Neuroradiological Phenotype Expansion of the Siddiqi Syndrome: A Case Report

Siddiqi syndrome is a rare autosomal recessive deafness-dystonia disorder caused by pathogenic variants in the FITM2 gene. To date, only 5 unrelated families have been reported in the literature carrying loss-of-function variants in FIMT2 gene. In this report, we describe a 29-year-old woman with compound heterozygous novel variants identified by trio-based exome sequencing. She carries the paternally inherited delins variant c. 158₁61delinsTCAT, p. (Arg53Asn54delinsLeuIle) and the maternally inherited frameshift variant c. 567del, p. (Thr190ProfsTer9) in FITM2 gene. The patient exhibits the main features of the disease, including deafness, intellectual disability, regression of motor skills and poor overall growth. Additionally, she presents with spastic paraplegia which supports recent phenotypic expansion. We describe for the first time, novel brain magnetic resonance imaging signal alterations, not previously associated with this disorder. These neuroimaging findings may provide new insights into the neurological manifestations of Siddiqi syndrome. This case expands the phenotypic and molecular spectrum of FITM2 associated disease and emphasizes the adult-features of this syndrome.