Nabais Sá-de Vries syndrome (NSDVS) is a rare disease caused by a heterozygous mutation in the SPOP gene (17q21), which is involved in protein degradation via the ubiquitin-proteasome pathway. Different germline variants within this gene cause two distinct phenotypes (allelic heterogeneity) that affect multiple organs and systems (pleiotropy). These variants are clinically associated with intellectual disability, neurological disorders, and dysmorphic features that exhibit variable expressivity. Here, we present the case of a five-year-old girl who was conceived through assisted reproductive technology. She is the second twin of a dichorionic dizygotic pregnancy. A medical genetic evaluation was initiated at one week of age due to congenital heart disease. She presents with a fronto-parieto-occipital hemangioma, downslanting palpebral fissures, synophrys, retroauricular pits, a depressed nasal bridge, anteverted nares, midface retrusion, a high palate, a micrognathia, an inguinal hernia, bilateral single transverse palmar creases, and a congenital melanocytic nevus. She currently has delayed neurodevelopment and language acquisition, as well as microcephaly, low weight and height, and normal hearing. Exome sequencing revealed a heterozygous missense variant: NM₀01007228. 2 (SPOP): c. 351G>T (p. Met117Ile). In silico testing classifies this variant as likely pathogenic with protein gain of function, which confirms the diagnosis of NSDVS type 1. This case report of a Mexican girl contributes to the expansion of the phenotypic spectrum of NSDVS and supports the implementation of improved multidisciplinary follow-up for affected patients.
Olivares-Huerta et al. (Tue,) studied this question.