 00:01:25,380 --> 00:01:28,260 feature A, feature B, feature C, 30 00:01:28,260 --> 00:01:30,180 and we 31 00:01:30,180 --> 00:01:32,820 then take that 32 00:01:32,820 --> 00:01:33,690 feature set 33 00:01:33,690 --> 00:01:37,150 and see if we recognize a pattern 34 00:01:38,100 --> 00:01:39,280 that is 35 00:01:41,310 --> 00:01:44,070 typical of or almost typical of 36 00:01:44,070 --> 00:01:46,620 what is seen in a particular disorder 37 00:01:46,620 --> 00:01:50,670 and a pattern that is not broadly seen in other disorders 38 00:01:50,670 --> 00:01:52,950 or in normal individuals. 39 00:01:52,950 --> 00:01:54,810 So that's really our goal. 40 00:01:54,810 --> 00:01:58,830 So we come up with, from the pattern analysis, 41 00:01:58,830 --> 00:02:00,990 a differential diagnosis 42 00:02:00,990 --> 00:02:04,470 of a set of disorders that this might represent. 43 00:02:04,470 --> 00:02:06,630 Sometimes it's very clear there's only one, 44 00:02:06,630 --> 00:02:07,463 sometimes 45 00:02:08,820 --> 00:02:09,750 it's complicated, 46 00:02:09,750 --> 00:02:12,540 and you might put a list of three or four disorders 47 00:02:12,540 --> 00:02:13,533 or maybe more. 48 00:02:14,820 --> 00:02:17,460 The feature set can also rule out disorders. 49 00:02:17,460 --> 00:02:19,140 So you might start out 50 00:02:19,140 --> 00:02:22,080 with a pretty long differential diagnosis list 51 00:02:22,080 --> 00:02:25,290 and then cross things out because key, 52 00:02:25,290 --> 00:02:28,860 or characteristic features of a disorder are not present 53 00:02:28,860 --> 00:02:30,060 or there are other features 54 00:02:30,060 --> 00:02:33,250 that make it pretty unlikely that disorder 55 00:02:34,350 --> 00:02:36,480 should be considered any further. 56 00:02:36,480 --> 00:02:39,810 So both adding and subtracting disorders 57 00:02:39,810 --> 00:02:44,810 from the differential diagnosis is our intermediate goal. 58 00:02:44,940 --> 00:02:48,900 And then once we have that list, we can say 59 00:02:48,900 --> 00:02:53,490 is there additional testing, additional clinical information 60 00:02:53,490 --> 00:02:57,120 that can help us differentiate between those 61 00:02:57,120 --> 00:02:59,490 or should we just send it on to someone 62 00:02:59,490 --> 00:03:02,850 who knows a little bit more about these kinds of things 63 00:03:02,850 --> 00:03:04,600 and what the most efficient 64 00:03:06,450 --> 00:03:07,773 next steps are? 65 00:03:09,480 --> 00:03:13,170 So I listed feature A, feature B and feature C 66 00:03:13,170 --> 00:03:16,320 as clinical things we find, for example, on exam, 67 00:03:16,320 --> 00:03:18,510 but the pattern is really 68 00:03:18,510 --> 00:03:20,940 a multi-axial 69 00:03:20,940 --> 00:03:22,110 data set. 70 00:03:22,110 --> 00:03:24,150 So you have the physical exam features 71 00:03:24,150 --> 00:03:26,763 but there's also things about the history, 72 00:03:28,170 --> 00:03:30,243 when did the obesity start, 73 00:03:31,680 --> 00:03:36,680 what were the early speech development history, 74 00:03:36,690 --> 00:03:38,070 those kinds of things, 75 00:03:38,070 --> 00:03:39,993 as well as family history, 76 00:03:41,310 --> 00:03:42,243 behavior. 77 00:03:43,440 --> 00:03:47,703 This is something that is often overlooked, is specific, 78 00:03:50,580 --> 00:03:54,550 I would say characteristic behaviors are 79 00:03:55,560 --> 00:03:57,930 observed in a number of disorders, 80 00:03:57,930 --> 00:04:00,730 and the presence or absence of those behaviors 81 00:04:02,280 --> 00:04:04,110 or personality traits 82 00:04:04,110 --> 00:04:07,840 or speech characteristics can sometimes really help you 83 00:04:09,630 --> 00:04:12,033 narrow down that differential from the pattern. 84 00:04:13,560 --> 00:04:16,350 We'll talk a little bit about measurements. 85 00:04:16,350 --> 00:04:19,780 I'm trying to move from a subjective feature 86 00:04:22,260 --> 00:04:26,160 declaration to something that is objective. 87 00:04:26,160 --> 00:04:27,780 And 88 00:04:27,780 --> 00:04:28,860 also 89 00:04:28,860 --> 00:04:29,940 the 90 00:04:29,940 --> 00:04:34,230 value of testing and lab results, 91 00:04:34,230 --> 00:04:38,160 usual types of non-genetic testing 92 00:04:38,160 --> 00:04:40,653 will also potentially fit into the pattern. 93 00:04:42,030 --> 00:04:44,400 And finally, tests 94 00:04:44,400 --> 00:04:46,590 or assessments such as 95 00:04:46,590 --> 00:04:48,910 IQ or a developmental assessment 96 00:04:50,655 --> 00:04:53,490 and the outcomes of that will also be very important 97 00:04:53,490 --> 00:04:55,480 in trying to 98 00:04:57,450 --> 00:05:01,170 create a full, rich pattern set 99 00:05:01,170 --> 00:05:02,760 to 100 00:05:02,760 --> 00:05:06,510 help us differentiate what disorders we're really looking in 101 00:05:06,510 --> 00:05:10,530 or what are the next scanning types of genetic testing, 102 00:05:10,530 --> 00:05:12,960 which we'll talk about in a later module, 103 00:05:12,960 --> 00:05:16,080 that are going to be most productive 104 00:05:16,080 --> 00:05:18,423 in trying to understand what's going on. 105 00:05:19,470 --> 00:05:20,303 So 106 00:05:21,510 --> 00:05:25,383 we have, essentially, defined a process here, 107 00:05:26,310 --> 00:05:30,840 but it's worth recognizing that the process is, essentially, 108 00:05:30,840 --> 00:05:34,200 going from effect backwards toward cause. 109 00:05:34,200 --> 00:05:38,160 So we're trying to understand what the underlying cause is 110 00:05:38,160 --> 00:05:41,550 in terms of the genetics, the proteins, the functions, 111 00:05:41,550 --> 00:05:43,120 and how that 112 00:05:44,280 --> 00:05:47,130 relates to effect 'cause we're not there 113 00:05:47,130 --> 00:05:49,530 when the embryo is developing 114 00:05:49,530 --> 00:05:53,760 or when the brain is developing and during the fetal growth. 115 00:05:53,760 --> 00:05:57,840 What we can see is the downstream effects of that, 116 00:05:57,840 --> 00:06:01,710 and so we are trying to capture those downstream effects 117 00:06:01,710 --> 00:06:04,090 and then work, in our brain, backwards toward 118 00:06:06,944 --> 00:06:10,350 a sense of what are the kinds of things that went wrong 119 00:06:10,350 --> 00:06:15,350 or went different during embryonic or fetal development. 120 00:06:18,360 --> 00:06:19,193 All right. 121 00:06:19,193 --> 00:06:21,880 So dysmorphology is a 122 00:06:24,990 --> 00:06:27,750 area of genetics in which there are, 123 00:06:27,750 --> 00:06:29,733 of specialization, essentially. 124 00:06:30,570 --> 00:06:33,930 And it comes from, I think it's probably Greek, 125 00:06:33,930 --> 00:06:36,270 dys for painful and morph for shape, 126 00:06:36,270 --> 00:06:38,700 so painful shape, not really so much. 127 00:06:38,700 --> 00:06:41,400 I think it's really things that are different, 128 00:06:41,400 --> 00:06:43,170 and noticeably different. 129 00:06:43,170 --> 00:06:45,390 And it's really the study of congenital anomalies 130 00:06:45,390 --> 00:06:48,123 or abnormal patterns of development. 131 00:06:49,440 --> 00:06:51,870 Not all of them are genetic. 132 00:06:51,870 --> 00:06:53,190 All right. 133 00:06:53,190 --> 00:06:56,880 So first step is identification of anomalies 134 00:06:56,880 --> 00:06:58,920 can lead to an accurate diagnosis. 135 00:06:58,920 --> 00:07:02,550 So why do we study dysmorphology? 136 00:07:02,550 --> 00:07:05,283 Accurate diagnosis can guide clinical management. 137 00:07:06,270 --> 00:07:08,080 And we can consider 138 00:07:09,630 --> 00:07:11,820 with that information within the context of the family, 139 00:07:11,820 --> 00:07:15,030 as I showed on the first slide, 140 00:07:15,030 --> 00:07:17,310 and we try to develop that pattern. 141 00:07:17,310 --> 00:07:20,130 So here's an example of a feature pattern 142 00:07:20,130 --> 00:07:22,683 for a syndrome called Noonan syndrome. 143 00:07:23,820 --> 00:07:26,400 And I'm going to read through these. 144 00:07:26,400 --> 00:07:28,470 Triangular-shaped face, widely spaced eyes, 145 00:07:28,470 --> 00:07:32,310 downward-slanting palpebral fissures, 146 00:07:32,310 --> 00:07:33,143 drooping eyelids, 147 00:07:33,143 --> 00:07:36,573 or ptosis, P-T-O-S-I-S, ptosis, 148 00:07:37,620 --> 00:07:41,550 low set ears, high or prominent nasal bridge, 149 00:07:41,550 --> 00:07:43,620 short webbed neck. 150 00:07:43,620 --> 00:07:45,360 Those are actually two different things. 151 00:07:45,360 --> 00:07:46,800 A short neck is a short neck 152 00:07:46,800 --> 00:07:48,450 and a webbed neck is a webbed neck, 153 00:07:48,450 --> 00:07:49,983 sometimes they occur together. 154 00:07:51,210 --> 00:07:53,160 And congenital heart defects, 155 00:07:53,160 --> 00:07:54,480 in particular Noonan syndrome, 156 00:07:54,480 --> 00:07:57,180 you look for pulmonic stenosis, 157 00:07:57,180 --> 00:08:00,090 the stenosis of the pulmonic valve. 158 00:08:00,090 --> 00:08:03,870 And occasionally we'll pick up a kid with Noonan syndrome 159 00:08:03,870 --> 00:08:06,520 because the cardiologist identifies 160 00:08:07,620 --> 00:08:11,310 pulmonic stenosis, even a mild pulmonic stenosis. 161 00:08:11,310 --> 00:08:13,590 And the clinical features are not so obvious, 162 00:08:13,590 --> 00:08:16,470 but when we take a look, there's enough suspicion, 163 00:08:16,470 --> 00:08:18,930 and we do genetic testing and identify 164 00:08:18,930 --> 00:08:21,090 that this patient really does have Noonan syndrome. 165 00:08:21,090 --> 00:08:22,590 Okay. 166 00:08:22,590 --> 00:08:23,850 So 167 00:08:23,850 --> 00:08:25,380 what are these features? 