Table 1 Characteristics of 38 patients with intellectual disability and microcephaly on whom whole-exome sequencing was performed
Patient | Age | Sex | OFC (Z-score) | Brain imaging (MRI) | Additional clinical features |
|---|---|---|---|---|---|
1 | 8 years | f | −3.0 | Thin corpus callosum, mild enlarged ventricles, hypoplasia of vermis and cerebellum | Bilateral congenital cataracts, microphthalmia, pale optic discs, hypogenitalism, axial hypotonia, hip dislocation, joint contractures, severe intellectual disability |
2 | 5 years | f | −5.3 | Mild enlarged ventricles | Intra-uterine growth retardation, neonatal hypoglycaemia, sensineural deafness, moderate intellectual disability |
3 | 3 years | f | −6.3 | Simplified gyral pattern, thin corpus callosum, wide peripheral liquor spaces | Feeding problems, recurrent respiratory infections, seizures, severe developmental delay |
4 | 2 years | m | −4.6 | Normal | Chorioretinopathy, mild developmental delay, hip dysplasia (mother with microcephaly and learning problems) |
5 | 8 years | m | −3.3 | Normal | Hypotelorism, cryptorchid testis, short stature, mild myopia, hyperactivity, intellectual disability |
6 | 31 year | f | −5.0 | NA | Mild intellectual disability, seizures, behavioural problems (brother with intellectual disability and microcephaly) |
7 | 4 years | m | −3.6 | Thin corpus callosum, delayed myelinisation, hypoplasia of frontal lobes | Strabismus, myoclonic jerks, spastic paraplegia, severe developmental delay |
8(a) | 5 years | f | −4.4 | Diffuse pachygyria | Short stature, moderate intellectual disability, bilateral metatarsus primus varus |
9(a) | 10 year | f | −5.2 | Mild frontal lissencephaly, posterior frontal pachygyria and parieto-occipital subcortical band heterotopia | Short stature, Tetralogy of Fallot, embryotoxon posterior, moderate intellectual disability (sister of patient 8) |
10(b) | 56Â years | f | NA | Normal CT-scan | Severe microcephaly, chorioretinopathy, seizures, autism spectrum disorder, severe intellectual disability |
11(b) | 57 years | f | −7.1 | NA | Chorioretinopathy, seizures, autism spectrum disorder, severe intellectual disability (sister of patient 10) |
12 | 3 years | m | −4.6 | Temporal and parieto-occipital atrophy | Cryptorchid testes, spasticity, feeding problems, nephrocalcinosis, seizures, severe developmental delay |
13 | 10 year | m | −5.0 | Simplified gyral pattern, mild cerebellar vermis hypoplasia | Hyperactivity, behavioural problems, speech delay, mild-moderate intellectual disability |
14 | 1 year | m | −3.2 | Megacisterna magna, prominent sulci of cerebellum | Brachycephaly, carp shaped mouth, uplifted ear lobes, mild hypotonia, developmental delay |
15 | 0.5 years | f | −7.0 | Simplified gyral pattern, sub-cortical areas with high signal intensity, prominent ventricles, small cerebellum | Infantile spasms, hyperkinesia, hypertonia, feeding problems, severe developmental delay |
16 | 3 years | m | −3.3 | Leucodystrophy, cerebral and cerebellar atrophy | Short stature, truncal hypotonia, spasticity, contractures, scoliosis, deafness, pigmentary retinopathy, mildly enlarged liver and elevated aminotransferase, feeding problems, cryptorchid testis, severe developmental delay, progressive disease course (consanguineous parents) |
17 | 2 years | f | −3.0 | NA | Short stature, embryotoxon posterior, feeding problems, developmental delay |
18 | 23 years | m | −3.0 | Hypoplasia of cerebral and cerebellum hemispheres, large cisterna magna, abnormal myelinisation | Seizures, hypotonia, thoracic kyphosis, camptodactyly, horseshoe kidney, small penis, auto mutilation, severe intellectual disability |
19 | 22 years | f | −4.0 | Atrophy, mild enlarged ventricles on CT-scan | Umbilical hernia, hip dysplasia, scoliosis, spasticity, feeding problems, severe intellectual disability, seizures, no speech, prominent upper incisors |
20 | 4 years | m | −3.9 | Normal | Metopic ridge, pancreas annulare, unilateral cleft lip and palate, short stature, severe developmental delay |
21 | 11 year | f | −4.8 | Hypoplasia frontal lobes, delay of myelinisation | Chorioretinopathy, mild cortical cataracts |
22 | 5 years | f | −8.0 | Delayed myelinisation, thin corpus callosum | Severe intellectual disability, hyperactivity disorder |
23 | 2 years | m | −4.9 | Wide peripheral liquor spaces | Low birth weight, brachycephaly, hypertonia, severe developmental delay (consanguineous parents) |
24 | 19 years | f | −3.0 | Focal temporal cortical dysplasia | Postnatal growth retardation, obesity, seizures, primary amenorrhea, hepatocellular carcinoma, mild-moderate intellectual disability with regression |
25 | 2 years | m | −4.5 | Normal | Short stature, adducted thumbs, hyperinsulinism, hypothyroidism, feeding problems, developmental delay |
26 | 5 years | f | −3.9 | Multiple intra cerebral calcifications on CT-scan | Feeding problems, short stature, seizures, spasticity, severe developmental delay |
27(c) | 5 years | m | −4.5 | Diffuse polymicrogyria | Seizures, ventricle septum defect, feeding problems, spasticity, severe developmental delay (consanguineous parents) |
28(c) | 13Â years | f | NA | Diffuse polymicrogyria | Severe microcephaly, seizures, spasticity, severe intellectual disability (sister of patient 27) |
29 | 1 year | f | −3.0 | Normal | Feeding problems, recurrent ear infections, vesicoureteral reflux, developmental delay (consanguineous parents) |
30 | 1 year | f | −5.2 | Simplified gyral pattern, hypoplasia of frontal lobes and corpus callosum | Low birth weight, mild developmental delay |
31 | 3 years | m | −3.4 | Normal | Microtia, iris and choroid coloboma, blepharophimosis, hypertelorism, micropenis, short stature, ventricle septum defect, inguinal hernia, feeding problems, developmental delay (consanguineous parents) |
32 | 14 years | f | −6.8 | Simplified gyral pattern | Seizures, behavioural problems, short stature, obesity, severe intellectual disability |
33 | 2 years | f | −3.1 | Mild delay of myelinisation, wide liquor spaces | Multicystic renal dysplasia, liver cysts and liver fibrosis, insulin-dependent diabetes, sick thyroid syndrome, hypertension, mixed hearing loss, developmental delay, mild complex III deficiency |
34 | 0 year | f | −3.9 | Abnormal gyration and myelinisation, small cerebellum | Intra-uterine growth retardation, maternal oligohydramnios, progressive renal failure (diffuse mesangial glomerulo sclerosis), beaked nose, large floppy ears, long fingers |
35 | 4 years | m | −4.4 | Possible polymicrogyria | Myopia, severe developmental delay |
36 | 16 years | f | −3.7 | Abnormal gyration parieto-temporal, hypoplasia posterior part of corpus callosum | Short stature, behavioural problems, mild mental retardation |
37 | 2 years | m | −3.5 | Small brain, no other abnormalities | Short stature, atrial septum defect, hypotonia, hypospadia, blepharophymosis, ear tag, developmental delay |
38 | 0.5 years | m | −5.2 | Wide peripheral liquor spaces, abnormal gyration fronto-parietal, small vermis, small pons | Peripheral hypertonia, axial hypotonia, seizures, feeding problems, developmental delay |