Clinical Insights Into Nabais Sá-De Vries Syndrome due to a Novel SPOP Mutation: Neuromotor, Cognitive, Adaptive,...

Nabais Sá-De Vries syndrome (NSDVS) is an extremely rare autosomal dominant disorder caused by SPOP mutations. To date, only 10 cases have been described presenting with intellectual disability, neurological signs and symptoms, and a variable association of dysmorphic features. In this article, we report a new case of NSDVS involving a novel pathogenic variant of the SPOP gene. We describe the patient's motor, cognitive, adaptive, behavioral, and neurovisual features, as well as her developmental trajectory. The girl, followed-up from the first months of life to 11 years of age, presented with a de novo heterozygous missense in Exon 5 of the SPOP gene (NM_001007228.2:c.361C>T, p.Arg121Trp) and, thus, classified as NSDVS Type 1. Along with a global developmental delay, she showed microcephaly, dysmorphic features (such as narrow forehead, highly arched eyebrows, and blepharophimosis), moderate intellectual disability, adaptive difficulties, language disorder, and several neurovisual signs and symptoms (such as refractive errors, strabismus, nystagmus, altered oculomotor functions and deficits of visual acuity, and contrast sensitivity). These findings suggest a predominant involvement of the central nervous system in NSDVS and expand the phenotypic spectrum of this syndrome.