Table 1 The demographic, clinical, and genetic data of patients with biallelic ESAM variants
This study | Alshammari et al. [5] | Lecca et al. [2] | ||||
|---|---|---|---|---|---|---|
Patient 1(I.V.1) | Patient 2 (I.V.2) | Patient 3 (I.V.3) | Patient 4 (II.V.3) | Family 3 (III:5) | ||
Gender | F | M | M | F | M | 8 M/5 F/ 1 unknown |
Age at examination | 4 m | 1 y | 3½y | 4½y | 3 y | From 13 m to 13 y |
Ethnicity | Egyptian | NA | Turkish, Algerian, Spanish, Arab Bedouin | |||
Consanguinity | + | + | + | 12/14 | ||
Prenatal hydrocephalus | + | – | – | + | NA | 7/13 |
Weight in kg (z score) | 5.9 (mean) | 12.5 ( + 0.9) | 23 ( + 3) | 9.5 (-4) | NA | 7/9 <10th percentile |
Height in cm (z score) | 60 (mean) | 80 ( + 1.4) | 114 ( + 3) | 84 (-4.5) | NA | 8/8 <10th percentile |
OFC in cm (z score) | 41 (mean) | 47.5 ( + 0.7) | 51.5 (mean) | 45 (-5) | NA | 4/9 <10th percentile |
Neurological examination | ||||||
Hypertonia or spasticity | + | + | + | + | + | Spasticity (9/9) |
Exaggerated reflexes | + | + | + | + | + | + (9/9) |
Degree of developmental quotient | Severe | Severe | Severe | Severe | Severe | Severe (9/9) |
Seizures | + | + | – | + | + | + (9/9) |
Onset | 6 m | 1 y | – | 1 y | NA | NA |
Type | GTC | Focal, GTC | – | GTC | NA | Focal, GTC, myoclonic |
Status epilepticus | + | - | – | – | NA | NA |
Response to AEDs | fair | fair | – | fair | NA | NA |
Abnormal EEG | NA | Normal | Normal | Normal | NA | (2/9) showed hypsarrhythmia |
Imaging abnormalities | ||||||
Age at neuroimaging | 2 weeks, 3 m, 6 m | 4 m, 3 y 6 m | 3 weeks, 3 m, 1½y, 4 y | 4 y | Prenatal and first months of life | |
Porencephaly | + | + | + | + | + | + (3/9) |
Leukomalacia | + | + | + | + | + | + (3/9) |
abnormal myelination | + | + | + | + | + | + (5/9) |
Intracranial hemorrhage | + | + | + | + | Chronic intraventricular hemorrhage and hemorrhagic periventricular microcystic lesions | + (9/9) |
Ventriculomegaly | + | + Severe | + Mild | + | + Mild | + (9/9) |
Hydrocephalus | + | + Progressive | – | + | – | + (7/9) |
Intracranial calcification | + | + | + | + | – | + (8/9) |
Progressive ICH | + | + | – | + | – | – |
Fundus examination | NA | Normal | Pale optic disc, increased tortuosity of retinal blood vessels | Pale optic disc, increased tortuosity of retinal blood vessels | Severe strabismus | 4/9 (retinal ischemia, increased tortuosity of retinal blood vessels, retinal hemorrhage) |
Facial features | Macrocephaly, high forehead, deep seated eyes bulbous nasal tip, upturned nostrils | Macrodolicocephaly with frontal bossing, deep seated eyes, bulbous nasal tip, upturned nostrils, and long face | High forehead, bitemporal narrowing, arched eyebrow and bulbous nasal tip, upturned nostrils, long eyelashes, wide nasal bridge upslanted palpebral fissures, and bow shaped mouth | Asymmetry of head, high forehead, bulbous nasal tip, bow shaped mouth and high arched palate | NA | Bitemporal narrowing (6/9), highly arched eyebrow and bulbous nasal tip (5/9), long eyelashes (4/9), abnormal vermilion (4/9), high narrow palate (3/9), wide nasal bridge (3/9), upslanted palpebral fissures (3/9), and microretrognathia (2/9) |
Age of death | 15 m | 5 y | Alive | Alive | NA | 2/9 (at 5 y and 15 m) and 3 terminations of pregnancy and a still birth |
ESAM variant (NM_138961.3) | c.731-2A>G | c.561G>C (p.Trp187Cys) | c.344del (p.Gly115Valfs*14) | c.35T>A (p.Leu12*), c.115del (p.Arg39Glyfs*33), c.287del (p.Pro96Leufs*33), c.451+1G>A | ||
