A patient with Phelan‐McDermid syndrome and dilation of the great vessels

Phelan‐McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by a 22q13 deletion. It is characterized by hypotonia, intellectual disability, autistic behaviors, delayed or absent speech, and dysmorphic facial features. Anomalies in other organ systems have been described, requiring neurologic, endocrine, renal, cardiac, and gastrointestinal assessment and monitoring. Here, we present a patient with a karyotype diagnostic of PMS with a previously undescribed finding of progressive dilation of the great arteries. While congenital heart defects have been identified in patients previously, dilation of the great arteries has not been described to our knowledge. SHANK3 haploinsufficiency is understood to be the primary molecular basis for the neurobehavioral phenotype of PMS. Transcripts of the SHANK3 gene have been found outside of the brain, including the heart, suggesting that SHANK3 deletion may contribute to other organ system abnormalities. However, the mechanism of our patient's progressive vascular dilatation is less clear and may have an alternate genetic explanation. Increased cardiac surveillance in patients with 22q13 deletion syndromes may be warranted. Phelan‐McDermid syndrome (PMS), or 22q13 deletion syndrome, is a rare neurodevelopmental disorder characterized by hypotonia, intellectual disability, autistic behaviors, delayed or absent speech, and dysmorphic facial features (Phelan et al, 2001)1. The prevalence is unknown, but it is likely underdiagnosed.2 Neurologic, endocrine, renal, cardiac, and gastrointestinal anomalies require evaluation and surveillance, in addition to monitoring for the risk of recurring infections, dental and vision problems, and lymphedema.3 SHANK3 is the primary implicated gene in PMS, with the loss of one functional copy through a terminal 22q13 deletion, ring chromosome, or unbalanced translocation resulting in a heterogenous phenotype.2 About 75% of cases are the result of simple deletions and 25% are structural rearrangements.4 SHANK3 encodes proline‐rich synapse‐associated protein 2 (ProSAP2), a scaffolding protein in the postsynaptic density of glutamatergic synapses, which is preferentially expressed in the cerebral cortex and cerebellum, but has also been found in other tissues, including the heart.2 The loss of one functional copy of SHANK3 results in disruption of excitatory synaptic function, hence its association with the intellectual disability and speech deficits of PMS.3, 5 Here, we describe a patient with a 22q13 deletion (including SHANK3) and a phenotype demonstrating typical features of PMS, but with the previously undescribed finding of dilation of the great arteries. This unique case may point to an alternate genetic explanation for the cardiovascular abnormalities seen in PMS and the need for closer cardiac surveillance.