Phelan McDermid Syndrome: Multiple Sclerosis as a Rare but Treatable Cause for Regression—A Case Report

Abstract

Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the SHANK3 gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. SHANK3 is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation. Individuals with PMcD present with intellectual disability, muscular hypotonia, and severely delayed or absent speech. Further neuropsychiatric manifestations cover symptoms of the autism spectrum, epilepsy, bipolar disorders, schizophrenia, and regression. Regression is one of the most feared syndromes by relatives of PMcD patients. Current scientific evidence indicates that the onset of regression is variable and affects language, motor skills, activities of daily living and cognition. In the case of regression, patients normally undergo further diagnostics to exclude treatable reasons such as complex-focal seizures or psychiatric comorbidities. Here, we report, for the first time, the case of a young female who developed progressive symptoms of regression and a dystonic-spastic hemiparesis that could be traced back to a comorbid multiple sclerosis and that improved after treatment with methylprednisolone.

Molecular Research in Multiple Sclerosis

“…The Special Issue, “Molecular Research in Multiple Sclerosis”, provides a better comprehension of the disease and establishes possible new biomarkers to ensure better care of MS patients in the future. It contains a review of the contribution of metabolomics in MS [ 1 ], the impact of SARS-CoV-2 infection [ 2 ], a review on common microRNAs (miRNAs) in MS and major depression (MD) [ 3 ], the first case of comorbid MS with Phelan McDermid Syndrome (PMcD) with regressive symptoms in a young woman who improved after treatment with methylprednisolone [ 4 ], and a review on intrathecal inflammation in progressive MS [ 5 ].…”

“…Two papers highlight the fact that comorbidities must be considered for disease management [ 3 , 4 ]. Two comorbidities are discussed, namely MD [ 3 ] and PMcD [ 4 ].…”

“…Two papers highlight the fact that comorbidities must be considered for disease management [ 3 , 4 ]. Two comorbidities are discussed, namely MD [ 3 ] and PMcD [ 4 ]. First, MD is present in up to 50% of MS patients and shares abnormalities such as neuroinflammation, peripheral inflammation, gut dysbiosis, chronic oxidative and nitrosative stress, neuroendocrine abnormalities, and mitochondrial dysfunction.…”

“…As an example of the importance of considering MD morbidity in MS management, it was shown that IFN treatment has an incidence rate of depression greater than 0.1, probably due to the interaction between immune, endocrine, and neuronal pathways [ 3 ]. Second, the first case of comorbid MS in PMcD with regressive symptoms, in a young woman who improved after treatment with methylprednisolone, is discussed [ 4 ]. The goal of this paper is to evaluate if the incidence of PMcD and MS is coincidental or if there is a correlation in the pathophysiology, such as the involvement of SHANK3 and IGF1.…”

“…More cases would be needed to confirm these hypotheses. However, this first case shows the importance of additional diagnostics in patients with PMcD with regressive symptoms [ 4 ].…”