168 00:08:25,380 --> 00:08:27,120 So we put them in words 169 00:08:27,120 --> 00:08:30,390 when we put them in our notes in the chart, 170 00:08:30,390 --> 00:08:31,740 and we put them in words 171 00:08:31,740 --> 00:08:34,143 when we write a paper about a disorder, 172 00:08:35,280 --> 00:08:36,990 and we put them in words 173 00:08:36,990 --> 00:08:39,190 when we're searching through databases 174 00:08:40,710 --> 00:08:41,543 to 175 00:08:41,543 --> 00:08:46,410 try to find a match for a feature or pattern 176 00:08:46,410 --> 00:08:47,440 that we're not 177 00:08:48,330 --> 00:08:50,160 recognizing upfront. 178 00:08:50,160 --> 00:08:52,050 I do a lot of that. 179 00:08:52,050 --> 00:08:56,580 So one of the challenges is in converting 180 00:08:56,580 --> 00:09:00,150 what you see on exam or what you feel on exam 181 00:09:00,150 --> 00:09:03,090 to one of these terms, 182 00:09:03,090 --> 00:09:07,140 one of these verbal, word-based terms. 183 00:09:07,140 --> 00:09:08,550 So I'm gonna show you some pictures 184 00:09:08,550 --> 00:09:11,400 that go along with these features. 185 00:09:11,400 --> 00:09:13,500 First one is triangular face. 186 00:09:13,500 --> 00:09:14,940 So you can see from these pictures, 187 00:09:14,940 --> 00:09:16,320 these two boys 188 00:09:16,320 --> 00:09:18,690 have a triangular face, 189 00:09:18,690 --> 00:09:20,460 and it's much wider at the top 190 00:09:20,460 --> 00:09:23,373 and much narrower at the bottom of the face. 191 00:09:25,590 --> 00:09:27,450 Wide-spaced eyes, 192 00:09:27,450 --> 00:09:28,650 or 193 00:09:28,650 --> 00:09:33,330 the old-fashioned technical term is hypertelorism, 194 00:09:33,330 --> 00:09:37,380 meaning that the center of the eyeballs, not the edges, 195 00:09:37,380 --> 00:09:38,460 but the center of the eyeballs, 196 00:09:38,460 --> 00:09:40,060 we measure that from the pupils, 197 00:09:40,950 --> 00:09:44,103 measures wider than usual. 198 00:09:45,240 --> 00:09:50,190 This patient also has two other dysmorphic features 199 00:09:50,190 --> 00:09:55,190 that I'll let you try to figure out from these pictures. 200 00:09:55,650 --> 00:09:59,610 The third one is downward-slanting palpebral fissures. 201 00:09:59,610 --> 00:10:01,290 The palpebral fissures being 202 00:10:01,290 --> 00:10:04,440 the opening between the upper and lower eyelids. 203 00:10:04,440 --> 00:10:07,230 And this patient has, 204 00:10:07,230 --> 00:10:11,313 basically, if you draw a line from the inner canthus, 205 00:10:12,870 --> 00:10:14,910 try and get you an arrow here, 206 00:10:14,910 --> 00:10:18,390 the inner canthus to the outer canthus, it's not horizontal, 207 00:10:18,390 --> 00:10:19,720 it goes down 208 00:10:20,700 --> 00:10:22,530 on both sides typically. 209 00:10:22,530 --> 00:10:26,850 This patient also has proptosis, prominence of the eyes, 210 00:10:26,850 --> 00:10:31,850 eyes that stick out almost to or beyond the eyebrow arch 211 00:10:34,470 --> 00:10:37,590 and relatively-large looking eyes. 212 00:10:37,590 --> 00:10:38,423 All right. 213 00:10:38,423 --> 00:10:39,990 The next feature is drooping eyelids, 214 00:10:39,990 --> 00:10:42,423 or ptosis, P-T-O-S-I-S. 215 00:10:43,530 --> 00:10:46,170 Here's a girl with unilateral ptosis. 216 00:10:46,170 --> 00:10:49,410 She has an eyelid that droops down over the other one. 217 00:10:49,410 --> 00:10:51,420 It's more obvious when it's unilateral, 218 00:10:51,420 --> 00:10:54,420 but in Noonan syndrome, it's usually bilateral. 219 00:10:54,420 --> 00:10:55,530 And one of the things 220 00:10:55,530 --> 00:10:59,310 that individuals with significant ptosis do 221 00:10:59,310 --> 00:11:01,540 is that they tilt their heads back 222 00:11:02,640 --> 00:11:07,500 because they need to look under their low-lying eyelids 223 00:11:07,500 --> 00:11:10,050 in order to see well. 224 00:11:10,050 --> 00:11:12,480 So sometimes they don't know that they're doing this, 225 00:11:12,480 --> 00:11:15,577 and you can lift their eyelids up and say, 226 00:11:15,577 --> 00:11:16,710 "Is that better?" 227 00:11:16,710 --> 00:11:18,210 And if it is better, 228 00:11:18,210 --> 00:11:20,730 then they may need to go see an ophthalmologist 229 00:11:20,730 --> 00:11:23,460 to see if they need some surgical management 230 00:11:23,460 --> 00:11:25,113 of their ptosis. 231 00:11:26,070 --> 00:11:27,810 Low set ears, 232 00:11:27,810 --> 00:11:30,360 basically the ears fall. 233 00:11:30,360 --> 00:11:35,340 This is a line drawn between the inner canthi of the eyes. 234 00:11:35,340 --> 00:11:36,300 And 235 00:11:36,300 --> 00:11:39,390 if the outer helix, 236 00:11:39,390 --> 00:11:42,450 or the root of the helix fall significantly below that line, 237 00:11:42,450 --> 00:11:45,090 then that's low set ears. 238 00:11:45,090 --> 00:11:48,600 Ears can also be rotated, in the case of Noonans 239 00:11:48,600 --> 00:11:50,493 are often rotated posteriorly. 240 00:11:52,230 --> 00:11:55,080 I'm gonna point you back over to this kiddo here. 241 00:11:55,080 --> 00:11:58,980 If you draw a line between his inner canthi here, 242 00:11:58,980 --> 00:12:01,140 then you will see that that line, 243 00:12:01,140 --> 00:12:02,790 his whole ear is below that. 244 00:12:02,790 --> 00:12:05,583 So he has low set ears as well. 245 00:12:07,050 --> 00:12:07,883 A high, 246 00:12:07,883 --> 00:12:09,810 or prominent nasal bridge 247 00:12:09,810 --> 00:12:13,890 means this part of the nose between the eyes, 248 00:12:13,890 --> 00:12:16,440 part of the nose between the eyes, that's the bridge. 249 00:12:16,440 --> 00:12:19,410 And it is high when 250 00:12:19,410 --> 00:12:20,430 it 251 00:12:20,430 --> 00:12:23,040 sticks out further than average. 252 00:12:23,040 --> 00:12:26,910 And in a couple of these, forms of a continuous line 253 00:12:26,910 --> 00:12:31,023 without a dip between the forehead and the tip of the nose. 254 00:12:33,091 --> 00:12:34,170 The webbed neck. 255 00:12:34,170 --> 00:12:36,510 Here's a couple pictures of webbed neck. 256 00:12:36,510 --> 00:12:38,590 These are usually the result of 257 00:12:39,570 --> 00:12:42,180 backed up lymphatics around the neck, 258 00:12:42,180 --> 00:12:44,190 posterior neck in particular 259 00:12:44,190 --> 00:12:45,390 in 260 00:12:45,390 --> 00:12:49,470 the early or mid embryonic life. 261 00:12:49,470 --> 00:12:52,950 And these are the residua of those. 262 00:12:52,950 --> 00:12:55,953 So these are both webbed necks. 263 00:12:57,360 --> 00:13:00,573 And sometimes they're more apparent from behind. 264 00:13:02,160 --> 00:13:02,993 Okay. 265 00:13:02,993 --> 00:13:04,410 So the other one I missed there 266 00:13:04,410 --> 00:13:06,840 was congenital heart defects, Noonan syndrome, 267 00:13:06,840 --> 00:13:08,943 and we already talked about that. 268 00:13:10,800 --> 00:13:11,633 All right. 269 00:13:12,660 --> 00:13:13,950 Major anomalies. 270 00:13:13,950 --> 00:13:15,780 So we divide the anomalies 271 00:13:15,780 --> 00:13:17,550 between those that are major and minor. 272 00:13:17,550 --> 00:13:19,890 Major anomalies are serious, 273 00:13:19,890 --> 00:13:21,660 things like cognitive impairment, 274 00:13:21,660 --> 00:13:24,840 which really is a malformation of the brain. 275 00:13:24,840 --> 00:13:28,140 It's often due, not necessarily to things 276 00:13:28,140 --> 00:13:30,990 that are visually structurally different 277 00:13:30,990 --> 00:13:33,210 on an MRI or a CT scan, 278 00:13:33,210 --> 00:13:35,010 but a difference in the organization 279 00:13:35,010 --> 00:13:39,000 of the neural layers in the brain as it develops, 280 00:13:39,000 --> 00:13:41,100 and that affects the efficiency 281 00:13:41,100 --> 00:13:44,910 of information management in the brain. 282 00:13:44,910 --> 00:13:47,130 Heart defects, renal agenesis. 283 00:13:47,130 --> 00:13:50,250 So those are examples of major anomalies 284 00:13:50,250 --> 00:13:53,050 that often require medical or surgical attention 285 00:13:53,910 --> 00:13:57,060 and can have life-threatening implications 286 00:13:57,060 --> 00:13:59,253 or serious cosmetic effects. 287 00:14:00,150 --> 00:14:01,710 Okay. 288 00:14:01,710 --> 00:14:04,440 Minor anomalies typically have no serious functional 289 00:14:04,440 --> 00:14:06,510 or cosmetic consequences, 290 00:14:06,510 --> 00:14:09,810 and so they're treated mostly as clues 291 00:14:09,810 --> 00:14:13,020 toward an underlying disease process. 292 00:14:13,020 --> 00:14:14,890 Minor anomalies also 293 00:14:15,930 --> 00:14:17,820 can be seen in 294 00:14:17,820 --> 00:14:21,000 a unaffected population, 295 00:14:21,000 --> 00:14:23,340 but they're usually not very common. 296 00:14:23,340 --> 00:14:24,810 Somebody made up a number and said 297 00:14:24,810 --> 00:14:28,410 it's found in fewer than 4% of the population. 298 00:14:28,410 --> 00:14:29,640 Not sure that that's 299 00:14:29,640 --> 00:14:31,290 necessarily a number to hang your hat on, 300 00:14:31,290 --> 00:14:34,800 but the idea is minor anomalies are called anomalies 301 00:14:34,800 --> 00:14:37,353 because they're not present in most everybody. 302 00:14:38,190 --> 00:14:39,840 But they can be present in people 303 00:14:40,890 --> 00:14:43,473 without a genetic dysmorphic condition. 304 00:14:44,430 --> 00:14:46,923 Most dysmorphic features are classified as minor, 305 00:14:48,120 --> 00:14:51,660 and several minor anomalies appearing together 306 00:14:51,660 --> 00:14:54,540 can be enough if that pattern 307 00:14:54,540 --> 00:14:57,660 is rare enough and unique enough 308 00:14:57,660 --> 00:15:00,393 to lead you toward a correct diagnosis. 