Table 1 Clinical, neuroimaging and genetic features of 21 patients with "congenital ocular motor apraxia type Cogan" (COMA)
Patient # (origin) | Sex | Current age (years) | Development | Neurological findings | MRI features | Mutated gene, pathogenic variants | Diagnostic assignment | References | |
|---|---|---|---|---|---|---|---|---|---|
Ocular apraxia [age at onset (months)/course/age at disappearance] | Early onset ataxia | ||||||||
1 (A) | f | 10 | SD, LD | 3/↓/− | Yes | MTS, vermian hypo-/dysplasia | MKS1 comp. het., c.1115_1117delCCT (p.Ser372del), c.1476T > G (p.Cys492Trp) | JBTS28 | |
2 (D) | m | 13 | UWD, SD, LD | 8/↓/− | Yes | MTS, superior vermian hypoplasia, slightly enlarged external csf spaces | CC2D2A comp. het., c.3289delG (p.Val1097Phefs*2) (possible splice change), c.4583G > A (p.Arg1528His) | JBTS9 | |
3 (D) | f | 18 | UWD, CDN | 3/↓/− | No | Normal | ES provided no conclusive result | “COMA “ | |
4 (D) | m | 24 | UWD, SD, LD | 3/↓/− | Yes | MTS, superior vermian dysplasia | TMEM67 comp. het., c.622A > T (p.Arg208*), c.1634G > A (p.Gly545Glu) | JBTS6 | |
5 (TR) | f | 12 | UWD, SD, ID | 4/↓/− | Yes | MTS, superior vermian hypo-/dysplasia | ES provided no conclusive result | JBTS | |
6 (D) | f | 10 | UWD, CDN | 6/↓/− | Yes | vermian dysplasia, otherwise normal | KIAA0586 comp. het., c.428delG (p.Arg143Lysfs*4), c.3888delC (p.Ile1297Serfs*19) | JBTS23 | |
7 (TR) | m | 24 | UWD, SD, CDN | 6/ ↔ /− | Yes | cerebellar cysts, cerebellar hypoplasia, square 4th ventricle | LAMA1 hom., c.756delT (p.Ile252Metfs*10) | PTBHS | |
8* (D) | m | 30 | UWD, SD, ID | 6/↓/4 years | Yes | MTS, vermian hypo-/dysplasia | KIAA0586 comp. het., c.428delG (p.Arg143Lysfs*4), c.1413-1G > C (splice site variant) | JBTS23 | [5] |
9* (D) | f | 27 | SD, LD | 11/↓/5 years | Yes | MTS, otherwise normal | KIAA0586 comp. het., c.428delG (p.Arg143Lysfs*4), c.1413-1G > C (splice site variant) | JBTS23 | [5] |
10 (T) | m | 15 | UWD, SD, LD | 6/↓/− | Yes | SCP mildly horizontalized, elongated, thickened, inferior vermian dysplasia, upper vermis split | SUFU het., c.83C > A (p.Ser28*) | forme fruste of JBTS | [6] |
11 (D) | m | 22 | UWD, SD, CDN | 2/↓/− | No | Normal | NPHP1 hom. deletion of whole gene | JBTS4 | |
12 (D) | f | 13 | UWD, SD | 10/↓/− | Yes | Normal | ES provided no conclusive result | “COMA” | |
13 (D/UK) | m | 9 | UWD, CDN | 8/↓/− | Yes | MTS, otherwise normal (mild superior vermian hypo-/dysplasia??) | KIAA0586 comp. het., c.428delG (p.Arg143Lysfs*4), deletion of exons 8, 9 and 10 | JBTS23 | |
14 (CH) | m | 13 | UWD, SD, CDN | 6/↓/− | Yes | SCP mildly horizontalized, elongated, thickened, mild vermis folia dysplasia, upper vermis split | SUFU het., c.1099G > T (p.Glu367*) | forme fruste of JBTS | [6] |
15 (D) | m | 12 | UWD, SD, ID | 8/↓/− | Yes | MTS, superior vermian dysplasia | NPHP1 hom. deletion of whole gene | JBTS4 | |
16* (D) | m | 28 | UWD, SD, CDN | 6/↓/− | Yes | MTS, vermian hypo-/dysplasia | KIAA0586 comp. het., c.428delG (p.Arg143Lysfs*4), deletion of exons 8, 9 and 10 | JBTS23 | |
17* (D) | m | 24 | UWD, SD, CDN | 3/↓/− | Yes | MTS, superior vermian hypo-/dysplasia | KIAA0586 comp. het., c.428delG (p.Arg143Lysfs*4), deletion of exons 8, 9 and 10 | JBTS23 | |
18 (D) | f | 29 | UWD, LD | 4/↓/− | Yes | Normal | ATM comp. het., c.1066-6T > G (p.?), c.2250G > A (p.Ile709_Lys750del) | variant A-T | [7] |
19 (D) | f | 12 | normal | 6/↓/− | No | SCP mildly horizontalized, elongated, thickened, superior vermian dysplasia, upper vermis split | SUFU het, c.479delA (p.His160Leufs*20) de novo | forme fruste of JBTS | [6] |
20 (R/K) | m | 17 | UWD, SD, ID | 5/↓/− | Yes | Enlarged ventricles, dysmorphic basal ganglia, hypoplastic corpus callosum, abnormal proportions of brainstem, suspicious of tubulinopathy | TUBA1A het., c.82C > T (p.His28Tyr), de novo | TUBA1A-associated brain malformation | |
21 (D) | m | 12 | UWD, SD, LD | 8/↓/− | Yes | MTS, callosal agenesis, vermian hypo-/dysplasia, hippocampal malrotation, dysplastic tectal plate | RPGRIP1L two het. variants on the same (maternal) allele, likely not causative: c.171G > T (p.Leu57Phe), c.628A > G (p.Asn210Asp) | JBTS | |