We describe a novel phenotype of unique SPTAN1 mutation identified in two siblings by whole exome sequencing.

SPTAN1 mutations(spectrin alpha, non-erythrocytic 1), are identified to be responsible for Early Infantile Epileptic encephalopathy 5 (EIEE5), a disorder characterized by seizures associated with hypsarrhythmia, profound mental retardation with lack of visual attention and speech development, spastic quadriplegia and hypomyelination of CNS, mostly reported in Japanese.

Two Hispanic daughters of non-consanguineous parents were evaluated for early onset hypotonia and gross motor delays by clinical examination, EMG and muscle biopsy and whole exome sequencing.

Affected siblings ages 4 years and 2 years had severe hypotonia, hyoreflexia, muscle atrophy and global developmental delay. They also had minor facial dysmorphic features including bilateral epicanthal folds, shallow nasal bridge, anteverted nose, mild micrognathia, clinodactyly and extremely narrow feet.

Newborn screening, Mitochondrial testing, karyotyping, methylation analysis, micro array, carnitine profile, serum creatinine kinase  and brain MRI were normal.

EMG showed a non-specific myopathic pattern without any sensorimotor neuropathy. Muscle biopsy showed only slight predominance of Type 1 fibers.

Whole exome sequencing for both siblings showed monoallelic mutation at the SPTAN1 gene (alpha-spectrin), at nucleotide 6319, G>A, resulting in a predicted mutation of ALA2107THR.  This missense mutation occurs in a highly conserved amino acid residue.  Mother did not harbor the mutation.

Over the two years of follow up, children slowly acquired motor skills, but were significantly delayed in acquisition of language.

These siblings have a unique mutation and novel phenotype with generalized weakness, hypotonia and myopathy which has not been previously noted among individuals with SPTAN1 mutations, and are without seizures and or spasticity.