309 00:15:01,830 --> 00:15:02,663 All right. 310 00:15:02,663 --> 00:15:07,410 Here's an example of a minor anomaly called clinodactyly. 311 00:15:07,410 --> 00:15:08,937 Dactyly of course referring to fingers 312 00:15:08,937 --> 00:15:11,253 and clino referring to a curve, 313 00:15:12,150 --> 00:15:13,800 so it's a 314 00:15:13,800 --> 00:15:14,850 curved digit. 315 00:15:14,850 --> 00:15:16,893 It's usually curved inward, 316 00:15:17,790 --> 00:15:19,713 as in this fifth digit here. 317 00:15:20,580 --> 00:15:22,800 It's often the fifth finger that's curved inward 318 00:15:22,800 --> 00:15:24,050 toward the other fingers. 319 00:15:25,950 --> 00:15:29,610 This fifth finger clinodactyly feature 320 00:15:29,610 --> 00:15:32,910 is found in 10% of the normal population, 321 00:15:32,910 --> 00:15:33,743 but it's a 322 00:15:34,800 --> 00:15:38,583 almost invariant feature of Down syndrome. 323 00:15:40,710 --> 00:15:43,380 I have seen a couple of Down syndrome kids 324 00:15:43,380 --> 00:15:47,580 in whom this feature was not really very prominent, 325 00:15:47,580 --> 00:15:49,830 so it doesn't necessarily rule it out, 326 00:15:49,830 --> 00:15:52,020 but you gotta question your diagnosis 327 00:15:52,020 --> 00:15:53,470 when you're not finding that. 328 00:15:54,870 --> 00:15:55,710 Okay. 329 00:15:55,710 --> 00:15:57,130 So we're talking about 330 00:15:59,610 --> 00:16:00,660 terminology again. 331 00:16:00,660 --> 00:16:03,780 So a malformation is a primary problem 332 00:16:03,780 --> 00:16:04,950 with growth or development. 333 00:16:04,950 --> 00:16:08,070 In other words, the growth or development program 334 00:16:08,070 --> 00:16:11,100 said, "Make it this way instead of the usual way." 335 00:16:11,100 --> 00:16:11,933 All right? 336 00:16:13,290 --> 00:16:15,690 An example is cleft lip, 337 00:16:15,690 --> 00:16:18,780 which is failure of the lip and or the palate tissues 338 00:16:18,780 --> 00:16:21,153 to fuse together during development. 339 00:16:21,990 --> 00:16:25,657 So there's something about the program that said, 340 00:16:25,657 --> 00:16:27,210 "You know, you've gone far enough, 341 00:16:27,210 --> 00:16:29,850 you don't have to really close this upper lip." 342 00:16:29,850 --> 00:16:33,810 And there wasn't anything that got in the way 343 00:16:33,810 --> 00:16:36,180 or anything that was toxic. 344 00:16:36,180 --> 00:16:37,713 That's a malformation. 345 00:16:39,330 --> 00:16:42,210 A deformation, in contrast, 346 00:16:42,210 --> 00:16:43,043 is 347 00:16:44,371 --> 00:16:45,240 a physical change 348 00:16:45,240 --> 00:16:49,260 that's due to a physical or mechanical force 349 00:16:49,260 --> 00:16:52,050 that is preventing the proper growth and development 350 00:16:52,050 --> 00:16:55,800 of a structure that would have otherwise developed. 351 00:16:55,800 --> 00:16:59,310 Examples are not enough space in the womb, 352 00:16:59,310 --> 00:17:00,630 so oligohydramnios, 353 00:17:00,630 --> 00:17:03,990 so not enough amniotic fluid. 354 00:17:03,990 --> 00:17:06,600 The baby's ear may be 355 00:17:06,600 --> 00:17:07,890 folded over 356 00:17:07,890 --> 00:17:11,550 and pressed against the inside of the womb 357 00:17:11,550 --> 00:17:13,230 for weeks at a time, 358 00:17:13,230 --> 00:17:16,800 and that may change its growth or position 359 00:17:16,800 --> 00:17:19,320 or how it looks when the baby comes out. 360 00:17:19,320 --> 00:17:24,150 Multiples means twins, triplets, quadruplets, whatever 361 00:17:24,150 --> 00:17:26,040 they tend to have, 362 00:17:26,040 --> 00:17:27,670 and can have 363 00:17:29,010 --> 00:17:30,420 deformation, 364 00:17:30,420 --> 00:17:32,550 areas of the body that were deformed 365 00:17:32,550 --> 00:17:35,163 by their local environment in the womb. 366 00:17:36,900 --> 00:17:40,830 A disruption is different again. 367 00:17:40,830 --> 00:17:43,110 It is a normal developmental process 368 00:17:43,110 --> 00:17:45,580 that is disrupted by an event 369 00:17:46,620 --> 00:17:49,593 that leads to the destruction of normal tissue. 370 00:17:50,730 --> 00:17:55,730 A drug exposure, a teratogenic drug exposure, 371 00:17:56,070 --> 00:17:59,613 prenatal trauma, vascular insufficiency. 372 00:18:02,205 --> 00:18:05,670 This may be something that's very unpredictable 373 00:18:05,670 --> 00:18:09,330 and there are examples of a number of features 374 00:18:09,330 --> 00:18:13,000 that are believed to result from 375 00:18:13,950 --> 00:18:16,600 a clotting of a particular 376 00:18:17,910 --> 00:18:19,260 anatomical field, 377 00:18:19,260 --> 00:18:21,960 a clotting of the arterial supply 378 00:18:21,960 --> 00:18:24,780 such that that arterial field 379 00:18:24,780 --> 00:18:27,870 stops growing or actually can involute 380 00:18:27,870 --> 00:18:31,620 because it has lost its blood supply. 381 00:18:31,620 --> 00:18:34,830 Some infections that target certain areas 382 00:18:34,830 --> 00:18:38,043 may also cause physical disruption. 383 00:18:39,780 --> 00:18:40,613 All right. 384 00:18:40,613 --> 00:18:42,873 This is an example of a disruption anomaly. 385 00:18:43,830 --> 00:18:46,650 So here's a child with 386 00:18:46,650 --> 00:18:51,650 a third digit, where the end of the digit is shriveled up, 387 00:18:52,170 --> 00:18:53,470 and it's got 388 00:18:55,710 --> 00:18:57,240 a belt line here, 389 00:18:57,240 --> 00:19:00,750 where somebody's cinched up a belt, it looks like, 390 00:19:00,750 --> 00:19:02,950 so this is probably a vascular 391 00:19:04,440 --> 00:19:06,090 event, where the tip of this finger 392 00:19:06,090 --> 00:19:07,893 lost its vascular supply. 393 00:19:08,790 --> 00:19:11,610 Those are not usually genetic, 394 00:19:11,610 --> 00:19:16,443 and so don't necessarily indicate a genetic syndrome. 395 00:19:17,940 --> 00:19:19,260 Okay. 396 00:19:19,260 --> 00:19:22,830 Another form of malformation is dysplasia, 397 00:19:22,830 --> 00:19:24,210 which means the alteration 398 00:19:24,210 --> 00:19:27,810 in the size, shape and organization of cells. 399 00:19:27,810 --> 00:19:31,080 And the most common cause of that is single disorders. 400 00:19:31,080 --> 00:19:34,260 And an excellent example is ectodermal dysplasia. 401 00:19:34,260 --> 00:19:37,950 So let's parse that down to 402 00:19:37,950 --> 00:19:38,910 dermal, 403 00:19:38,910 --> 00:19:40,200 so it has to do with the skin. 404 00:19:40,200 --> 00:19:44,130 The ectoderm is the outer layer of the embryo 405 00:19:44,130 --> 00:19:46,720 that leads to skin and a number of other 406 00:19:48,780 --> 00:19:51,270 elements including the GI tract, 407 00:19:51,270 --> 00:19:54,213 the inner linings of the GI tract. 408 00:19:55,290 --> 00:19:58,120 And ectodermal dysplasias also 409 00:19:59,010 --> 00:20:03,180 can affect ectodermal appendages such as nails, 410 00:20:03,180 --> 00:20:05,850 hair, lashes, 411 00:20:05,850 --> 00:20:07,410 mammary glands. 412 00:20:07,410 --> 00:20:09,972 Teeth are part of the ectoderm, 413 00:20:09,972 --> 00:20:13,890 so ectodermal dysplasias may affect 414 00:20:13,890 --> 00:20:18,030 the maturation of a number of features 415 00:20:18,030 --> 00:20:19,380 in 416 00:20:19,380 --> 00:20:20,970 the ectoderm, 417 00:20:20,970 --> 00:20:23,463 and that's a dysplastic pattern. 418 00:20:27,090 --> 00:20:28,110 So what's a syndrome? 419 00:20:28,110 --> 00:20:30,600 So a syndrome is a collection of features 420 00:20:30,600 --> 00:20:33,840 that occur together and have a consistent pattern. 421 00:20:33,840 --> 00:20:36,330 They're thought to have the same cause. 422 00:20:36,330 --> 00:20:38,310 And an example is Down syndrome, 423 00:20:38,310 --> 00:20:39,240 which we've touched on 424 00:20:39,240 --> 00:20:42,330 a number of times in this course already. 425 00:20:42,330 --> 00:20:43,650 So think of a syndrome 426 00:20:43,650 --> 00:20:46,050 as this collection of features that occur together, 427 00:20:46,050 --> 00:20:50,100 have a consistent pattern that is not commonly seen 428 00:20:50,100 --> 00:20:52,983 outside of individuals with the syndrome. 429 00:20:55,020 --> 00:20:55,853 All right. 430 00:20:55,853 --> 00:20:58,180 What's the difference between a syndrome and a sequence? 431 00:21:00,151 --> 00:21:01,830 So a syndrome, I'm gonna go back. 432 00:21:01,830 --> 00:21:04,740 A syndrome is thought to have, 433 00:21:04,740 --> 00:21:06,660 all of the features are thought to arise 434 00:21:06,660 --> 00:21:08,790 from the same underlying cause. 435 00:21:08,790 --> 00:21:10,140 Okay? 436 00:21:10,140 --> 00:21:13,680 A sequence is where some of the features 437 00:21:13,680 --> 00:21:16,080 are actually secondary 438 00:21:16,080 --> 00:21:20,280 to a primary single anatomical cause. 439 00:21:20,280 --> 00:21:22,560 So one anomaly starts a chain reaction 440 00:21:22,560 --> 00:21:25,770 that causes another problem, which then causes another 441 00:21:25,770 --> 00:21:27,540 and then sometimes another. 442 00:21:27,540 --> 00:21:31,230 And the typical example of that is Pierre-Robin sequence, 443 00:21:31,230 --> 00:21:33,930 not syndrome but sequence. 444 00:21:33,930 --> 00:21:35,850 It begins with 445 00:21:35,850 --> 00:21:40,263 a micrognathia, a small jaw, a very small jaw, 446 00:21:41,490 --> 00:21:45,750 which is a growth defect in the mandible 447 00:21:45,750 --> 00:21:47,700 in the developing fetus. 448 00:21:47,700 --> 00:21:52,503 And what it results in is less room for the tongue. 