A Revealing Case of SHQ1-Related Neurodevelopmental Disorder: Expanding the Genotypic and Phenotypic Frontier

Abstract

SHQ1-related neurodevelopmental disorder is a rare autosomal recessive condition linked to disrupted ribosome biogenesis, telomerase activity, and RNA modification. Among the few reported cases, typical clinical presentations consist of early-onset hypotonia, seizures, movement disorders, and progressive neurologic impairment. We present a male patient who, at 4 months, displayed global developmental delay, hypotonia, feeding difficulties, and impaired cervical motor control. He progressed to exhibit choreiform movements and oromotor hypotonia. Extensive metabolic and genetic workup was unrevealing; whole exome sequencing (WES) in 2022 was nondiagnostic, and supportive measures were continued. In 2024, WES reanalysis identified compound heterozygous variants in SHQ1, NM_018130.4:c.523G>T (p.Gly175Cys) and NM_018130.4:c.828_831del (p.Glu276fs*12), both now recognized as pathogenic. Brain MRI was normal, and cerebrospinal fluid neurotransmitter analysis revealed reduced homovanillic acid, suggesting dopaminergic pathways. This case expands the clinical spectrum of SHQ1-related disorder by illustrating a milder phenotype with functional developmental gains and emphasis on the diagnostic value of WES reanalysis.