2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Cognitive Decline, Parkinson-like Features, and Mutism lead to Diagnosis of <em>MECP2</em> in a 46 Year Old Male

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A 46-year-old male presented with mental deterioration, rigidity, and cognitive decline. He had a history of mild intellectual disability in childhood, followed by psychiatric decline in his mid-20s. The patient experienced increasing withdrawal, mutism, cognitive and motor regression, and currently exhibited behavior abnormality, limited speech, anxiety, urinary and bowel incontinence, and short stature. The provisional diagnoses of parkinsonism and catatonia were inconclusive. <br /><br />Genetic testing revealed a pathogenic variant in the MECP2 gene, specifically the c.455C>T (p.Ala152Val) variant. This variant has been reported in individuals with intellectual disability, neuropsychiatric symptoms, and movement disorders. The patient's presentation aligned with the phenotypic spectrum of PPM-X syndrome, which includes psychotic disorders, parkinsonism, intellectual disability, macroorchidism, and cognitive regression. His presentation was earlier than other reported males with the same variant and was more similar to a reported female with the variant. <br /><br />This case highlights the importance of considering PPM-X syndrome as a potential diagnosis in individuals with indeterminate psychiatric or parkinson-like features. Genetic testing for MECP2 mutations should be pursued to guide accurate diagnosis and appropriate management. The patient's brother, who also exhibits behavioral and cognitive issues, is suspected of having the same pathogenic variant. If confirmed, their mother would be an asymptomatic carrier. <br /><br />Further research and awareness of MECP2-related phenotypes will contribute to better understanding and identification of these disorders.

Asset Subtitle

Submitter Only - Leslie Dunnington, MS, CGC; Presenting Author - Laura S. Farach, MD;

Meta Tag

Clinical History

Cognitive Disorders

Delineation of Diseases

Genetic Testing

Presenting Author Laura S. Farach, MD

Submitter Only Leslie Dunnington, MS, CGC

Keywords

mental deterioration

cognitive decline

intellectual disability

parkinsonism

catatonia

genetic testing

MECP2 gene

pathogenic variant

PPM-X syndrome

neuropsychiatric symptoms