449 00:21:53,340 --> 00:21:55,710 The tongue is hanging out there 450 00:21:55,710 --> 00:21:57,120 and 451 00:21:57,120 --> 00:21:59,670 is not allowing 452 00:21:59,670 --> 00:22:04,050 the two shelves of the pallet to flow together 453 00:22:04,050 --> 00:22:06,900 because tongue is occupying space 454 00:22:06,900 --> 00:22:09,360 that is higher than normal 455 00:22:09,360 --> 00:22:13,590 because its normal lower position is not there. 456 00:22:13,590 --> 00:22:15,030 I mean, the room is too small. 457 00:22:15,030 --> 00:22:17,433 You booked too small of a birth on the train. 458 00:22:20,250 --> 00:22:22,890 And the tongue may also be forced backwards, 459 00:22:22,890 --> 00:22:26,250 which can lead to respiratory obstruction as well. 460 00:22:26,250 --> 00:22:28,660 So kids with it, that are born with severely 461 00:22:31,200 --> 00:22:35,430 small jaws often have two things going on. 462 00:22:35,430 --> 00:22:37,470 They have a cleft palate 463 00:22:37,470 --> 00:22:40,050 because the palate wasn't allowed to close, 464 00:22:40,050 --> 00:22:41,670 and 465 00:22:41,670 --> 00:22:45,610 they have a high risk of respiratory obstruction 466 00:22:46,590 --> 00:22:47,890 at the base of the tongue. 467 00:22:49,500 --> 00:22:50,700 All right. 468 00:22:50,700 --> 00:22:51,990 What's an association? 469 00:22:51,990 --> 00:22:53,650 So these are all terms that we 470 00:22:55,140 --> 00:22:56,170 use to 471 00:22:57,150 --> 00:22:58,030 explain 472 00:22:59,910 --> 00:23:02,820 the difference between things that are 473 00:23:02,820 --> 00:23:04,290 genetically programmed, 474 00:23:04,290 --> 00:23:07,780 and things that we observe together 475 00:23:08,760 --> 00:23:09,960 for different reasons. 476 00:23:09,960 --> 00:23:13,680 So an association is a collection of features 477 00:23:13,680 --> 00:23:15,780 that occurs together 478 00:23:15,780 --> 00:23:18,183 but the causal relationship is not clear. 479 00:23:19,020 --> 00:23:21,450 And sometimes when we learn more, 480 00:23:21,450 --> 00:23:25,110 the name may change to a syndrome or sequence, 481 00:23:25,110 --> 00:23:26,190 but sometimes it doesn't. 482 00:23:26,190 --> 00:23:29,220 So for example, the VACTERL, 483 00:23:29,220 --> 00:23:32,523 or V-A-T-E-R is a shorter version of that, 484 00:23:33,780 --> 00:23:36,450 association is one 485 00:23:36,450 --> 00:23:39,780 which has overlap with genetic syndromes 486 00:23:39,780 --> 00:23:43,980 that are caused by single genetic changes, 487 00:23:43,980 --> 00:23:45,540 but we 488 00:23:45,540 --> 00:23:47,310 often see 489 00:23:47,310 --> 00:23:50,580 patients who rule out for those other syndromes 490 00:23:50,580 --> 00:23:53,790 who still have this pattern of features. 491 00:23:53,790 --> 00:23:56,340 It's not a syndrome but an association 492 00:23:56,340 --> 00:23:58,410 because we see them together 493 00:23:58,410 --> 00:24:02,340 but they don't clearly have a common cause. 494 00:24:02,340 --> 00:24:05,373 VACTERL is an acronym that stands for vertebral anomalies, 495 00:24:07,230 --> 00:24:08,890 anal stenosis or 496 00:24:09,750 --> 00:24:10,593 atresia, 497 00:24:11,850 --> 00:24:13,680 cardiac anomalies, 498 00:24:13,680 --> 00:24:15,513 tracheaesophageal fistula, 499 00:24:17,605 --> 00:24:20,620 renal anomalies, renal or collecting-system anomalies 500 00:24:21,510 --> 00:24:23,530 and limb anomalies, particularly 501 00:24:25,110 --> 00:24:25,943 radial rays. 502 00:24:25,943 --> 00:24:30,263 So the thumb, the base of the thumb and the radius 503 00:24:31,740 --> 00:24:33,723 of hands and arms. 504 00:24:36,750 --> 00:24:40,360 So a gestalt is a German word that basically means 505 00:24:41,850 --> 00:24:43,630 it really looks like 506 00:24:44,940 --> 00:24:48,513 it has this undefinable, 507 00:24:52,955 --> 00:24:57,090 undissectable feeling that's recognizable. 508 00:24:57,090 --> 00:24:59,220 So it's an overall impression, 509 00:24:59,220 --> 00:25:01,380 it's a whole pattern or picture, 510 00:25:01,380 --> 00:25:03,810 and it often requires much clinical experience 511 00:25:03,810 --> 00:25:06,450 with patients who have anomalies and their families. 512 00:25:06,450 --> 00:25:09,670 So for an example that I would give personally is that 513 00:25:10,590 --> 00:25:14,580 if a patient comes for developmental delay 514 00:25:14,580 --> 00:25:17,100 to see me in clinic, I can open up the door, 515 00:25:17,100 --> 00:25:19,237 see the 2-year-old and say, 516 00:25:19,237 --> 00:25:21,750 "That patient has Williams syndrome," 517 00:25:21,750 --> 00:25:25,530 because the gestalt, to me, is very characteristic 518 00:25:25,530 --> 00:25:27,270 without me going through and listing 519 00:25:27,270 --> 00:25:31,653 each of the dysmorphic features that that patient may have. 520 00:25:32,490 --> 00:25:33,323 All right. 521 00:25:35,100 --> 00:25:37,620 If you work in a newborn nursery a lot, 522 00:25:37,620 --> 00:25:41,070 you will eventually get a really good gestalt feeling 523 00:25:41,070 --> 00:25:42,900 for Down syndrome. 524 00:25:42,900 --> 00:25:44,430 The gestalt isn't always accurate, 525 00:25:44,430 --> 00:25:47,430 which is why it's helpful to have a systematic way 526 00:25:47,430 --> 00:25:49,860 to assess the individual features 527 00:25:49,860 --> 00:25:53,310 and convince yourself that you're feeling from the gestalt 528 00:25:53,310 --> 00:25:58,230 is actually confirmed by looking at the feature set 529 00:25:58,230 --> 00:26:00,573 that's expected for that syndrome. 530 00:26:03,210 --> 00:26:05,880 Fetal Alcohol Spectrum Disorder 531 00:26:05,880 --> 00:26:07,410 is a 532 00:26:07,410 --> 00:26:09,300 spectrum, as indicated, 533 00:26:09,300 --> 00:26:10,390 that is 534 00:26:11,340 --> 00:26:13,740 a teratogenic syndrome. 535 00:26:13,740 --> 00:26:18,300 So that means a teratogen is a substance which is toxic 536 00:26:18,300 --> 00:26:20,370 in the fetal period. 537 00:26:20,370 --> 00:26:23,610 So substances such as alcohol 538 00:26:23,610 --> 00:26:26,880 can alter the development and cause a birth defect 539 00:26:26,880 --> 00:26:29,430 or a set of birth defects. 540 00:26:29,430 --> 00:26:31,260 The birth defects that you see 541 00:26:31,260 --> 00:26:33,570 may depend on 542 00:26:33,570 --> 00:26:36,400 what gestational age that teratogen 543 00:26:38,484 --> 00:26:39,990 was present 544 00:26:39,990 --> 00:26:43,380 and what pattern of 545 00:26:43,380 --> 00:26:45,300 teratogen exposure there was. 546 00:26:45,300 --> 00:26:49,110 So was it a low level of alcohol exposure every day 547 00:26:49,110 --> 00:26:50,553 or was it a high level? 548 00:26:52,590 --> 00:26:56,340 Periodically those may change 549 00:26:56,340 --> 00:26:59,073 the impact of those teratogens on the development. 550 00:27:00,570 --> 00:27:03,720 Maternal and fetal genes related to alcohol metabolism 551 00:27:03,720 --> 00:27:07,060 and clearance are probably implicated 552 00:27:09,270 --> 00:27:10,680 in whether or not 553 00:27:10,680 --> 00:27:13,680 Fetal Alcohol Spectrum Disorder comes together 554 00:27:13,680 --> 00:27:15,090 but 555 00:27:15,090 --> 00:27:20,090 the primary inciting factor is the alcohol teratogen. 556 00:27:20,520 --> 00:27:21,353 All right. 557 00:27:21,353 --> 00:27:24,570 Here's a picture of a person with features 558 00:27:24,570 --> 00:27:26,520 of Fetal Alcohol Syndrome, 559 00:27:26,520 --> 00:27:28,600 and on the left there's a 560 00:27:30,510 --> 00:27:33,840 listing of the individual dysmorphic features. 561 00:27:33,840 --> 00:27:35,673 So a small head, microcephaly, 562 00:27:36,840 --> 00:27:38,610 epicanthal folds, 563 00:27:38,610 --> 00:27:40,020 which we're gonna go through in more detail, 564 00:27:40,020 --> 00:27:43,020 a low-nasal bridge, small eye openings, 565 00:27:43,020 --> 00:27:45,240 which means the measurement 566 00:27:45,240 --> 00:27:48,360 from the inner to the outer canthus, 567 00:27:48,360 --> 00:27:51,240 from here to here, 568 00:27:51,240 --> 00:27:53,763 is shorter than usual. 569 00:27:54,960 --> 00:27:57,093 We call that short palpebral fissures. 570 00:27:58,230 --> 00:28:00,753 A shorter, upturned nose, 571 00:28:01,680 --> 00:28:03,183 a flatter midface, 572 00:28:03,183 --> 00:28:07,887 so the zygomatic arches here tend to be less prominent. 573 00:28:09,090 --> 00:28:11,010 The philtrum, 574 00:28:11,010 --> 00:28:12,840 which is that 575 00:28:12,840 --> 00:28:14,490 patch of 576 00:28:14,490 --> 00:28:19,410 skin between the base of the septum, the nasal septum, 577 00:28:19,410 --> 00:28:23,133 and the top of the upper lip is smooth. 578 00:28:24,180 --> 00:28:25,770 So in most people, 579 00:28:25,770 --> 00:28:28,500 if you drive from one corner of the mouth, 580 00:28:28,500 --> 00:28:29,700 and you drive up a little bit, 581 00:28:29,700 --> 00:28:31,260 and you drive over, you go over a little hill, 582 00:28:31,260 --> 00:28:32,190 and then you're in a little valley, 583 00:28:32,190 --> 00:28:33,150 and you go over another hill, 584 00:28:33,150 --> 00:28:35,940 and then you're back sliding down the outer slope 585 00:28:35,940 --> 00:28:37,680 to the outer edge. 586 00:28:37,680 --> 00:28:40,053 So people with a smooth philtrum, 587 00:28:41,627 --> 00:28:44,850 it's more like a gentle rise or a flat desert 588 00:28:44,850 --> 00:28:46,983 as you take that road trip. 589 00:28:47,910 --> 00:28:50,580 So the last feature is a thin upper lip, 590 00:28:50,580 --> 00:28:54,090 or a thin upper vermilion border, 591 00:28:54,090 --> 00:28:55,680 narrow upper vermilion border. 592 00:28:55,680 --> 00:28:57,630 Vermilion is a color 593 00:28:57,630 --> 00:29:00,393 which people think refers to the color of the lips. 594 00:29:02,460 --> 00:29:05,640 So that vermilion border is 595 00:29:05,640 --> 00:29:08,220 what's in between the skin on the outside 596 00:29:08,220 --> 00:29:10,140 and the mucus membrane on the inside. 