Expanding the Mutational Spectrum of Rahman Syndrome: A Rare Disorder with Severe Intellectual Disability and Particular Facial Features in Two Chinese Patients.

Abstract Background The study aimed to investigate the clinical and genetic features of Rahman syndrome caused by HIST1H1E gene mutations. Methods We retrospectively analyzed the clinical information and genetic testing results of a Rahman syndrome family in an outpatient clinic in August 2020 and summarized the clinical characteristics of the HIST1H1E gene mutations in conjunction with peer‐reviewed reports. Results A 4‐year‐old boy was diagnosed with severe developmental delay and with specific features (large head, full cheeks, high hairline, low‐set ear, sparse eyebrows, and short neck) similar to his mother (mild intellectual disability, high hairline, reduced hair, ptosis, sagging skin, and hyperkeratosis) and premature aging. Trio whole exome sequencing (WES) revealed a novel maternal c.368dup (p.G124Rfs*72) heterozygous mutation in the HIST1H1E gene. There have been only a few reported cases with mainly de novo mutations. Only six peer‐reviewed articles in English and one in Chinese have been published regarding this syndrome. From 48 children with Rahman syndrome, 21 were males and 27 were females encompassing 25 mutations in the HIST1H1E gene. All mutations located in C‐terminal tail were frameshift mutations leading to premature protein termination. Conclusion Rahman syndrome, caused by the HIST1H1E gene mutation, is a rare autosomal dominant disorder in which the patient has an unusual facial appearance with high hairline and full cheeks, and clinical manifestations of mild to severe intellectual disability, motor delay and speech delay. Genetic testing may assist in the diagnosis of these patients. This diagnosis will permit early speech rehabilitation to improve their quality of life.