Phelan-McDermid Syndrome Presenting as a Puzzling Case of Regressive Autism

Phelan-McDermid Syndrome is a genetic neurodevelopmental disorder characterized by intellectual disability, severe speech delay, hypotonia and autism spectrum disorder (ASD). Variable dysmorphic features are also described; the most common of which are large fleshy hands, long eyelashes, pointed chin, prominent/dysplastic ears, bulbous nose, full lips, hypoplastic/dysplastic nails, and dolichocephaly. An associated seizure disorder is relatively common and brain MRIs report variable abnormalities including thinning or hypoplasia of the corpus callosum, generalized white matter atrophy, and nonspecific white matter hyper intensities. Other more common associated features include feeding difficulties with GERD, renal abnormalities such as ureteric reflux and hydronephrosis are considered relatively common [1]. Phelan-McDermid Syndrome is most often caused by a deletion involving chromosome 22q 13.3, a region that includes the SHANK3 gene [2]. Mutations within this gene have also been associated with the Phelan-McDermid phenotype. The SHANK3 gene codes for a protein that appears to be critical in forming postsynaptic connections between neurons as well as being involved in the formation and maturation of the dendritic spines, outgrowths from the dendrites that help connect and transmit nerve impulses. Therefore absence or decreased levels of this protein will lead to impaired neuronal interconnectivity and this is likely to be responsible for the neurodevelopmental outcomes of the Phelan-McDermid Syndrome.