597 00:29:10,140 --> 00:29:13,860 And if that is thin then you have a thin upper lip. 598 00:29:13,860 --> 00:29:16,020 And then some degree of micrognathia, 599 00:29:16,020 --> 00:29:17,040 or undeveloped jaw. 600 00:29:17,040 --> 00:29:19,050 Here's another picture down here 601 00:29:19,050 --> 00:29:22,590 of an individual with a thin vermilion border. 602 00:29:22,590 --> 00:29:26,037 This person doesn't have so much of a smooth philtrum, 603 00:29:26,037 --> 00:29:29,320 and you can see that going over the two humps 604 00:29:30,340 --> 00:29:32,853 of the mountains or the camel there. 605 00:29:34,800 --> 00:29:35,633 All right. 606 00:29:35,633 --> 00:29:37,050 Our genetic assessment. 607 00:29:37,050 --> 00:29:40,170 We looking, again, for head-to-toe pattern. 608 00:29:40,170 --> 00:29:42,450 We have a standard physical assessment procedure. 609 00:29:42,450 --> 00:29:45,040 I have a fairly standard exam 610 00:29:46,170 --> 00:29:47,003 procedure. 611 00:29:48,120 --> 00:29:51,210 We screen for the presence of major and minor anomalies. 612 00:29:51,210 --> 00:29:52,470 These inform our decisions 613 00:29:52,470 --> 00:29:54,370 for referral to genetics professionals 614 00:29:55,470 --> 00:29:57,210 or preliminary testing. 615 00:29:57,210 --> 00:29:59,370 We consider the context of the family, 616 00:29:59,370 --> 00:30:00,900 consider the behavioral profile 617 00:30:00,900 --> 00:30:03,963 and consider the timeline of feature and development. 618 00:30:04,860 --> 00:30:05,820 Cognitive impairment. 619 00:30:05,820 --> 00:30:07,980 And I touched on this in the first slide. 620 00:30:07,980 --> 00:30:11,133 So a major reason for evaluation by genetics professional. 621 00:30:12,330 --> 00:30:13,620 This says more than 500, 622 00:30:13,620 --> 00:30:16,140 but it's probably a lot more than that, 623 00:30:16,140 --> 00:30:18,150 can cause cognitive impairment. 624 00:30:18,150 --> 00:30:21,453 In early childhood, we see that as developmental delay. 625 00:30:24,300 --> 00:30:25,470 So 626 00:30:25,470 --> 00:30:29,910 a lot of our evaluations are on 627 00:30:29,910 --> 00:30:32,710 infants, toddlers and children with developmental delay. 628 00:30:35,100 --> 00:30:37,230 This is considered a major anomaly. 629 00:30:37,230 --> 00:30:39,180 It can be syndromic or non-syndromic, 630 00:30:39,180 --> 00:30:40,870 meaning that 631 00:30:42,000 --> 00:30:45,180 a non-syndromic cognitive impairment disorder 632 00:30:45,180 --> 00:30:47,640 may not have facial features that are different, 633 00:30:47,640 --> 00:30:50,490 may not have digital features that are different, 634 00:30:50,490 --> 00:30:51,900 may not have anything on the outside 635 00:30:51,900 --> 00:30:53,790 that strikes you as different 636 00:30:53,790 --> 00:30:55,503 or strikes you with a gestalt, 637 00:30:57,835 --> 00:31:00,090 and so that may also be 638 00:31:00,090 --> 00:31:02,283 a genetic disorder. 639 00:31:03,720 --> 00:31:05,740 I'll mention here also 640 00:31:08,426 --> 00:31:09,720 the 641 00:31:09,720 --> 00:31:12,360 conflating factor of 642 00:31:12,360 --> 00:31:13,193 different 643 00:31:15,930 --> 00:31:17,190 characteristic features 644 00:31:17,190 --> 00:31:20,100 of different ethnic backgrounds and races. 645 00:31:20,100 --> 00:31:22,770 So those are things that one needs to be 646 00:31:22,770 --> 00:31:25,560 aware of and intuned to. 647 00:31:25,560 --> 00:31:28,050 This is really about learning about diversity. 648 00:31:28,050 --> 00:31:30,900 What does somebody from Nigeria really look like 649 00:31:30,900 --> 00:31:34,890 and how is that different in a normal context than others? 650 00:31:34,890 --> 00:31:39,180 And to try to subtract that from your assessment 651 00:31:39,180 --> 00:31:41,970 of dysmorphic features and patterns 652 00:31:41,970 --> 00:31:45,303 as you're going through your assessment. 653 00:31:47,340 --> 00:31:48,750 Getting back to cognitive impairment. 654 00:31:48,750 --> 00:31:51,510 Here's a list from the book, table 9-1, 655 00:31:51,510 --> 00:31:53,370 of a number of syndromes 656 00:31:53,370 --> 00:31:55,650 which can cause cognitive impairment, 657 00:31:55,650 --> 00:31:57,550 and I won't go through them in detail. 658 00:31:59,010 --> 00:31:59,843 Measurement. 659 00:31:59,843 --> 00:32:03,240 So qualitative descriptions make comparisons over time 660 00:32:03,240 --> 00:32:05,910 and between clinicians difficult. 661 00:32:05,910 --> 00:32:09,210 So sometimes we say 662 00:32:09,210 --> 00:32:11,550 let's look at the physical measurements 663 00:32:11,550 --> 00:32:14,280 and compare them to 664 00:32:14,280 --> 00:32:15,990 standard measurements, 665 00:32:15,990 --> 00:32:17,620 that is measurements of 666 00:32:19,110 --> 00:32:22,050 what is the mean, what's the standard deviation, 667 00:32:22,050 --> 00:32:23,400 so these bell curves 668 00:32:23,400 --> 00:32:26,580 or things that you will recognized from your training 669 00:32:26,580 --> 00:32:28,440 as, like, growth charts, okay? 670 00:32:28,440 --> 00:32:31,110 Similar kinds of charts for physical measurements 671 00:32:31,110 --> 00:32:36,030 that help us identify body parts that are out of range, 672 00:32:36,030 --> 00:32:40,560 out of expected range for their positions or sizes. 673 00:32:40,560 --> 00:32:43,140 So, classically, we look at the eye. 674 00:32:43,140 --> 00:32:46,620 I talked about hypertelorism early in this lecture, 675 00:32:46,620 --> 00:32:47,550 wide-spaced eyes. 676 00:32:47,550 --> 00:32:48,570 That's C here. 677 00:32:48,570 --> 00:32:52,050 You measure the distance between the center of the pupils. 678 00:32:52,050 --> 00:32:53,170 I like to use 679 00:32:54,590 --> 00:32:57,480 a clear, plastic ruler, one that's flexible, 680 00:32:57,480 --> 00:32:59,880 without sharp points and stuff so that children, 681 00:33:01,620 --> 00:33:03,470 they can see through it a little bit, 682 00:33:06,630 --> 00:33:10,803 and they're moving around or unlikely to result in a injury. 683 00:33:12,150 --> 00:33:15,060 So you measure the distance between the pupils, 684 00:33:15,060 --> 00:33:17,340 or interpupillary distance, 685 00:33:17,340 --> 00:33:19,450 the distance between the inner canthi 686 00:33:20,490 --> 00:33:25,490 or an inner, I-N-N-E-R, canthal distance. 687 00:33:25,920 --> 00:33:27,987 You measure the distance between the outer canthi, 688 00:33:27,987 --> 00:33:30,190 you try to estimate 'cause sometimes 689 00:33:31,230 --> 00:33:32,820 the eyelashes get in the way, 690 00:33:32,820 --> 00:33:35,400 so you try to estimate where 691 00:33:35,400 --> 00:33:39,210 those two skin pieces come together 692 00:33:39,210 --> 00:33:41,280 to form the outer canthus. 693 00:33:41,280 --> 00:33:43,110 And then measuring the philtrum, 694 00:33:43,110 --> 00:33:46,330 which is from the base of the nose to the 695 00:33:47,370 --> 00:33:50,100 edge of the upper vermilion border. 696 00:33:50,100 --> 00:33:51,630 Okay? 697 00:33:51,630 --> 00:33:53,670 And then I put over here the ear length as well. 698 00:33:53,670 --> 00:33:55,600 The ears are measured 699 00:33:57,210 --> 00:34:00,720 on their longest axis, which goes from the tip of the lobe 700 00:34:00,720 --> 00:34:03,330 to the upper edge of the helix. 701 00:34:03,330 --> 00:34:06,690 And there are tables with 702 00:34:06,690 --> 00:34:09,660 standard curves against the same, like, growth curves, 703 00:34:09,660 --> 00:34:10,810 you know, against age 704 00:34:11,820 --> 00:34:15,660 that are in some of the classic genetic books. 705 00:34:15,660 --> 00:34:17,943 And you can find them online as well. 706 00:34:19,860 --> 00:34:21,330 Variations in height and weight, 707 00:34:21,330 --> 00:34:22,163 the patient's height and weight 708 00:34:22,163 --> 00:34:24,240 in the range normal for thier age 709 00:34:24,240 --> 00:34:25,950 inconsistent with those of family members. 710 00:34:25,950 --> 00:34:28,110 So we look at mid-parental age, 711 00:34:28,110 --> 00:34:29,650 excuse me, mid-parental height 712 00:34:30,900 --> 00:34:32,430 and look at the percentile for that, 713 00:34:32,430 --> 00:34:36,837 and say, "Is he running above or below expected height?" 714 00:34:39,229 --> 00:34:40,680 And we look at that on normal growth curves. 715 00:34:40,680 --> 00:34:43,590 Some disorders will have their own growth curves. 716 00:34:43,590 --> 00:34:45,450 You can look at the height and weight 717 00:34:45,450 --> 00:34:46,683 on those growth curves. 718 00:34:48,060 --> 00:34:49,100 Prader-Willi Syndrome 719 00:34:49,100 --> 00:34:52,860 is an example of a syndrome with variant growth. 720 00:34:52,860 --> 00:34:56,280 It includes increased body weight due to hyperphasia. 721 00:34:56,280 --> 00:34:59,160 They, basically, don't 722 00:34:59,160 --> 00:35:01,140 have a sensation of satiety, 723 00:35:01,140 --> 00:35:03,183 or being satisfied after eating. 724 00:35:04,440 --> 00:35:06,210 And that characteristic starts around 725 00:35:06,210 --> 00:35:07,860 two to four years of age. 726 00:35:07,860 --> 00:35:11,430 If you see increased body weight occurring well before that, 727 00:35:11,430 --> 00:35:13,140 probably not Prader-Willi Syndrome 728 00:35:13,140 --> 00:35:15,690 because, in fact, in infancy 729 00:35:15,690 --> 00:35:18,063 Prader-Willi Syndrome has a low body weight, 730 00:35:19,360 --> 00:35:21,300 they have a lot of feeding difficulties. 