Expanding the genotypic and phenotypic spectrum of the SPTBN4 gene mutation: A new variant and dysmorphology

Abstract

Congenital hypotonia and neuropathy caused by SPTBN4 mutation are the core findings of a newly defined rare syndrome: Neurodevelopmental disorder with hypotonia, neuropathy, and deafness. Although hearing loss secondary to auditory neuropathy, dysmorphic findings, and epilepsy are distinctive features, they are not present in every patient, leading to a wide range of phenotypic spectrum. We report here a male patient with the SPTBN4 gene mutation presenting with core symptoms but not hearing loss and epilepsy. There were also previously unreported dysmorphic findings such as prominent eyebrows, bilateral constant esotropia, microphthalmia, bitemporal narrowing, low hairline, low-set ears, broad nasal bridge, bulbous nose, anteverted nares, and high-arched palate, broadening the phenotypic spectrum even further. In conclusion, both genetic background and phenotypic features of the SPTBN4 mutations were expanded in our report. After exclusion of spinal muscular atrophy in patients with congenital hypotonia and areflexia, the SPTBN4 mutations should be considered.