| p.Asp11Profs*14 (Present study) |
Patient VIII:2 |
F |
Birth
9 m |
26 (−9.7)
30.8 (−13.6) |
40 (−6.1)
55 (−5.3) |
1.5 (−3.7)
3.4 (−8.3) |
Severe intellectual disability, no speech (uses a few words), walked at age 2.7 (31 month) Sloping forehead, prominent metopic suture, upslanting palp. fissures, blepharophimosis, epicantus, large ears, prominent nose, thin upper lip, high arched palate, micrognathia, fifth finger clinodactyly. Skeletal findings: Delayed bone age, radius hypoplasia, epiphysiolysis in distal femur, slight cubbing and ill-defined epiphysis in all the tubular bones. Brain MRI: Microcephaly, simplified gyri |
| |
Patient VII:2* |
M |
|
− |
− |
− |
Severe intellectual disability. Sloping forehead, upslanting palp. fissures, blepharophimosis, epicantus, prominent nose micrognathia |
| p.Arg936fs*1 (ref. 8)
|
F1-P1 |
M |
Birth
12 y |
−
43 (−7.44) |
−
115 (−4.64) |
− |
Profound intellectual disability, no speech, can’t sit unaided, microcornea, cataract (R), contractures, epilepsy |
| |
F1-P2 |
F |
Birth
5 y |
−
35 (−13.98) |
−
78 (−6.9) |
− |
Profound intellectual disability, can’t sit unaided, no speech. microphthalmia, microcornea, corneal opacity with cataract (R). Skeletal findings: Lumbar scoliosis. Brain MRI: Microcephaly with simplified gyri, large interhemispheric arachnoid cyst, hypoplasia of pons and cerebellum, partial agenesis of corpus callosum (short), enlarged 4th ventricle |
| |
F1-P3 |
F |
Birth
10.5 y |
−
33 (−13.46) |
−
88 (−8.26) |
− |
Very severe intellectual disability, no speech (uses a few words), can’t sit unaided, few words. Polydactyly partial duplication right great toe, talipes equinovarus, 2/3 toe syndactyly (R+L), contractures, epilepsy |
| |
F1-P4 |
F |
Birth
1.5 y |
−
30 (−15.14) |
−
58 (−8.07) |
− |
Very severe intellectual disability, can’t sit unaided. Microphthalmia, microcornea, vitreous inclusions, contractures. Brain MRI: Microcephaly with markedly simplified gyri, hypoplasia of pons and cerebellum, partial agenesis of corpus callosum (short), venae galeni cyst, enlarged 4th ventricle |
| |
F1-P5 |
M |
Birth
6 m |
−
29 (−14.3) |
− |
− |
Very severe intellectual disability, speech with a few words, walked with support at age of 5.5y., died at age 5.5–congenital heart disease (septal defect) |
| p.Phe433fs*6 (ref. 8)
|
F2-P6 |
F |
Birth
20 y |
29 (−8.3)
43 |
46 (−5.5)
130 |
0.18 (−3.9)
— |
Severe intellectual disability, no speech. Early onset, severe vitreoretinal dystrophy, moderate, mixed deafness, café-au-lait and hypopigmented patches, camptodactyly. Skeletal findings: Severe scoliosis hip dysplasia. Brain MRI: Microcephaly with simplified gyri, short corpus callosum, periventricular heterotopia |
| |
F3-P7 |
M |
Birth
5 y |
21 (−4.5)
33.5 (−12.8) |
31
88 (−4.8) |
0.44 (−3.7)
—
|
Severe intellectual disability, can sit, but can’t walk, no speech. IUGR, oligohyraminos, pectus excavatum, brachdactyly, 5th finger clinodactyly and prominent nose, hyperactive, restricted knee extension, cryptorchidism, no ophthalmological assessment. Skeletal findings: Delayed bone age. Brain MRI: Microcephaly with simplified gyri, hypoplasia of pons and cerebellum, interhemispheric arachnoid cyst, agenesis of corpus callosum |
| p.Phe433Leufs*6 (ref. 9)
|
IV-4 |
F |
Birth
40 m |
26 (−5.9)
33 (−10.1) |
40 (−4.2)
68 (−7.2) |
−
4.5 (−6.9) |
Sloping forehead, prominent metopic suture, prominent eyes, strabismus, optic nerve hypoplasia micrognathia. Skeletal findings: Mild shorting of long bones, no frank dysplastic changes. Brain MRI: Microcephaly, arachnoid cyst |
| |
IV-5 |
M |
Birth
19 m |
−
31.5 (−11.8) |
−
58 (−6.4) |
−
3.7−(6.5) |
Sloping forehead, prominent metopic suture, prominent eyes, strabismus optic nerve hypoplasia, prominent nose, micrognathia. Skeletal findings: Mild shorting of long bones, no frank dysplastic changes, Brain MRI: Microcephaly arachnoid cyst |
| |
IV-2 |
F |
Birth
18 m |
27 (−5.2)
30.5 (−12.5) |
43 (−2.8)
56 (−7.5) |
1.9 (−2.9)
4 (−7) |
Sloping forehead, prominent metopic suture, prominent eyes, strabismus optic nerve hypoplasia, prominent nose, micrognathia |
