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Table 1 Characteristics of 38 patients with intellectual disability and microcephaly on whom whole-exome sequencing was performed

From: Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly

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) 56 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) 13 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
  1. (a), (b), (c) indicating the three sib-pairs
  2. NA, not available
  3. OFC, occipital frontal head circumference (expressed in standard deviations below the mean (Z-score) according