Table 1. Clinical Phenotypes.
Patients display acquired microcephaly, hypotonic cerebral palsy, inability to ambulate or speak, and intractable seizures. HC, head circumference; SD, standard deviation below the mean; B/L, bi-lateral; VEP, visual evoked potential; ERG, electroretinogram; EEG, electroencephalogram.
| Family-1101-1-IV-2 | Family 1101-2-IV-2 | Family-1101-3-IV-1 | Family-1101-3-IV-4 | Family-1263-1 | Family-1263-2 | Family-4727-IV-1 | |
|---|---|---|---|---|---|---|---|
| Gender | F | F | F | M | M | F | F |
| Origin | Saudi | Saudi | Saudi | Saudi | Turkish | Turkish | Saudi |
| Weight at birth (kg) | 2.9 | N/A | N/A | N/A | 2.7 | 2.5 | 3.5 |
| Length at birth (cm) | 46 | N/A | N/A | N/A | 49 | 48 | N/A |
| HC at birth (cm) | 35.5 | N/A | N/A | N/A | N/A | N/A | N/A |
| HC at birth (SD) | 0 | N/A | N/A | N/A | N/A | N/A | N/A |
| HC at last examination (cm) | 50 | 53.5 | 53 | 51 | 44 | 47 | 46.5 |
| HC at last examination (SD) | −4 | −1/0 | −1 | −2/−1 | −5 | −5 | −5 |
| Diagnosis age | 2 yrs | 1.5 yrs | 1 yr | Birth | 30 mos | 9 yrs | 28 mos |
| Intellectual Disability | Severe | Severe | Severe | Severe | Severe | Severe | N/A |
| Development | |||||||
| Gross motor (normal/delayed/absent) | Delayed | Delayed | Delayed | Delayed | Delayed | Absent | Delayed |
| Fine motor (normal/delayed/absent) | Delayed | Delayed | Delayed | Delayed | Delayed | Absent | Delayed |
| Language (normal/delayed/absent) | Single words | Single words | Single words | Absent | Absent | Absent | Absent |
| Social (normal/delayed/absent) | Delayed | Delayed | Delayed | Delayed | Delayed | Absent | Delayed |
| Seizures | |||||||
| Onset | 2–3 yrs | 1.5 yrs | 6 mos | 3 yrs | 8 mos | 6 mos | 6 mos |
| Type | Variable-atonic | Atonic/myoclonic | Variable-atonic | Variable-atonic | Atonic/myoclonic | Atonic/myoclonic | Infantile spasm (hypsarrhythmia) |
| Frequency | 1–2/week | 1–2/week | 1–2/week | 1–2/week | monthly | monthly | N/A |
| Neurological Findings | |||||||
| Hypertonia | − | − | − | − | − | − | + |
| Hypotonia | + | + | − | + | + | + | + (truncal) |
| Deep tendon reflexes | Increased | Increased | − | Increased | Increased | Increased | Increased |
| Spastic tetraplegia | + | − | − | + | − | + | + |
| Ataxia | Nonambulatory | + | + | Nonambulatory | − | Nonambulatory | Nonambulatory |
| Investigations | |||||||
| Metabolic | Normal | Normal | Normal | Normal | N/A | N/A | Negative |
| VEP/ERG | Normal | Normal | N/A | Abnormal | N/A | N/A | N/A |
| EEG | Abnormal | Abnormal | Abnormal | Abnormal | Abnormal | Abnormal | Abnormal |
| MRI | |||||||
| Lissencephaly spectrum | Pachygyria | Pachygyria | Pachygyria | Pachygyria | Pachygyria | Pachygyria | Pachygyria |
| Cerebral mantle thickening (normal 5 mm) | 9–30mm | 12–35mm | 10–30mm | 10–32mm | 12–22mm | 9–24mm | 9–35mm |
| Subcortical band heterotopia | − | − | − | − | − | − | − |
| Corpus callosum | N/A | N/A | thin | thin | thin | thin | thin |
| Cerebellar hypoplasia | Y | Y | Y | Y | Y | Y | Y |
| Brainstem hypoplasia | N | N | N | N | N | N | Y |
| Hydrocephalus | N | N | N | N | N | N/A | N/A |
| White matter paucity | Y | Y | Y | Y | Y | Y | N/A |
| White matter signal | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
| Miscellaneous | |||||||
| Polyhydramnios | − | − | − | − | − | − | − |
| Lung hypoplasia | − | − | − | − | − | − | − |
| Short stature | − | − | − | − | − | − | − |
| Macrocephaly | − | − | − | − | − | − | − |
| Optic atrophy | − | − | − | − | − | − | − |
| Autistic features | + | + | + | + | + | + | + |
| Dysmorphism | − | − | − | − | B/L pes equinovarus | − | − |