Table 1.
Family 1 |
Family 2 |
Family 3 |
Family 4 |
Family 5 |
Family 6 |
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II-2 | II-2 | II-2 | II-4 | II-5 | II-3 | II-4 | II-1 | II-2 | II-1 | II-2 | II-3 | |
Gender | female | male | male | male | male | male | male | female | female | male | male | female |
Ethnic origin | Hispanic | Hispanic/Italy | Egypt | Egypt | Egypt | Syria | Syria | Palestine | Palestine | Turkey | Turkey | Turkey |
Age at last examination | 18 years, 2 months | 17 years, 2 months | 13 years (died same year) | 8 years, 1 month | 3 years | 9 years, 5 months | 3 years, 11 months | 5 years, 4 months | 3 years, 2 months | 20 years, 7 months | 16 years, 6 months | 14 years, 8 months |
Intellectual disability | severe | severe | severe | severe | severe | severe | severe | severe | severe | moderate | mild | moderate |
Speech delay | no words | no words | no words | no words | no words | no words | no words | no words | no words | no delay | no delay | no delay |
Seizure (onset) | + (12 months) | + (15 months) | + (NA) | + (NA) | + (NA) | + (17 months) | + (3 years) | + (7 months) | + (2 years) | + (18 months) | + (7 years) | + (8 years) |
IUGR | + | + (poor fetal activity) | + | + (poor fetal activity) | + | + | + | − | − | − | − | − |
Weight, kg (z-score) | 28 (−8.9) | 47.6 (−2.2) | 15 (−2.2) (at 10 years) | 12 (−4.5) (at 5 years) | 9 (−3.5) | 15.5 (−1.6) (at 5 years 2 months) | 15 (−1) | 15.6 (−1.4) | 10 (−3.4) | 67 (−0.33) | 66 (0.27) | 54 (0.27) |
Height, cm (z-score) | 129.5 (−5.2) | 137 (−4.9) | 103 (−5) (at 10 years) | 90 (−3.8) (at 5 years) | 80 (−3.7) | 107 (−0.6) (at 5 years 2 months) | 93 (−2.5) | 100 (−2.1) | 87 (−2.0) | 176 (−0.1) | 171 (−0.5) | 159 (−0.4) |
OFC, cm (z-score) | 47.9 (−4.7) | 52 (−2.8) | 44.5 (−6.5) (at 10 years) | 44 (−5.3) (at 5 years) | 43 (−5.3) | 46.5 (−3.5) (at 5 years 2 months) | 45 (−4.3) | 45 (−4.5) | 44 (−4.3) | 55.7 (−0.35) | 54.5 (−0.59) | 54.3 (0.38) |
Hypotonia | + | + | + | + | + | + | + | + | + | − | − | − |
Gross motor delay | congenital quadriplegic, mostly in wheelchair | walked at 3 years 9 months but now non-ambulatory | could sit, non-ambulatory | sits, non-ambulatory | does not sit, non-ambulatory | walked 4 years 6 months | sits, non-ambulatory | crawled at 3 years; stands and walks only with support | does not crawl or pull to stand, non-ambulatory | no delay | no delay | no delay |
Feeding difficulties | + | + | + | + | + | + | + | + | + | − | − | − |
Others | FTT, chronic constipation, G-tube feeds | FTT, chronic constipation and diarrhea, G-tube feeds | FTT | FTT | FTT | FTT | FTT, G-tube feeds | |||||
Additional neurologic features | congenital quadriplegia, ataxia, spasticity | cerebral palsy, ataxia, spastic quadriplegia | autism spectrum disorder | autism spectrum disorder | autism spectrum disorder | − | − | − | − | − | − | − |
Brain imaging | normal | prominent perivascular spaces, hypoplastic corpus callosum, generalized white matter volume loss, gliosis in bilateral parietal lobes | mild fronto-parietal cortical changes | mild fronto-parietal cortical changes, short corpus callosum | mild fronto-parietal cortical changes | normal | cortical and white matter atrophy | mild dilatation of lateral ventricles mainly occipital horns, deep interhemispheric fissure/hypoplastic corpus callosum | normal | normal | normal | normal |
Physical Features | ||||||||||||
CHD | NA | normal echo | PS, ASD | normal echo | PS, ASD, VSD | NA | VSD | NA | TOF, ASD | NA | NA | NA |
Other congenital malformations | sacral dimple | spina bifida occulta, cryptorchidism | − | cryptorchidism | − | cryptorchidism | sacral dimple cryptorchidism | − | − | − | − | − |
Head/Neck | displaced posterior hair whorl | brachycephaly, sparse hair | short neck, sloping shoulders | short neck, sloping shoulders | short neck, sloping shoulders | − | − | flat occiput, sparse hair | flat occiput | wide forehead, narrow long asymmetric face | wide forehead, narrow long face | narrow long face |
Eyes | arched eyebrows, long eyelashes, long palpebral fissures | arched eyebrows, long down-slanting palpebral fissures, ptosis | long palpebral fissures | long palpebral fissures | long palpebral fissures | long palpebral fissures | − | arched eyebrows, deep-set eyes, long eyelashes | deep-set eyes, long eyelashes | down-slanting palpebral fissures | − | − |
Nose | long nose, hypoplastic alae, high nasal bridge, long philtrum | prominent nasal bridge, short columella, small alae, smooth long philtrum | broad root and prominent nasal bridge, smooth long philtrum | broad root and prominent nasal bridge, smooth long philtrum | broad root and prominent nasal bridge, smooth long philtrum | − | − | slightly long philtrum | slightly long philtrum | tubular nose | − | − |
Mouth/Chin | high arched palate, cupid bow, dental crowding | thin upper lip, downturned mouth corners, high arched palate, mild retrognathia | very thin upper lip, retrognathia | very thin upper lip, retrognathia | very thin upper lip, retrognathia | − | − | thin upper lip | thin upper lip | high arched palate, dental malocclusion, narrow chin | high arched palate, narrow chin | high arched palate |
Ears | − | posteriorly rotated ears, bilateral pits | large protruding low-set ears | large protruding low-set ears | large protruding low-set ears | large ears | large ears | large ears | large ears | prominent, dysplastic ears | − | − |
Scoliosis | + | + | + | − | − | − | + | + | − | − | − | − |
Extremities | broad thumbs, tapered fingers, long first toes, joint contractures, brachydactyly of other toes, hallux valgus | broad thumbs, bulbous finger tips, forearm asymmetry, feet turned outward, joint contractures overriding toes, planovalgus | broad thumbs, clubbed fingers, clubfoot | broad thumbs, hyperextensibility of interphalangeal joints, overriding toes | broad thumbs, hyperextensibility of interphalangeal joints, overriding toes | broad thumbs and first toes, fetal pads | − | bilateral toe syndactyly | bilateral toe syndactyly | arachnodactyly | hyperextensiblity of elbows | arachnodactyly, hyperextensibility of elbows |
Abbreviations are as follows: IUGR, intrauterine growth restriction; OFC, occipitofrontal circumference; NA, not available; CHD, congenital heart disease; PS, pulmonic stenosis; VSD, ventricular septal defect; ASD, atrioseptal defect; TOF, tetralogy of Fallot; FTT, failure to thrive. For weight and height, data were obtained from last examination, unless otherwise noted. Z-scores were calculated using the CDC charts for children ages 2–20. For head circumference, z-score was calculated based on published data.38