Objective:

To present an unusual case of a young male with both SCN1a and PNPT1 mutations. 

Background:

The spinocerebellar ataxias (SCAs) are a group of largely autosomal dominant neurodegenerative disorders. SCA25 is a rarer variant, characterized by ataxia, concurrent sensory neuropathy, and gastrointestinal symptoms. Recently, the culprit mutation for the SCA25 variant has been identified in the PNPT1 gene. There has been no prior description of an association between the SCN1a mutation, a well-known mutation responsible for a spectrum of epilepsy disorders including Dravet syndrome, and SCA25.  

Design/Methods:

Retrospective case review

Results:

A 19-year-old male presented with progressive coordination difficulties for 12 years. He met all his developmental milestones until age 7 when family noticed he started to have slower speech and imbalance, leading to falls. He also experienced worsening dizziness and occasional migraine-type headaches. An MRI brain was obtained showing cerebellar atrophy in the vermis and cerebellar hemispheres and he was diagnosed with SCA. At age 10, he developed generalized seizures (tonic stiffening and absence in semiology) that began to increase in frequency. He received extensive genetic testing showing that he had an SCN1a mutation and PNPT1 mutation. Family history is only significant for migraines in the patient’s mother. Since diagnosis, he persistently exhibits ataxia with speech, limb, and gait coordination in addition to overshooting saccades. He has areflexia in all extremities and does not demonstrate tremor, bradykinesia, or sensory deficits.  

Conclusions:

This case illustrates the presentation of an individual with both the PNPT1 (associated with SCA25) and SCN1a mutation. There is no data in the literature demonstrating how often these mutations occur concurrently. The question of how much of this patient’s phenotype is attributed to one of these mutations or both is unknown.