Phelan–McDermid Syndrome

Phelan–McDermid syndrome (PMS) is a rare genetic syndrome caused by deletions to 22q13.3 or sequence variants of SHANK3. SHANK3 is expressed throughout the body and plays an important role in structuring, maintaining, and facilitating communication at neuronal synapses, as well as regulating circadian transcription factors. The phenotypic presentation of individuals with PMS is highly variable, but is most commonly defined by hypotonia, intellectual disability, impaired expressive language skills, regression or loss of skills, epilepsy or seizures, autistic symptoms, and psychiatric symptoms. Primary care providers play an important role in establishing the initial diagnosis of PMS and should be aware of the common clinical characteristics of the syndrome. Ongoing care for patients with PMS should involve an interdisciplinary team of providers, including neurologists, cardiologists, gastroenterologists, psychologists, and psychiatrists. An evaluation of physical, mental, and developmental functioning should be conducted after a patient receives a diagnosis of PMS, and the patient’s functioning should continue to be monitored over time. Although there is no cure for PMS, psychosocial interventions such as Applied Behavioral Analysis (ABA) therapy, speech therapy, physical therapy, and occupational therapy may be useful in promoting daily living and functional communication skills. Pharmacological treatments such as antiepileptics, antipsychotics, or melatonin, may also be effective in treating certain neuropsychiatric symptoms associated with PMS, such as epilepsy, psychosis, and sleep disruption, respectively. Additional research is needed to fully understand the neurobiological underpinnings of PMS and develop more effective treatments.