SUZ12 variant identified as a genetic cause of overgrowth phenotype and spinal stenosisGenetic variant linked to spine issues in overgrowth syndrome

ObjectiveTo expand the phenotypic and genotypic spectrum of Imagawa-Matsumoto syndrome (IMMAS) by investigating the genetic etiology and unique clinical manifestations of an overgrowth case associated with a SUZ12 gene variant.MethodsWe report a case of IMMAS in an 11-year-old Chinese girl who was admitted to our hospital due to unsteady gait and an abnormal walking pattern for 1.5 years. Trio-based whole-exome sequencing (trio-WES) was performed to identify the genetic etiology. Additionally, we conducted a systematic literature review of previously reported cases of overgrowth syndromes associated with SUZ12 variants.ResultsThe patient presented with generalized overgrowth, characteristic facial features, and skeletal abnormalities consistent with IMMAS. Cervical spine magnetic resonance imaging (MRI) revealed cervical canal stenosis accompanied by signs of cervical spinal cord compression and cord edema. The patient underwent posterior cervical single-door decompression, canal expansion with internal fixation, and adhesiolysis of the spinal cord and nerve roots. Trio-WES identified a de novo variant in SUZ12 (NM_015355.4, c.1783_1786del; p. Lys595Profs*18). The literature review suggested that cervical spinal stenosis in our case may represent a newly reported phenotype associated with SUZ12 variants.ConclusionOur findings expand the phenotypic and genotypic spectrum of IMMAS. For patients with overgrowth syndromes, spinal stenosis should be considered during clinical evaluation.