Expanding the clinical phenotype of HIST1H1E syndrome: cerebellar atrophy and bilateral optic neuropathy, a case report.

BACKGROUND

HIST1H1E syndrome is caused by frameshift variants in the HIST1H1E gene; while strabismus and refractive errors have been previously reported, this is the first case describing optic and cerebellar atrophy in an affected individual to our knowledge.

METHODS

A 51-year-old woman with intellectual disability, recurrent falls, and progressive visual difficulties required comprehensive ophthalmic, neurologic, and genetic evaluation.

RESULTS

Systemic examination revealed characteristic facial dysmorphism, brachydactyly, ataxic gait, tremor, and positive Romberg's sign. Ophthalmic examination showed bilateral optic disc pallor with patchy visual field deficits. Optical coherence tomography (OCT) confirmed retinal nerve fiber involvement and ganglion cell layer (GCL) loss. Electrophysiology supported bilateral optic neuropathies. Computed Tomography demonstrated optic nerve and cerebellar atrophy. Whole-exome sequencing identified a pathogenic heterozygous variant c.464dupC.p.(Lys157Glufs*39) in the HIST1H1E gene.

CONCLUSION

This patient expands the HIST1H1E syndrome phenotype to include cerebellar and optic nerve atrophy compatible with a neurodegenerative process.