Table 1.
Case phenotype and genotype
| 2937-III-1 | 3308-III-1 | 3439-IV-3 | 3439-IV-4 | 3439-IV-5 | 3007-III-1 | GB31-II-6 | |
|---|---|---|---|---|---|---|---|
| Proband | |||||||
| Current age | 5 yrs F | Dec (3 yrs) | Dec (8 mos) | Dec (10 yrs) | 1.5 yrs | 10 mos | Dec (2.5 mos) |
| Gender | F | F | M | M | F | F | F |
| Ethnicity | Egyptian | Egyptian | Egyptian | Egyptian | Egyptian | Syrian | Caucasian |
| Consang | + | + | + | + | + | Distant | − |
| Variant | |||||||
| Zygosity | Homozygous | Homozygous | N/A | Homozygous | Homozygous | Homozygous | Compound heterozygous |
| Genomic (hg19) | chr6:g.31748303C>T | chr6:g.31747247G>A | N/A | chr6:g.31747247G>A | chr6:g.31747247G>A | chr6:g.31750317G>T | chr6:g.(31750138C>G;31753046G>A) |
| cDNA | c.2840G>A | c.3355C>T | N/A | c.3355C>T | c.3355C>T | c.1981C>A | c.(2074G>C; 1324C>T) |
| Protein | p.(Arg947His) | p.(Arg1119Cys) | N/A | p.(Arg1119Cys) | p.(Arg1119Cys) | p.(Pro661Thr) | p.(Ala692Pro;Arg442*) |
| Perinatal history | |||||||
| Gestation | Term | Term | Term | Term | Term | Term | Preterm (36 + 3 wks) |
| HC at birth (cm) | 33.5 (−0.9 SD) | 30 (−3.3 SD) | 31.5 (−2 SD) | 32.5 (−1.7 SD) | 32 (−1.25 SD) | 37 (+2.64 SD) | 30 (−2.06 SD) |
| Weight at birth (kg) | 2.53 (−1.7 SD) | 2.8 (−1 SD) | N/A | 3 (−1 SD) | 2.8 (−1.3 SD) | 3.55 (+0.67 SD) | 2.31 (−1.01 SD) |
| Length at birth (cm) | 46 (−1.6 SD) | 47 (−1 SD) | N/A | 48 (−0.6 SD) | 48 (−0.7 SD) | 53.3 (+2.25 SD) | 41 (−2.64 SD) |
| Complic | – | – | – | – | – | − | oligohyd; IUGR; seizures |
| Psychomotor development | |||||||
| Gross motor skills | Delayed | Severe delay | Severe delay | Severe delay | Severe delay | Delayed | Severe delay |
| Fine motor skills | Delayed | Severe delay | Severe delay | Ssevere delay | Severe delay | Delayed | N/A |
| Language | Delayed | Severe delay | Delayed | Severe delay | Delayed | Delayed | N/A |
| Social | Delayed | Severe delay | Severe delay | Severe delay | Severe delay | Delayed | N/A |
| Neurological examination | |||||||
| Age at last exam | 1 yr, 7 mos | 6 mos | 7 mos | 6 yrs | 1.5 yrs | 10 mos | 2 mos |
| HC (cm) | 40 (−4.6 SD) | 36 (−5.2 SD) | 38.2 (−4 SD) | 39 (−8.2 SD) | 37.5 (−6.8 SD) | 46.2 (+1.4 SD) | 30.5 (−6.5 SD) |
| Weight (kg) | 8 (−2.6 SD) | 5.5 (−2.1 SD) | 5.8 (−2.5 SD) | 7.7 (−5.8 SD) | 6.5 (−4.4 SD) | 9.5 (+0.85 SD) | 2.1 (−4.5 SD) |
| Length (cm) | 74 (−2.1 SD) | 63 (−0.8 SD) | 65 (−1.5 SD) | 97 (−3.6 SD) | 69 (−3.4 SD) | 69.5 (−0.97 SD) | 44 (−5.6 SD) |
| Tone | Axial hypotonia limb hypertonia | axial hypotonia limb hypertonia | axial hypotonia limb hypertonia | axial hypotonia, limb hypertonia | axial hypotonia limb hypertonia | axial hypotonia | axial and limb hypertonia |
| Reflexes | brisk | brisk | brisk | brisk | brisk | brisk | brisk |
| Extrapyram | + | + | + | + | + | − | − |
| Seizures | |||||||
| Onset | 3 mos | 3 wks | 2 wks | 1 wk | 40 d | 4 mos | 2 d |
| Type | Generalized, myoclonic, focal | Generalized, myoclonic, focal | Generalized, myoclonic, focal | Generalized, myoclonic, focal | Generalized, myoclonic, focal | Infantile spasms, tonic | Multifocal |
| Frequency | Rare | Weekly | Daily | Weekly | Daily | >10 per day | Daily |
| Control | Controlled | Refractory | Refractory | Controlled | Controlled | Controlled | Refractory |
| Treatments | Val | Val Lev | Val Lev Clon | Val Lev Clon | Lev Tia | Vig | Lev Phen Clon Lor |
| EEG | Right frontal epileptiform | Generalized discharges | Hypsarrhythmia | Generalized focus | Generalized discharges | Hypsarrhythmia | Diffuse multifocal epileptiform |
| Brain MRI | |||||||
| Age of MRI | 1 yr | 3 yrs | 4 mos | 3 mos / 4 yrs | 4 mos / 18 mos | 6 mos | 2 d |
| Findings | Cortical atrophy, mild central atrophy, hypoplastic CC | Cortical atrophy, abnormal gyration, hypoplastic CC | Cortical atrophy, hypoplastic CC | Progressive central and cortical atrophy, hypoplastic CC | Progressive cortical atrophy, hypoplastic CC | Normal | Severe atrophy and simplified gyral pattern; abn myelination hypoplastic CC |
| Systemic manifestations | |||||||
| Gastrointestinal | Feeding difficulties | Feeding difficulties, recurrent vomiting | Feeding difficulties, recurrent vomiting | Feeding difficulties, recurrent vomiting | Recurrent vomiting, AST slight elevation | Feeding difficulties, elevated AST/ALT, US: abn liver echo | Feeding difficulties, mild hepatomegaly |
| Other | VSD | PFO, Skeletal survey abn*, Dysmorphic** | |||||
+ present, − absent, d days, mos months, wks weeks, yr(s) years, dec deceased, Consang consanguinity, HC head circumference, SD standard deviations, Complic complications, oligohyd oligohydramnios, IUGR intrauterine growth restriction, Extrapyram extrapyramidal movements, Val Valproate, Lev Levetiracetam, Clon Clonazepam, Tia Tiagabine, Vig Vigabatrin, Phen Phenobarbital, Lor Lorazepam, CC corpus callosum, AST aspartate aminotransferase, ALT alanine aminotransferase, US ultrasound, abn abnormal, echo echogenicity, VSD ventriculoseptal defect, PFO patent foramen ovale
*11 ribs bilaterally, suspicion of congenital osteofibrous dysplasia of the right tibia
**Sloping forehead, prominent nasal bridge, apparent hypertelorism, upslanting and short palpebral fissure, large ears and a lumbar hemangioma