Table 2 Clinical presentation and disease-causing variants identified in non-MD patients
Patient no./sex | Family history | Age of onset/age of last follow-up | Initial presentation | Muscular | CNS | Heart | Vision | Hearing | Neuro-imaging | MDC score (pre-biopsy) | Gene | Variant | Disease association |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
12/M | + (mother, sibling of patient 13) | 8 mo/24 yo | Non-syndromic | + | + | − | − | − | + | 8, definite | ATP1A3 | c.2452G>A, p.(Glu818Lys) | Alternating hemiplegia of childhood 2; CAPOS syndrome; Dystonia-12 |
13/F | + (mother, sibling of patient 12) | 7 mo/26 yo | Non-syndromic | + | + | − | − | − | − | 8, definite | ATP1A3 | c.2452G>A, p.(Glu818Lys) | Alternating hemiplegia of childhood 2; CAPOS syndrome; Dystonia-12 |
14/M | − | Birth/14 yo | Non-syndromic | + | + | − | − | − | − | 8, definite | ARX | c.989G>A, p.(Arg330His) hemizygous | Epileptic encephalopathy, early infantile, 1; hydranencephaly with abnormal genitalia; Lissencephaly, X-linked 2; Mental retardation, X-linked 29 and others; Partington syndrome; Proud syndrome |
15/F | + (paternal cousin) | Birth/14 yo | Non-syndromic | + | + | − | − | − | − | 7, probable | ATP1A3 | c.2755_2757del GTC, p.(Val919del) | Alternating hemiplegia of childhood 2; CAPOS syndrome; Dystonia-12 |
16/M | − | Infancy/4 yo | Non-syndromic | + | + | − | − | − | + | 8, definite | WAC | c.1171dupA, p.(Thr391Asnfs*15) | Desanto-Shinawi syndrome |
17/M | − | 3.5 yo/9 yo | Non-syndromic | − | + | − | − | − | + | 8, definite | ALDH5A1 | c.515G>A, p.(Arg172His) homozygous | Succinic semialdehyde dehydrogenase deficiency |
18/F | − | 9 yo/29 yo | Non-syndromic | − | + | − | − | − | + | 5, probable | FA2H | c.460C>T, p.(Arg154Cys) homozygous | Spastic paraplegia 35, autosomal recessive |
19/M | − | Infancy/26 yo | Non-syndromic | + | + | − | − | − | − | 5, probable | NEFL | c.293A>G, p.(Asn98Ser) | Charcot–Marie–Tooth disease, dominant intermediate G; type 1F; type 1E |
20/M | − | Neonatal/8 yoa | Non-syndromic | + | + | − | − | − | + | 8,definite | KCNT1 | c.1420C>T, p.(Arg474Cys) | Epilepsy, nocturnal frontal lobe, 5; Epileptic encephalopathy, early infantile, 14 |
21/F | − | Infancy/30 yo | Non-syndromic | + | + | − | − | − | + | 8, definite | NKX2-2 | c.32C>T, p.(Ser11Leu) homozygous | Diabetes—neonatal onset |
22/M | − | Infancy/10 yoa | Non-syndromic | + | + | − | − | − | + | 4, possible | TBCK | c.976dupT, p.(Tyr326Leufs*10) and c.478G>T, p.(Glu160*) | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 |
23/F | − | Infancy/13 yo | Non-syndromic | − | + | − | − | − | − | 4, possible | LDHD | c.469+1dup and c.752C>T, p.(Thr251Met) | D-lactic aciduria |