Table 1.
Family | 1 | 2 | 3 | 4 | 5 | 6 | 7 | Summary of our 9 patients | Summary of previously reported 67 patients1–19 | Total summary of all 76 patients | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Subject | 1.1 | 1.2 | 2.1 | 2.2 | 3.1 | 4.1 | 5.1 | 6.1 | 7.1 | |||
Sex | F | F | M | F | M | M | F | F | F | 3 male | 13 male | 16 male |
6 female | 12 female | 18 female | ||||||||||
42 NA | 42 NA | |||||||||||
Status | Alive | Alive | Deada | Alive | Alive | Alive | Deadb | Alive | Alive | 7 Alive | 14 Alive | 21 Alive |
7y | 2y | 14y | 15y | 5y | 7y | 1y | 4y | 2y | 2 Dead | 20 Dead | 22 Dead | |
33 NA | 33NA | |||||||||||
Developmental delay | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 58/58 (100%) | 67/67 (100%) |
Hypotonia | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 25/25 (100%) | 34/34 (100%) |
Hypopigmentation | + | + | − | − | + | + | + | + | + | 7/9 (78%) | 65/67 (97%) | 72/76 (95%) |
Cardiomyopathy | + | − | − | − | + | − | + | − | − | 3/9 (33%) | 49/59 (83%) | 52/68 (76%) |
Seizures | + | + | + | + | + | + | + | + | − | 8/9 (89%) | 17/29 (59%) | 25/38 (66%) |
Seizure onset | 1y4m | 2m | 1y10m | 5m | 1y5m | 1y5m | 5m | 1y0m | ||||
Seizure type | Spasm | Spasm | Tonic | Tonic | West | Tonic | Spasm | Myoclonic tonic | ||||
Ophthalmologic finding | ||||||||||||
Cataracts | − | − | − | − | − | − | − | − | − | 0/9 (0%) | 48/63 (76%) | 48/72 (67%) |
Optic disc pallor or atrophy | − | − | − | − | + | − | − | + | − | 2/9 (22%) | 9/9 (100%) | 11/18 (61%) |
Erratic eye movement | − | − | − | − | − | + | + | − | − | 2/9 (22%) | NA | 2/9 (22%) |
Nystagmus | − | − | + | + | + | − | + | + | − | 5/9 (56%) | 11/21 (52%) | 16/30 (53%) |
Hypopigmented iris | − | − | − | − | − | − | − | − | + | 1/9 (11%) | 8/10 (80%) | 9/19 (47%) |
Recurrent infection | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 62/64 (97%) | 71/73 (97%) |
Microcephaly | + | − | + | + | + | + | + | − | + | 7/9 (78%) | 43/48 (90%) | 50/57 (88%) |
High-arched palate | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 15/24 (63%) | 24/33 (73%) |
Central nervous system anomalies | ||||||||||||
ACC | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 65/65 (100%) | 74/74 (100%) |
Paucity of white matter | + | − | + | + | + | − | − | + | NA | 5/8 (63%) | 5/6 (83%) | 10/14 (71%) |
Irregularity of the ventricular wall | + | − | + | + | + | + | + | + | NA | 7/8 (88%) | NA | 7/8 (88%) |
Ventricular dilation | + | + | + | + | + | − | + | + | + | 8/9 (89%) | 8/11 (73%) | 16/20 (80%) |
Delayed myelination | − | − | − | − | + | + | − | − | NA | 2/8 (25%) | 4/6 (67%) | 6/14 (43%) |
Pontine hypoplasia | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 5/9 (56%) | 14/18 (78%) |
Hypoplasia of the medulla oblongata | − | − | − | − | − | − | − | − | − | 0/9 (0%) | NA | 0/9 (0%) |
Cerebellar hypoplasia | − | − | + | + | + | − | − | + | NA | 4/8 (50%) | 13/16 (81%) | 17/24 (71%) |
Cerebral atrophy | + | ± | + | + | + | + | − | + | NA | 6/8 (75%) | 5/9 (56%) | 11/17 (65%) |
Probst bundles | − | ± | − | − | − | − | − | − | NA | 0/8 (0%) | 1/4 (25%) | 1/12 (8%) |
Elevated CK | + | + | + | + | − | + | − | + | + | 7/9 (78%) | 11/13 (85%) | 18/22 (82%) |
Elevated AST/ALT | + | + | + | + | + | + | + | + | + | 9/9 (100%) | 12/13 (92%) | 21/22 (95%) |
Abnormal immunology | − | − | − | − | + | + | − | − | − | 2/9 (22%) | 15/23 (65%) | 17/32 (53%) |
Abnormal muscle biopsy | − | NA | − | − | NA | − | NA | NA | NA | 0/4 (0%) | 20/21 (95%) | 20/25 (80%) |
F = female, M = male, ACC = agenesis of the corpus callosum, NA = not available, CK = creatine kinase, AST = aspartate transaminase, ALT = alanine transaminase, aPatient 2.1 died at the age of 14 years due to respiratory arrest. bPatient 5.1 died at the age of one year due to cardiomyopathy.