731 00:35:21,300 --> 00:35:23,160 They're scrawny, little kids, 732 00:35:23,160 --> 00:35:26,210 and they have generalized hypotonia, 733 00:35:26,210 --> 00:35:28,530 or low muscle tone. 734 00:35:28,530 --> 00:35:32,430 So another pattern that you can recognize in early infancy. 735 00:35:32,430 --> 00:35:37,430 So chronic feeding difficulties and significant hypotonia, 736 00:35:37,470 --> 00:35:38,527 you might ask the question, 737 00:35:38,527 --> 00:35:41,520 "Does this child have Prader-Willi Syndrome?" 738 00:35:41,520 --> 00:35:42,353 All right. 739 00:35:42,353 --> 00:35:45,510 Genetic diseases with stature variations. 740 00:35:45,510 --> 00:35:46,343 Two 741 00:35:47,340 --> 00:35:48,173 extremes. 742 00:35:48,173 --> 00:35:52,170 One is achondroplasia, which has very short stature. 743 00:35:52,170 --> 00:35:56,340 You've noticed people on television, actors 744 00:35:56,340 --> 00:36:00,570 and families with achondroplasia, mid-face hypoplasia, 745 00:36:00,570 --> 00:36:02,130 frontal bossing, short limbs. 746 00:36:02,130 --> 00:36:03,930 Marfan syndrome 747 00:36:03,930 --> 00:36:08,190 actually causes the long bones to grow longer. 748 00:36:08,190 --> 00:36:10,680 So they have tall stature, long limbs, 749 00:36:10,680 --> 00:36:13,590 and it's considered a connective tissue disorder 750 00:36:13,590 --> 00:36:14,423 with additional 751 00:36:15,690 --> 00:36:17,130 clinical risks. 752 00:36:17,130 --> 00:36:18,870 So both of these are things 753 00:36:18,870 --> 00:36:22,600 you can Google images on the internet and 754 00:36:23,850 --> 00:36:25,593 find examples of that. 755 00:36:27,480 --> 00:36:29,760 Dysmorphic features of the skull 756 00:36:29,760 --> 00:36:32,913 fits into the general category of craniofacial anomalies. 757 00:36:33,870 --> 00:36:37,350 Plagiocephaly is a significant asymmetry of the skull. 758 00:36:37,350 --> 00:36:39,540 These first four pictures here on the right, 759 00:36:39,540 --> 00:36:40,710 if you're looking from the top, 760 00:36:40,710 --> 00:36:44,850 it often helps to look from the top to see what's going on. 761 00:36:44,850 --> 00:36:47,790 And there is not a nice symmetric oval. 762 00:36:47,790 --> 00:36:49,650 So there's an asymmetry here. 763 00:36:49,650 --> 00:36:51,660 It can be due to positional effects 764 00:36:51,660 --> 00:36:55,500 or it can be due to premature 765 00:36:55,500 --> 00:36:58,590 closure of some of the sutures 766 00:36:58,590 --> 00:36:59,760 in 767 00:36:59,760 --> 00:37:01,350 the skull. 768 00:37:01,350 --> 00:37:05,340 Craniosynostosis is premature closure of those sutures, 769 00:37:05,340 --> 00:37:06,870 and it happens early enough 770 00:37:06,870 --> 00:37:09,870 you may get a rather dramatic shift 771 00:37:09,870 --> 00:37:13,620 in the direction of growth of the skull 772 00:37:13,620 --> 00:37:16,200 because the brain is still growing underneath it, 773 00:37:16,200 --> 00:37:18,570 and the skull needs to grow, 774 00:37:18,570 --> 00:37:21,420 but if it's unable to grow in one direction 775 00:37:21,420 --> 00:37:24,030 because that suture has already fused, 776 00:37:24,030 --> 00:37:24,863 then you 777 00:37:25,985 --> 00:37:26,818 get this. 778 00:37:26,818 --> 00:37:28,470 If you fuse a bunch of sutures, 779 00:37:28,470 --> 00:37:31,380 then you can restrict brain growth, 780 00:37:31,380 --> 00:37:33,180 get increased intracranial pressure, 781 00:37:33,180 --> 00:37:34,710 and that's a bad thing. 782 00:37:34,710 --> 00:37:37,050 You need to pick that up early. 783 00:37:37,050 --> 00:37:39,870 Scalp defects, aplasia cutis congenital, 784 00:37:39,870 --> 00:37:44,010 which basically means you were born with a spot on your skin 785 00:37:44,010 --> 00:37:48,060 that either didn't form or formed very poorly. 786 00:37:48,060 --> 00:37:49,320 It's often on the scalp, 787 00:37:49,320 --> 00:37:52,710 but you can have more complex forms of this. 788 00:37:52,710 --> 00:37:55,110 And it's usually a single scalp lesion 789 00:37:55,110 --> 00:37:57,510 that looks like a punched out region 790 00:37:57,510 --> 00:38:01,020 with a very, very thin, almost translucent 791 00:38:01,020 --> 00:38:03,360 or scar-like 792 00:38:03,360 --> 00:38:06,630 tissue in it because it, basically, didn't form 793 00:38:06,630 --> 00:38:07,683 normal skin there. 794 00:38:09,053 --> 00:38:11,280 It can be very small to very large. 795 00:38:11,280 --> 00:38:15,090 Sometimes you have to dig through the scalp to find it. 796 00:38:15,090 --> 00:38:16,950 I don't mean dig, I mean just, you know, 797 00:38:16,950 --> 00:38:19,440 part the hair to look for it. 798 00:38:19,440 --> 00:38:21,300 It may heal before birth 799 00:38:21,300 --> 00:38:25,800 but it's still going to have this parchment-like skin 800 00:38:25,800 --> 00:38:28,023 or scar or absent skin. 801 00:38:28,860 --> 00:38:30,720 And there's typically no hair 802 00:38:30,720 --> 00:38:33,963 in this little circumscribed, punched out area. 803 00:38:35,280 --> 00:38:38,220 And you can Google that online as well. 804 00:38:38,220 --> 00:38:41,160 So I can't put pictures up for everything 805 00:38:41,160 --> 00:38:45,030 because I can't guarantee that they're royalty-free 806 00:38:45,030 --> 00:38:46,290 if I just find them on the internet. 807 00:38:46,290 --> 00:38:49,500 But you can go look on the internet and find them. 808 00:38:49,500 --> 00:38:50,333 Okay. 809 00:38:50,333 --> 00:38:52,263 Macrocephaly is an enlarged head, 810 00:38:53,580 --> 00:38:55,380 and it 811 00:38:55,380 --> 00:38:56,880 is 812 00:38:56,880 --> 00:38:58,020 a head circumference, 813 00:38:58,020 --> 00:39:00,060 or occipital frontal circumference 814 00:39:00,060 --> 00:39:03,900 greater than 97th percentile for the same age and gender. 815 00:39:03,900 --> 00:39:05,340 So there are charts for boys and girls, 816 00:39:05,340 --> 00:39:07,560 same as height and weight. 817 00:39:07,560 --> 00:39:09,180 And we measure from the frontal region, 818 00:39:09,180 --> 00:39:10,980 just above the eyebrow ridge 819 00:39:10,980 --> 00:39:14,220 to an area near the top of the occipital bone. 820 00:39:14,220 --> 00:39:16,380 And really, you know, when I measure 821 00:39:16,380 --> 00:39:19,140 because different patients have different head shapes, 822 00:39:19,140 --> 00:39:20,550 I, basically, am measuring 823 00:39:20,550 --> 00:39:24,960 the largest front-to-back circumference of the head. 824 00:39:24,960 --> 00:39:27,420 So I put the measuring tape around the head 825 00:39:27,420 --> 00:39:29,490 and I scoot it up and down 826 00:39:29,490 --> 00:39:33,660 until it pulls out to the level that is the maximum. 827 00:39:33,660 --> 00:39:36,840 And that's what I use for my measurement. 828 00:39:36,840 --> 00:39:38,973 Microcephaly is the opposite, small head, 829 00:39:39,810 --> 00:39:42,000 head circumference that's more than two standard deviations 830 00:39:42,000 --> 00:39:44,050 below what's expected for age and gender. 831 00:39:46,020 --> 00:39:49,590 This is a picture from the book-generated slides. 832 00:39:49,590 --> 00:39:50,550 It doesn't have text with it, 833 00:39:50,550 --> 00:39:51,660 so I'm not sure why it's here, 834 00:39:51,660 --> 00:39:54,870 but there are dysmorphic features here. 835 00:39:54,870 --> 00:39:57,070 I will point out while you're looking at it, 836 00:39:58,890 --> 00:40:00,210 that 837 00:40:00,210 --> 00:40:04,140 there's a wider gap between the first and second toes. 838 00:40:04,140 --> 00:40:06,060 We call that a sandal gap. 839 00:40:06,060 --> 00:40:07,080 And then there's something different 840 00:40:07,080 --> 00:40:10,530 about the second and third toes on both sides, 841 00:40:10,530 --> 00:40:13,950 which is that they're lacking the space between them 842 00:40:13,950 --> 00:40:15,240 at the proximal ends, 843 00:40:15,240 --> 00:40:18,527 and we call this partial cutaneous syndactyly 844 00:40:18,527 --> 00:40:21,120 'cause it doesn't look like the bones are actually joined, 845 00:40:21,120 --> 00:40:23,070 it's just the skin. 846 00:40:23,070 --> 00:40:25,410 And there's another term 847 00:40:25,410 --> 00:40:28,290 that this goes by, which is zygodactyly, 848 00:40:28,290 --> 00:40:29,970 or brothers, 849 00:40:29,970 --> 00:40:31,980 think digits that are brothers. 850 00:40:31,980 --> 00:40:34,800 And when they're in this two-three position, 851 00:40:34,800 --> 00:40:38,460 a little bit of zygodactyly can be a familial trait. 852 00:40:38,460 --> 00:40:42,000 More of it in the context of, say, 853 00:40:42,000 --> 00:40:46,440 a long philtrum, short upturned nose, 854 00:40:46,440 --> 00:40:49,170 cleft palate would really point you 855 00:40:49,170 --> 00:40:52,500 toward a disorder of cholesterol metabolism 856 00:40:52,500 --> 00:40:54,783 called Smith-Lemli-Opitz syndrome. 857 00:40:56,520 --> 00:40:58,440 Coarse features is something else 858 00:40:58,440 --> 00:41:03,420 that's a subjective thing that we often talk about. 859 00:41:03,420 --> 00:41:06,450 The book uses this picture on the left for coarse features. 860 00:41:06,450 --> 00:41:08,910 There's somewhat fuller lips, 861 00:41:08,910 --> 00:41:11,040 a sense that the mouth isn't closing all the way, 862 00:41:11,040 --> 00:41:13,470 maybe a larger tongue. 863 00:41:13,470 --> 00:41:16,803 This person also has up-slanting palpebral fissures, 864 00:41:18,120 --> 00:41:18,953 and 865 00:41:20,164 --> 00:41:22,290 a little bit of a prominent 866 00:41:22,290 --> 00:41:23,760 eyebrows. 867 00:41:23,760 --> 00:41:26,460 These kids have other disorders 868 00:41:26,460 --> 00:41:28,590 which are really characterized 869 00:41:28,590 --> 00:41:30,900 by the coarseness of their features. 