Table 1 Clinical/radiological findings for patients with variants of genes previously implicated in a different neurological phenotype
Patients | P7 | P8 | P9 | P10 | P11 | P12 | P13 |
|---|---|---|---|---|---|---|---|
Country of origin | Tunisia | Tunisia | Tunisia | Morocco | Morocco | Portugal | Morocco |
Sex | F | M | M | F | F | M | F |
HC birth/HC last evaluation (SDS) | 0/−2 | 0/−1.5 | 0/0 | 0/0 | 0/−2 | 0/0 | 0/+0.5 |
First signs | |||||||
Neonatal hypotonia | + | + | + | + | + | − | + |
Motor delay | + | + | + | + | + | + | + |
Other | − | − | − | − | − | Myoclonus at 40 days | Prenatal ventriculomegaly |
Signs at last evaluation | |||||||
Age (years) | 7 | 4 | 5 | 8 | 20 | 20 | 19 |
Head control | + | + | + | + | + | + | + |
Able to sit without support (age in months) | + (12) | + (13) | + (?) | + (13) | + (12) | + (?) | + (?) |
Walking (age in years) | Few steps with support (?) | Few steps with support (?) | Few steps with support (?) | Ataxic frequent falls (3) | Few steps with support (?) | Ataxic (4) | Ataxic (2.2) |
Static ataxia | + | + | + | + | + | + | + |
Dysmetria | + | − | − | + | + | + | + |
Dysarthria | + | + | + | ? | ? | + | + |
Intense tremor | − | − | − | + | − | − | + |
Ophthalmological findings | Abnormal pursuit and nystagmus ERG not performed | Abnormal pursuit and nystagmus ERG not performed | Abnormal pursuit and nystagmus Abnormal ERG, normal fundus | − | − | − | Abnormal pursuit |
Seizures/age at onset | − | − | − | − | Focal seizures/16 years | One febrile seizure/1 year | − |
Spasticity | + | − | − | − | + | − | − |
Neuropathy | − | − | − | + | − | − | + |
Intellectual disability | Severe | Severe | Severe | Severe | Severe | − | Severe |
Other | Stereotypies | − | − | Hypocholesterolemia, hyperkinetic movement disorder | Short stature (-3SDS) | − | Hypocholesterolemia, hyperkinetic movement disorder, alacrymia, behavioral disorder in late teens |
MRI findings | |||||||
Cerebellum | Atrophy (V+H) Hypoplasia (V) | Atrophy (V+H) Hypoplasia (V) | Atrophy (V+H) Hypoplasia (V) | Normal | Atrophy (V>H) | Atrophy (V) | Normal |
Other | − | − | − | − | VM, Reduced volume of WM, thin posterior CC | − | Slight ventriculomegaly |
Gene | BRAT1 | BRAT1 | BRAT1 | NGLY1 | AP4M1 | CACNA2D2 | NGLY 1 |
Variant | NM_152743.3: c.925_930del p.Pro309_Gln310del | NM_152743.3: c.925_930del p.Pro309_Gln310del | NM_152743.3: c.925_930del p.Pro309_Gln310del | NM_018297.3: c.1789G>A p.Asp597Asn | NM_004722.3: c.1137+1G>T p.Ser342Argfs*65? | NM_001174051.2: c.2992G>A p.Asp998Asn | NM_018297.3: c.1789G>A p.Asp597Asn |
Status | hm | hm | hm | hm | hm | hm | hm |
Other neurological phenotypes for the same gene | RMFSL 20 “milder phenotype” (intellectual disability, epilepsy, ataxia and cerebellar atrophy without early death) 21 | AR spastic paraplegia “AR congenital cerebral palsy” 22 | |||||
