Table 2.
Basic perinatal and clinical neurological data of subjects with biallelic variants in SLC38A3
| Family 1 | Family 2 | Family 3 | Family 4 | Family 5 | Family 6 | Family 7 | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| II-2 | II-3 | II-3 | II-4a | II-1 | II-3 | II-3 | II-4 | III-1 | II-5 | ||
| Basic clinical information and perinatal history | |||||||||||
| Gender | Male | Female | Female | Female | Female | Male | Female | Male | Male | Female | |
| Current age | 6 y | 5 y | 5 y | 6 y | 4 y | 3 y | 8 y | 3 y 2 mo | 1 y 3 mo | 13 mo | |
| Delivery | SVD, FT | SVD, PT (35) | SVD, FT | SVD, FT (38) | CS, FT | CS, FT | CS, FT (40) | CS, FT (39) | CS, FT | CS, FT (39) | |
| Perinatal complications | None | IUGR, HMD, jaundice | Low foetal movement | None | None | None | None | None | None | None | |
| OFC at birth | N/A | 30 cm | 32 cm | N/A | N/A | N/A | 31.5 cm | 32.5 cm | 33 cm | N/A | |
| (z-score) | (−3.26 SD) | (−1.9 SD) | (−2.2 SD) | (−1.5 SD) | (−1.3 SD) | ||||||
| Weight-birth | N/A | 3 kg | 2.8 kg | 2 kg | 4.3 kg | 3.5 kg | 3.2 kg | 3 kg | 3.2 kg | N/A | |
| (z-score) | (−0.8 SD) | (−1.2 SD) | (−2.7 SD) | (+1.8 SD) | (−0.1 SD) | (−0.4 SD) | (−0.9 SD) | (−0.6SD) | |||
| Neurological, developmental, and other clinical features | |||||||||||
| Age at last exam | 3 y | 5 y | 5 y | 5 y | 3 y 4 mo | 2 y | 7 y | 2 y 2 mo | 1 y 3 mo | 13 mo | |
| OFC at last exam | 46.5 cm | 44 cm | 47 cm | 42 cm | 51 cm | 43 cm | 46 cm | 43.8 cm | 44 cm | 43 cm | |
| (z-score) | (−2.5 SD) | (−4.5 SD) | (−2.4 SD) | (−6 SD) | (+1.4 SD) | (−4 SD) | (−4.4 SD) | (−3.4 SD) | (−2.4 SD) | (−1.82 SD) | |
| Axial hypotonia | + | + | + | + | + | + | + | + | + | + | 10/10 |
| Absent speech | + | + | + | + | + | + | + | + | + | + | 10/10 |
| GDD/ID | + | + | + | + | + | + | + | + | + | + | 10/10 |
| Visual impairment | + (CRD/CB) | + (CRD/CB) | + | − | + | + (CRD/CB) | + | + | + | + (CB) | 9/10 |
| Microcephaly | + | + (P)b | + (P) | + | − | + | + (P) | + (P) | + (P) | – | 8/10 |
| Seizures (onset) | + (4 mo) | + (10 mo) | + (15 mo) | + (1 w) | − | + (5 mo) | + (6 mo) | + (5 mo) | − | + (4 mo) | 8/10 |
| DRE (current ASMs) | + (PB, LEV, CLZ, VGB, keto) | + (PB, CLB, VGB, keto) | − (OXC, CLZ) | + (TPM, VPA) | − | + (TPM, VPA, CLZ) | − (VPA, LEV) | − (LEV) | − | + (PB, CLB, keto) | 5/10 |
| Seizure type and frequency | Tonic/4–11per day | ‘gelastic’/0–2 per day | Focal status epilepticus/4 life-time | GTC/daily | N/A | GTC | GTC/5 life-time (febrile; last 4 y ago) | Focal with generalization/once | N/A | Generalized myoclonic and tonic/∼10 per day | |
| Epileptic encephalopathy | + | + | + | + | − | − | − | − | − | + | 5/10 |
| Peripheral hypertonia | + | + | + | − | − | + | + | + | + | + | 8/10 |
| Constipation | + | + | + | + | − | − | + | + | + | + | 8/10 |
| Dysphagia | + (GT) | + (GT) | − | + | − | + | + | + | − | + (GT) | 7/10 |
| FTT | − | + | − | + | − | + | + | − | − | − | 4/10 |
| Hyperreflexia | + | + | − | − | − | + | − | − | − | + | 4/10 |
| Movement disorder | + | + | − | − | − | − | − | − | + | − | 3/10 |
| Other features | Behavioural problems | Behavioural problems | GERD; hepatomegaly; situs inversus totalis; ASD | Behavioural problems | GERD; behavioural problems | Behavioural problems | Recurrent stridor; Abnormal supra-glottis; s/p supra-glottoplasty | ||||
ASD = atrial septal defect; ASM = anti-seizure medication; CB = cortical blindness; CLB = clobazam; CLZ = clonazepam; CS = Caesarean section; CRD = cone-rod dystrophy; DRE = drug-resistant epilepsy; FT = full term; FTT = failure to thrive; GDD = global developmental delay; GERD = gastroesophageal reflex disease; GTC = generalized tonic clonic; GT = gastric tube; HMD = hyaline membrane disease; IUGR = intrauterine growth restriction; keto = ketogenic diet; LEV = levetiracetam; N/A = not available; OFC = occipitofrontal circumference; P = postnatal/progressive; PB = phenobarbital; PT = preterm; VGB = vigabatrin; SVD = spontaneous vaginal delivery; TPM = topiramate; VPA = valproic acid; w/mo/y = week/month/year; ZNS = zonisamide.
Previously published with limited clinical data.
Based on an OFC of 30 cm (−3.26 SD) at birth and 43.5 (−3SD) at 2.5 years of age