870 00:41:30,900 --> 00:41:31,780 So 871 00:41:33,262 --> 00:41:34,143 thick lips, 872 00:41:35,640 --> 00:41:39,570 exaggerated creases, thick, bushy eyebrows 873 00:41:39,570 --> 00:41:41,073 and prominent brows. 874 00:41:42,240 --> 00:41:45,360 Here there's some little differences in the ears as well. 875 00:41:45,360 --> 00:41:48,810 So coarse is one of those gestalt feelings 876 00:41:48,810 --> 00:41:50,340 that 877 00:41:50,340 --> 00:41:53,280 you need to work with for a while 878 00:41:53,280 --> 00:41:54,810 before completely understanding. 879 00:41:54,810 --> 00:41:56,550 When we think about coarse, 880 00:41:56,550 --> 00:41:59,580 it's one of those trigger words to think about 881 00:41:59,580 --> 00:42:02,160 lysosomal storage diseases. 882 00:42:02,160 --> 00:42:02,993 So 883 00:42:04,140 --> 00:42:05,640 philtrum is, again, that space 884 00:42:05,640 --> 00:42:06,960 between the bottom of the lip, 885 00:42:06,960 --> 00:42:07,793 I mean, I'm sorry, 886 00:42:07,793 --> 00:42:10,200 the top of the lip and the bottom of the nose. 887 00:42:10,200 --> 00:42:12,000 Its length can vary. 888 00:42:12,000 --> 00:42:16,233 Smooth philtrum is seen in Fetal Alcohol Spectrum Disorder. 889 00:42:17,190 --> 00:42:19,230 It's important that the smoothness is assessed 890 00:42:19,230 --> 00:42:21,480 when the person is not smiling 891 00:42:21,480 --> 00:42:24,180 because smiling flattens out your philtrum. 892 00:42:24,180 --> 00:42:26,580 So in the top picture here on the left, 893 00:42:26,580 --> 00:42:29,280 this child really has a smooth philtrum, 894 00:42:29,280 --> 00:42:30,603 has a long philtrum. 895 00:42:31,560 --> 00:42:35,010 This person in the middle is not smiling, 896 00:42:35,010 --> 00:42:37,560 and you can see they have their little camel's-hump 897 00:42:39,120 --> 00:42:40,410 trajectory there. 898 00:42:40,410 --> 00:42:43,050 But that same person, when they smile, 899 00:42:43,050 --> 00:42:44,190 it looks quite smooth. 900 00:42:44,190 --> 00:42:48,420 So you need to look at them in the un-smiling position. 901 00:42:48,420 --> 00:42:50,340 Doesn't necessarily mean there's a genetic disorder, 902 00:42:50,340 --> 00:42:52,410 again, it's one feature 903 00:42:52,410 --> 00:42:56,430 that is not important in and of itself, 904 00:42:56,430 --> 00:42:58,560 and we're looking for a pattern. 905 00:42:58,560 --> 00:42:59,670 And that's actually helpful, 906 00:42:59,670 --> 00:43:00,960 when you're looking at these features 907 00:43:00,960 --> 00:43:02,550 and commenting on them, 908 00:43:02,550 --> 00:43:05,250 to talk to the patient and the parent 909 00:43:05,250 --> 00:43:06,420 so that they don't feel like 910 00:43:06,420 --> 00:43:10,323 that every little thing that you're identifying is bad. 911 00:43:12,930 --> 00:43:14,340 Okay. 912 00:43:14,340 --> 00:43:18,210 We went over the Fetal Alcohol Syndrome features before. 913 00:43:18,210 --> 00:43:19,080 There's 914 00:43:19,080 --> 00:43:23,490 a diagnostic criteria set for Fetal Alcohol Syndrome, 915 00:43:23,490 --> 00:43:24,720 for fetal alcohol effects 916 00:43:24,720 --> 00:43:27,180 and for Fetal Alcohol Spectrum Disorder, 917 00:43:27,180 --> 00:43:28,013 which are all 918 00:43:28,890 --> 00:43:31,800 from the most physically affected 919 00:43:31,800 --> 00:43:36,120 to the least physically affected with residual brain effects 920 00:43:36,120 --> 00:43:39,093 that may not be evident on the exterior. 921 00:43:40,800 --> 00:43:42,510 Okay, what about the spacing of the eyes? 922 00:43:42,510 --> 00:43:44,340 So on the left here we see somebody 923 00:43:44,340 --> 00:43:46,440 with extreme hypotelorism. 924 00:43:46,440 --> 00:43:50,493 So small distance between the center of the eyeballs. 925 00:43:51,450 --> 00:43:53,507 And in the middle, there's normal spacing. 926 00:43:53,507 --> 00:43:56,340 And on the right side, there's a wide spacing. 927 00:43:56,340 --> 00:43:59,040 Now I've added a little white patch to this person's hair 928 00:43:59,040 --> 00:44:00,660 because, 929 00:44:00,660 --> 00:44:02,580 again, there's a gestalt here. 930 00:44:02,580 --> 00:44:06,510 If you see wide-spaced eyes and a white patch 931 00:44:06,510 --> 00:44:09,510 or maybe a partially blue iris 932 00:44:09,510 --> 00:44:12,720 or one iris blue and the other one brown, 933 00:44:12,720 --> 00:44:15,180 that's a gestalt for a disorder 934 00:44:15,180 --> 00:44:17,163 called Waardenburg syndrome. 935 00:44:18,579 --> 00:44:20,170 Okay? 936 00:44:20,170 --> 00:44:22,560 Palpebral fissures, we've talked about this a little bit. 937 00:44:22,560 --> 00:44:23,640 So here's an up-slanting. 938 00:44:23,640 --> 00:44:25,920 If you draw a line between the inner and out or canthus, 939 00:44:25,920 --> 00:44:27,210 it slants up. 940 00:44:27,210 --> 00:44:29,670 Here's a normal-slanting, 941 00:44:29,670 --> 00:44:31,680 so more or less horizontal. 942 00:44:31,680 --> 00:44:33,720 And then there's down-slanting, 943 00:44:33,720 --> 00:44:37,773 going from upper to lower from inward to outward. 944 00:44:39,450 --> 00:44:41,520 Prominent epicanthal folds. 945 00:44:41,520 --> 00:44:44,040 And the epicanthus is a fold of skin 946 00:44:44,040 --> 00:44:47,370 that overlies the inner canthus. 947 00:44:47,370 --> 00:44:49,680 That's what epicanthus means. 948 00:44:49,680 --> 00:44:51,930 It's a vertical fold of tissue 949 00:44:51,930 --> 00:44:54,060 that lies between the eye and the nose. 950 00:44:54,060 --> 00:44:57,000 And it may be a normal variation in people of Asian descent. 951 00:44:57,000 --> 00:45:01,020 So, again, on your normal patients, keep an eye on this, 952 00:45:01,020 --> 00:45:02,880 and try to learn what's normal 953 00:45:02,880 --> 00:45:05,370 in different ethnic backgrounds 954 00:45:05,370 --> 00:45:10,260 because that will help you recognize what is not normal 955 00:45:10,260 --> 00:45:12,843 in both those ethnic backgrounds and others. 956 00:45:14,340 --> 00:45:16,170 It's seen in a number of genetic disorders, 957 00:45:16,170 --> 00:45:17,610 but it's really not quite the same. 958 00:45:17,610 --> 00:45:20,190 That's why you need to look at them a lot, 959 00:45:20,190 --> 00:45:22,320 and it may obscure the inner canthus. 960 00:45:22,320 --> 00:45:24,840 So I've put a little thing on here to say, 961 00:45:24,840 --> 00:45:27,120 you know, here's a fold that you might see 962 00:45:27,120 --> 00:45:29,280 in Down syndrome, for example, 963 00:45:29,280 --> 00:45:30,400 an epicanthal fold 964 00:45:31,380 --> 00:45:35,133 that obscures that inner corner of the eye. 965 00:45:35,970 --> 00:45:37,530 Okay? 966 00:45:37,530 --> 00:45:39,450 Measuring to see if the ears are low set. 967 00:45:39,450 --> 00:45:41,040 I mentioned that earlier, 968 00:45:41,040 --> 00:45:44,103 and so I won't spend a lot of time on that. 969 00:45:46,680 --> 00:45:49,390 Cleft lip with or without cleft palate 970 00:45:50,370 --> 00:45:53,190 is a complex process and growth inhibited, 971 00:45:53,190 --> 00:45:54,730 a gap may result 972 00:45:55,620 --> 00:45:59,220 either through programmatic or obstruction 973 00:45:59,220 --> 00:46:02,310 deformation-kinds of terms. 974 00:46:02,310 --> 00:46:04,500 And it can be caused by genetics 975 00:46:04,500 --> 00:46:06,723 or environmental factors during pregnancy. 976 00:46:08,040 --> 00:46:11,640 Lip pits are symmetrical depressions 977 00:46:11,640 --> 00:46:13,590 usually in the part of the lower lip called the vermilion, 978 00:46:13,590 --> 00:46:15,480 again, that red part of the lip 979 00:46:15,480 --> 00:46:18,180 between the skin and the mucus membrane. 980 00:46:18,180 --> 00:46:23,180 And here, down here, are one, two, they're quite symmetric. 981 00:46:23,700 --> 00:46:25,860 And those are 982 00:46:25,860 --> 00:46:28,170 a feature that's almost diagnostic of a disorder 983 00:46:28,170 --> 00:46:29,823 called Van der Woude syndrome. 984 00:46:30,870 --> 00:46:34,230 That's autosomal dominant, has very high penetrance 985 00:46:34,230 --> 00:46:35,853 but has variable expressivity. 986 00:46:38,430 --> 00:46:39,263 All right. 987 00:46:39,263 --> 00:46:40,740 Dysmorphia features of the hands and feet. 988 00:46:40,740 --> 00:46:42,843 Polydactyly is an extra digit. 989 00:46:44,010 --> 00:46:48,920 Sometimes a small extra digit might have been cut off or 990 00:46:50,520 --> 00:46:54,990 put in a tight ligature at birth and fallen off. 991 00:46:54,990 --> 00:46:58,560 So sometimes, if you look closely, 992 00:46:58,560 --> 00:47:02,260 there will be a little scar on the outer edge of 993 00:47:03,759 --> 00:47:08,250 the hand that will indicate that a digit was present there 994 00:47:08,250 --> 00:47:11,190 that the patient may not actually know was removed 995 00:47:11,190 --> 00:47:12,873 in the newborn period. 996 00:47:14,160 --> 00:47:15,880 So we divide 997 00:47:17,299 --> 00:47:19,500 the polydactyly into 998 00:47:19,500 --> 00:47:21,300 pre-axial 999 00:47:21,300 --> 00:47:23,520 and post-axial polydactyly. 1000 00:47:23,520 --> 00:47:25,290 So what's pre and post? 1001 00:47:25,290 --> 00:47:28,560 So we look at this sailor over here, 1002 00:47:28,560 --> 00:47:29,790 he's standing at attention, 1003 00:47:29,790 --> 00:47:31,590 and his hands are at his sides, 1004 00:47:31,590 --> 00:47:33,090 and his thumb is pointing forward, 1005 00:47:33,090 --> 00:47:35,130 and his little finger is pointing backward. 1006 00:47:35,130 --> 00:47:36,390 So there's an axis. 1007 00:47:36,390 --> 00:47:39,060 So, you know, the middle plane of his body 1008 00:47:39,060 --> 00:47:42,060 between front and back, that's the axial, 1009 00:47:42,060 --> 00:47:44,580 that's the axis that we're talking about in axial. 