Clinical features of eight affected individuals from families A and B
| Patient | Family A | Family B | ||||||
|---|---|---|---|---|---|---|---|---|
| 1 (male) | 2 (male) | 3 (male) | 4 (male) | 5 (female) | 6 (female) | 7 (male) | 8 (male) | |
| Gestation at birth (weeks) | 38 | 40 | 40 | 40 | 41 | 39 | 40 | 40 |
| Birth weight (kg) | 2.26 (2nd centile) | 3.3 (25th centile) | 3.85 (50th–75th centile) | 3.74 (50th–75th centile) | 4.05 (91st centile) | 3.37 (mean) | 3.4 (−0.9 SD) | 3.2 (−1.5 SD) |
| Birth OFC (cm) | 36.0 (91st–98th centile) | 36.4 (75th–91st centile) | 38.2 (98th–99th centile) | 38.4 (98th–99th centile) | 35.4 (75th–91st centile) | 33 (−1.2 SD) | 34 (−1.8 SD) | 34.5 (−1.1 SD) |
| Hypogenitalism | Yes | No | Yes | Yes | No | No | No | No |
| Lower limbs | Bilateral spasticity | Bilateral spasticity | Bilateral spasticity | Bilateral spasticity | Bilateral spasticity | – | – | Bilateral spasticity |
| Upper limbs | Normal examination | Dystonic posturing | Normal examination | Normal examination | Increased tone and hyperreflexia | Normal | Dystonic posturing | Normal |
| Epilepsy | Myoclonic and tonic–clonic epilepsy from 7 months | Myoclonic and tonic–clonic seizures from 5 years | None | Tonic–clonic epilepsy from 10 years | Myoclonic epilepsy from infancy | None | Myoclonic seizures, focal epilepsy | None |
| Recent growth parameters | ||||||||
| Age | 18 years | 15 years | 22 years | 19 years | 3 years | 10 years 11 months | 7 years 8 months | 7 years 8 months |
| BMI (kg/m2) | 33.3 | 37 | 55.7 | 50.4 | 20.6 | 24.8 | 21.17 | 19.32 |
| OFC (cm) | 59 (75th–91st centile) | 59 (91st–98th centile) | 64 (>99th centile) | 63 (>99th centile) | 47.2 (<0.4th centile) | 54 (+0.5 SD) | 53 (+0.2 SD) | 53 (+0.2 SD) |
| Mobility | Never walked | Never walked | Age 16: mobile for short distances with callipers | Age 15: 10–15 steps with a rollator | Never walked | Unstable, waddling gait | Unstable, waddling gait | Unstable, waddling gait |
| Ophthalmic findings | Divergent strabismus | Divergent strabismus | Right divergent strabismus, bilateral myopia, right macular hypoplasia, retinal dystrophy | Divergent strabismus, myopia, bilateral retinal dystrophy | Severe myopia, left divergent squint, sluggish pupil responses, retinal dystrophy | Convergent strabismus, bilateral myopia, retinal dystrophy | ||
| Hearing | Bilateral sensorineural loss (40 dB) | No abnormality | Bilateral sensorineural loss (30 dB) | No abnormality | Bilateral sensorineural loss (40 dB) | No abnormality | No abnormality | No abnormality |
| Neurological investigations | CT scan: cerebral underdevelopment and marked atrophy of frontal and temporal lobes. EEG: consistent with myoclonic epilepsy | No cranial imaging performed | CT scan: generalised cerebral atrophy | EEG: normal CT scan: ventricular dilatation | EEG: focal and generalised spike-like discharges. Nerve conduction studies normal. MRI brain: prominent generalised cerebral and brain stem atrophy, disproportion between grey and white matters. ERG: Consistent with cone-rod dystrophy | MRI: hypoplastic corpus callosum EEG: normal | MRI: hypoplastic corpus callosum EEG: consistent with myoclonic epilepsy | MRI: enlarged ventricles EEG: normal |
| Skeletal | Left talipes equinovarus Kyphosis | Erb's palsy Right subtalar fusion age 9 years | Calcaneovalgus deformity of feet | Kyphoscoliosis Bilateral hip dislocation | Pes planus | Mild talipes equinovarus | ||
BMI, body mass index; ERG, electroretinography; OFC, occipitofrontal head circumference.