Is it worth a CGH array? MBD5 haploinsufficiency and clinical variability in MBD5-associated neurodevelopmental disorder: a case report

Background: MBD5 (methyl-CpG-binding domain protein 5) haploinsufficiency is a rare genetic disorder primarily characterized by intellectual disability, speech delay, and various physical and behavioral anomalies. This case is noteworthy due to the presentation of previously unreported symptoms, which contributes to the expanding clinical spectrum of the disorder. Case presentation: We present a 16-year-old girl with a mild phenotype of MBD5 haploinsufficiency, including a clinical history of epileptic seizures responsive to treatment, generalized anxiety, selective mutism, obsessive traits, and aggressive behavior. In addition, she exhibited subclinical hypothyroidism, hyperprolactinemia, and six hypochromic skin spots, which have not been documented in prior literature. She underwent an inconclusive target next-generation sequencing (NGS) of 43 known epilepsy-associated genes. Further investigation using array-CGH revealed a mosaic 407 kb deletion at 2q23.1 encompassing the MBD5 (methyl-CpG-binding domain protein 5) gene. Conclusions: This case emphasizes the role of array-CGH in the diagnosis of cryptogenic cases and the importance of reporting rare Copy Number Variants (CNVs) to refine the phenotypic descriptions of microdeletion/microduplication syndromes.