1010 00:47:44,580 --> 00:47:46,860 So post-axial is behind that axis 1011 00:47:46,860 --> 00:47:49,020 and pre-axial is in front of that axis. 1012 00:47:49,020 --> 00:47:53,670 So if the extra digit is on the thumb side, it's pre-axial. 1013 00:47:53,670 --> 00:47:57,720 If the extra digit is on the pinky side, it's post-axial. 1014 00:47:57,720 --> 00:47:59,290 So in these pictures 1015 00:48:00,724 --> 00:48:03,930 the first panel on the left is pre-axial. 1016 00:48:03,930 --> 00:48:08,220 You've got two big toes on a single foot. 1017 00:48:08,220 --> 00:48:09,760 You've got a little bit of cutaneous syndactyly 1018 00:48:09,760 --> 00:48:11,613 or zygodactyly here. 1019 00:48:12,750 --> 00:48:13,770 And the same thing here. 1020 00:48:13,770 --> 00:48:14,603 You've got 1021 00:48:15,510 --> 00:48:17,310 more toes seemed to be added 1022 00:48:17,310 --> 00:48:19,773 on that inner surface of the foot. 1023 00:48:21,930 --> 00:48:25,290 Here's post-axial polydactyly in the hand, 1024 00:48:25,290 --> 00:48:27,210 where you have a normal looking thumb, 1025 00:48:27,210 --> 00:48:28,950 normal first, second, third, fourth fingers, 1026 00:48:28,950 --> 00:48:33,210 and there's an extra one here on the outside, 1027 00:48:33,210 --> 00:48:34,080 okay? 1028 00:48:34,080 --> 00:48:36,523 So that's post-axial polydactyly. 1029 00:48:37,627 --> 00:48:38,910 Why do we care? 1030 00:48:38,910 --> 00:48:41,610 Because different syndromes have different patterns, 1031 00:48:41,610 --> 00:48:43,980 predominantly pre-axial, predominantly post-axial, 1032 00:48:43,980 --> 00:48:45,210 sometimes both, 1033 00:48:45,210 --> 00:48:47,100 or pre-axial on the upper extremity 1034 00:48:47,100 --> 00:48:49,590 and post-axial on the lower extremity, for example. 1035 00:48:49,590 --> 00:48:50,423 So 1036 00:48:50,423 --> 00:48:52,110 it's a differentiating feature 1037 00:48:52,110 --> 00:48:53,463 that really does help us. 1038 00:48:54,360 --> 00:48:56,460 Other dysmorphic features of hands and feet. 1039 00:48:56,460 --> 00:48:58,923 Arachnodactyly, long, slender fingers. 1040 00:49:00,300 --> 00:49:01,590 Arachno means spider, 1041 00:49:01,590 --> 00:49:04,110 so this literally means spider fingers. 1042 00:49:04,110 --> 00:49:07,530 And there are some tricks or direct measurements you can do 1043 00:49:07,530 --> 00:49:10,120 to see whether you're gestalt 1044 00:49:11,640 --> 00:49:14,490 sense of that is true or not. 1045 00:49:14,490 --> 00:49:16,920 Brachydactyly, very short fingers, 1046 00:49:16,920 --> 00:49:20,100 sometimes extremely short as in this case, 1047 00:49:20,100 --> 00:49:21,330 or toes. 1048 00:49:21,330 --> 00:49:24,030 And then syndactyly is fused digits. 1049 00:49:24,030 --> 00:49:25,230 In this case 1050 00:49:25,230 --> 00:49:27,060 digits 2, 3, 4, 5, 1051 00:49:27,060 --> 00:49:31,320 so two through five are completely syndactylic, 1052 00:49:31,320 --> 00:49:32,403 fused together. 1053 00:49:33,390 --> 00:49:34,223 And 1054 00:49:35,507 --> 00:49:37,830 it looks like there's a bit of polydactyly here as well 1055 00:49:37,830 --> 00:49:38,663 on this one, 1056 00:49:38,663 --> 00:49:39,496 and a broad thumb. 1057 00:49:39,496 --> 00:49:42,000 So put that into your syndrome search, 1058 00:49:42,000 --> 00:49:44,100 and see what you come up with. 1059 00:49:44,100 --> 00:49:45,333 Fused digits. 1060 00:49:47,730 --> 00:49:50,550 Also you can have partial fusion. 1061 00:49:50,550 --> 00:49:55,410 So here's a patient who has webbing between the fingers, 1062 00:49:55,410 --> 00:50:00,410 and that can be considered partial cutaneous syndactyly. 1063 00:50:00,600 --> 00:50:01,620 This looks like the hand 1064 00:50:01,620 --> 00:50:03,210 of an individual with Aarskog Syndrome. 1065 00:50:03,210 --> 00:50:05,283 So that's something you can look up. 1066 00:50:06,780 --> 00:50:08,490 Dysmorphology of the joints, 1067 00:50:08,490 --> 00:50:11,580 greater or lower range of motion. 1068 00:50:11,580 --> 00:50:13,797 Hyper-mobility or hyper-extensibility 1069 00:50:13,797 --> 00:50:15,480 are the terms that we typically use. 1070 00:50:15,480 --> 00:50:16,830 We think of Ehlers-Danlos syndrome, 1071 00:50:16,830 --> 00:50:17,910 which is really 1072 00:50:17,910 --> 00:50:20,490 a large group of connective tissue disorders. 1073 00:50:20,490 --> 00:50:22,260 Some of them have fragile blood vessels. 1074 00:50:22,260 --> 00:50:25,380 We need to differentiate those from the ones that don't, 1075 00:50:25,380 --> 00:50:28,600 that just have hyper-mobility or hyper-extensibility 1076 00:50:29,520 --> 00:50:33,360 and soft, velvety and elastic skin, 1077 00:50:33,360 --> 00:50:34,740 hyper-mobility. 1078 00:50:34,740 --> 00:50:35,573 And then 1079 00:50:36,870 --> 00:50:38,670 it's important to recognize 1080 00:50:38,670 --> 00:50:41,040 that there are diagnostic criteria 1081 00:50:41,040 --> 00:50:43,170 for Ehlers-Danlos syndromes, 1082 00:50:43,170 --> 00:50:45,360 the different forms of Ehlers-Danlos syndromes, 1083 00:50:45,360 --> 00:50:46,990 and that not everybody with 1084 00:50:48,120 --> 00:50:50,120 the ability to pop a shoulder in and out 1085 00:50:51,000 --> 00:50:52,440 has Ehlers-Danlos syndrome. 1086 00:50:52,440 --> 00:50:55,057 We see a lot of individuals that we need to say, 1087 00:50:55,057 --> 00:50:56,970 "Yes, you may have some loose joints, 1088 00:50:56,970 --> 00:50:59,220 but you don't have Ehlers-Danlos syndrome." 1089 00:50:59,220 --> 00:51:00,450 And there's no genetic testing 1090 00:51:00,450 --> 00:51:03,180 for the hyper-mobility type anyway, 1091 00:51:03,180 --> 00:51:05,490 so we can't do any testing to, you know, 1092 00:51:05,490 --> 00:51:07,623 change what's going on here. 1093 00:51:08,970 --> 00:51:11,940 In 2017, 1094 00:51:11,940 --> 00:51:14,700 there was a international meeting 1095 00:51:14,700 --> 00:51:19,170 that culminated several years of experts working together 1096 00:51:19,170 --> 00:51:23,250 to tweak the international classification 1097 00:51:23,250 --> 00:51:25,320 of Ehlers-Danlos syndrome 1098 00:51:25,320 --> 00:51:29,433 and to create the diagnostic criteria for those. 1099 00:51:30,600 --> 00:51:33,780 So that's really what we work from these days. 1100 00:51:33,780 --> 00:51:36,780 And that's a really good resource to go by. 1101 00:51:36,780 --> 00:51:39,630 There's a whole issue of a journal that was addressed, 1102 00:51:39,630 --> 00:51:44,040 two articles that address Ehlers-Danlos syndrome 1103 00:51:44,040 --> 00:51:45,453 and its various types. 1104 00:51:46,470 --> 00:51:47,700 So we're nearing the end of the lecture, 1105 00:51:47,700 --> 00:51:51,690 and I just wanted to throw out another recommendation, 1106 00:51:51,690 --> 00:51:54,660 which is a book called "The Bedside Dysmorphologist". 1107 00:51:54,660 --> 00:51:59,190 It's a small book, you can have it on, you know, online 1108 00:51:59,190 --> 00:52:02,910 for about somewhere around $60. 1109 00:52:02,910 --> 00:52:04,770 It's in the second edition. 1110 00:52:04,770 --> 00:52:06,963 I bought the first edition actually, 1111 00:52:07,830 --> 00:52:09,240 and had it signed by Willie Reardon, 1112 00:52:09,240 --> 00:52:10,690 who is an old friend of mine. 1113 00:52:11,640 --> 00:52:15,240 And I haven't even actually looked at the second edition, 1114 00:52:15,240 --> 00:52:19,050 but I suspect it's even better than the first. 1115 00:52:19,050 --> 00:52:20,880 So what's nice about this book 1116 00:52:20,880 --> 00:52:24,330 is that it takes you through the process 1117 00:52:24,330 --> 00:52:27,180 of recognizing one dysmorphic feature 1118 00:52:27,180 --> 00:52:29,670 and then saying what other dysmorphic features 1119 00:52:29,670 --> 00:52:30,540 might go along with it, 1120 00:52:30,540 --> 00:52:31,770 and look for those, 1121 00:52:31,770 --> 00:52:33,930 and that helps you decide 1122 00:52:33,930 --> 00:52:37,290 what are the next steps to do. 1123 00:52:37,290 --> 00:52:40,500 It's very concise. Has great pictures. 1124 00:52:40,500 --> 00:52:41,643 Not a big book. 1125 00:52:42,630 --> 00:52:44,830 So if you're interested in this or 1126 00:52:46,800 --> 00:52:47,633 have a sense 1127 00:52:47,633 --> 00:52:49,560 that this is gonna come up frequently in your practice, 1128 00:52:49,560 --> 00:52:53,250 this is probably one of the go-to books. 1129 00:52:53,250 --> 00:52:55,080 The other book that you're maybe familiar with 1130 00:52:55,080 --> 00:52:58,017 is Smith's "Recognizable Patterns of Human Malformation", 1131 00:52:59,880 --> 00:53:01,470 which is in its seventh edition. 1132 00:53:01,470 --> 00:53:04,650 This is our geneticist bible 1133 00:53:04,650 --> 00:53:06,000 for 1134 00:53:06,000 --> 00:53:07,230 the more common 1135 00:53:07,230 --> 00:53:11,380 dysmorphic syndrome feature descriptions and pictures 1136 00:53:12,570 --> 00:53:14,370 somebody in your office has, 1137 00:53:14,370 --> 00:53:16,440 that's probably sufficient. 1138 00:53:16,440 --> 00:53:17,700 You don't necessarily need to buy it. 1139 00:53:17,700 --> 00:53:19,893 I think it's about 80 or 90 bucks now, 1140 00:53:21,090 --> 00:53:25,440 and it's a bigger, thicker, more detailed book. 1141 00:53:25,440 --> 00:53:28,200 So if you're an aficionado, this might be fun, 1142 00:53:28,200 --> 00:53:31,050 but if you can get access to it in your library 1143 00:53:31,050 --> 00:53:34,050 or somebody in your practice has it, then I wouldn't buy it. 1144 00:53:37,530 --> 00:53:39,250 All right, so that's the end.