The following description is based on the publication by Hengel et al. Nat Comm (2020)
Main clinical features include:
- Epilepsy
- variable seizure onset from first few days of life to early childhood
- seizure types include infantile spasms, focal seizures, myoclonic jerks, febrile seizures, generalized tonic-clonic seizures, and atonic seizures
- EEG studies were variably abnormal and patterns included slowed background activity, burst suppression patterns, multifocal spike-wave complexes, and hypsarrhythmia.
- In many patients, seizures remain resistant to therapy, although 2 patients were seizure free on sodium valproate, while 1 showed good response to ketogenic diet.
- Developmental
delay
- Severely impaired motor skills: Most patients were reported to be non-ambulant, however, delayed walking was reported in 2 patients.
- Speech impairment: Most patients were reported to be non-verbal, however, one patient was able to speak in simple phrases at 6yrs of age
- Intellectual disability
- All patients were reported to have moderate to severe intellectual disability
- Hypotonia
- All patients were reported to have hypotonia, especially axial hypotonia. Some patients were noted to develop spasticity of their limbs, dystonia, ataxia or tremor.
- Feeding
difficulties
- Most patients had feeding difficulties, and 60% of patients required tube feeding (naso-gastric or gastrostomy tube). Drooling was also noted in some patients.
- Variable
facial dysmorphism
- Facial features may include protruding ear lobes, ptosis, deep set eyes, epicanthal folds, short flat philtrum, full lower lip and pointed chin.
- Brain imaging showed non-specific findings including delayed myelination enlarged ventricles, cerebral atrophy, cerebellar atrophy, and thin corpus callosum.