Table 1.
I-V-1 | II-V-1 | II-V-2 | III-IV-2 | IV-IV-1 | IV-IV-2 | V-IV-1 | V-IV-2 | VI-IV-1 | |
---|---|---|---|---|---|---|---|---|---|
cDNA mutations | c.1462delA, c.2617C>T | c.1959_1960insTT | c.1959_1960insTT | c.1686_1701del | c.199C>G | c.199C>G | c.3G>A | c.3G>A | c.1151G>A, c.2521dupA |
Proteins variants | p.Arg488Glufs∗6, p.Gln873∗ | p.Arg654Leufs∗6 | p.Arg654Leufs∗6 | p.Phe562Leufs∗8 | p.His67Asp | p.His67Asp | p.Met1? | p.Met1? | p.Gly384Glu, p.Ile841Asnfs∗4 |
Gender | female | female | female | male | female | male | male | female | male |
Country of origin | Egypt | Yemen | Yemen | Egypt | Lebanon | Lebanon | Turkey | Turkey | US |
Consanguinity | + | + | + | + | + | + | + | + | − |
Weight at birth (kg) | NA | NA | NA | 2 | 3.55 | 3.63 | 3.45 | 2.6 | 2.7 |
Length at birth (cm) | NA | NA | NA | 47 | 55 | 53 | NA | NA | NA |
HC at birth (SD) | NA | NA | NA | −1 | −1 | +1 | NA | NA | NA |
Psychomotor Development | |||||||||
Gross motor skillsa | delayed | delayed | delayed | delayed | delayed | delayed | delayed | delayed | delayed |
Fine motor skillsa | delayed | delayed | delayed | absent | delayed | delayed | delayed | delayed | delayed |
Languagea | delayed | delayed | delayed | absent | absent | absent | delayed | delayed | absent |
Sociala | delayed | delayed | delayed | delayed | delayed | delayed | delayed | delayed | delayed |
Neurological Examination | |||||||||
HC at last examination (cm) | 41 (−7.5 SDs) | NA | NA | 39.5 (−4 SDs) | 46 (−1.34 SDs) | 46.5 (−0.22 SD) | 49.5 (−1 SD) | 45 (−2 SDs) | 53 (+1.5 SDs) |
Age at diagnosis | NA | NA | NA | 6 months | 18 months | 6 months | 1 month | 5 months | prenatal: encephalocele on ultrasound |
Hypotonia | + | + | + | + | + | + | + | + | + |
Intellectual disability | + | + | + | + | + | + | + | + | + |
Autistic-like behavior | NA | + | + | − | NA | NA | − | − | NA |
Seizures | |||||||||
Onset | 4 months | 6 months | 8 months | 7 months | − | − | − | 5 months | 6 months |
Type | GTC | GTC | GTC | myoclonic | − | − | − | GTC | infantile spasms |
Frequency | weekly | weekly | under control | infrequent | − | − | − | weekly | daily |
Ophthalmologic Findings | |||||||||
Cataract | − | + (L) | NA | − | − | − | + (R) | − | − |
Micropthalmia | − | − | NA | − | − | − | + (L) | − | − |
Buphthalmos | − | − | NA | − | − | − | − | − | − |
Megalocornea | − | − | NA | − | − | − | − | − | − |
Optic atrophy | − | + | NA | − | − | − | − | − | − |
Retinal dysplasia | − | − | NA | − | − | − | − | − | − |
Other Systemic Findings | |||||||||
Cardiovascular | NA | − | NA | − | − | − | NA | − | − |
Respiratory | NA | − | NA | RD at birth | − | − | NA | − | − |
Musculoskeletal | NA | − | NA | club feet | club feet | − | NA | contractures of elbow | G-tube feeding due to hypotonia |
Genitourinary | NA | unilateral pubic adhesion | − | − | − | − | NA | − | − |
Other | − | − | occipital lipoma | squint | − | − | facial asymmetry | hypertelorismus, strabismus, sacral hemangioma | squint |
MRI | |||||||||
Agyria | + | + | + | + | − | − | − | − | − (PMG) |
Cobblestone lissencephaly | + | + | + | + | − | − | + | + | + |
Ventriculomegaly | + | + | + | − | + | + | + | − | + |
Encephalocele | + (occipital) | − | − | − | − | − | − | − | + (occipital) |
Corpus callosum | hypoplasia | − | − | hypoplasia | hypoplasia | hypoplasia | − | − | partial hypoplasia |
Brainstem | dysplasia, hypoplasia | hypoplasia | hypoplasia | hypoplasia | hypoplasia | hypoplasia | − | − | − |
Cerebellum | dysplasia | hypoplasia | hypoplasia | hypoplasia | dysplasia | dysplasia | − | − | − |
Retrocerebellar cysts | − | − | − | + | − | − | − | − | − |
Investigations | |||||||||
CPK level (units/liter) | normal | NA | NA | normal | normal | normal | normal | elevated (650) | elevated (1,025) |
Other metabolic findings | NA | normal | increased GGT and ALP | normal | normal | normal | normal | normal | normal |
VEP/ERG | NA | NA | NA | normal | NA | NA | NA | NA | normal |
EMG | normal | NA | NA | normal | NA | NA | NA | NA | NA |
Muscle biopsy | NA | NA | NA | NA | NA | NA | NA | NA | mild myopathic change, increased interstitial collagen, fiber-size variation |
Abbreviations: ALP, alkaline phosphatase; CPK, creatine phosphokinase; EMG, electromyography; GGT, gamma glutamate transferase; GTC, generalized tonic clonic; HC, head circumference; L, left; NA, not available; PMG, polymicrogyria; R, right; RD, respiratory distress; and VEP/ERG, visual evoked potential and electroretinogram.
Normal, delayed, or absent.