2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Novel Biallelic Variants in the <em>CSMD1</em> Gene in a Child with Cerebellar Ataxia and Developmental Regression: A Case Report

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This case report describes a child with cerebellar ataxia and developmental regression who was found to have novel biallelic variants in the CSMD1 gene. The patient presented with symptoms including impaired gait, dysarthria, tremor, recurrent headaches, lower limb tingling and pain, fatigue, and behavioral deterioration. The onset of symptoms occurred at 8 years of age following a viral illness. A genetic work-up was pursued due to the sudden and unexplained neurologic degeneration. The patient's phenotype overlapped with four previously reported cases of the same genetic disorder, suggesting that the CSMD1 variants may be the underlying cause for her condition.<br /><br />The presentation of the patient is similar to the other reported cases, with cerebellar ataxia, gait abnormalities, and dysarthria being common features. The patient also had additional symptoms such as behavioral and mood changes, developmental delays, and intellectual impairment, which were similar to Patient 2 in the previous cases. Some minor differences were noted in this case, including lower limb numbness and tingling, fatigue, and headaches, which were seemingly triggered by a viral illness. Morphologic changes were not observed on brain MRI, which is different from the previous cases.<br /><br />Genetic testing revealed biallelic variants in the CSMD1 gene, specifically the variants c.2291C>T (p.Ala764Val) and c.7325G>A (p.Gly2442Asp). These variants involve highly conserved amino acids and have uncertain significance. The patient's case expands the phenotypic spectrum of this genetic disorder, including the potential for normal brain imaging.<br /><br />Overall, this case report highlights the importance of considering CSMD1-related cerebellar ataxia in patients presenting with similar symptoms. Further research is needed to understand the natural history of this genetic condition and its implications.

Asset Subtitle

Presenting Author - Shelby Geilmann, BS; Co-Author - Brian J. Shayota, MD, MPH;

Meta Tag

Brain/Nervous System

Clinical History

Exome sequencing

Genetic Testing

Identification of Disease Genes

Phenotypic delineation of disorders

Variant Detection

Co-Author Brian J. Shayota, MD, MPH

Presenting Author Shelby Geilmann, BS

Keywords

cerebellar ataxia

developmental regression

CSMD1 gene

impaired gait

dysarthria

tremor

headaches

lower limb tingling

fatigue

behavioral deterioration