Adult-Onset Craniotubular Dysplasia, Ikegawa Type: A Report of a Case From Bahrain With a Novel Compound Heterozygous TMEM53 Mutation and Literature Review

Craniotubular dysplasia, Ikegawa type (CTDI), is an ultra-rare sclerosing bone disorder associated with pathogenic mutations in the TMEM53 gene. The condition disrupts the negative regulation of ossification, leading to progressive skeletal abnormalities, short stature, and early-onset visual impairment secondary to optic nerve compression. Since its initial description in 2021, only a limited number of cases have been reported, nearly all presenting in childhood. Adult-onset disease remains exceptionally rare and poorly characterized. In this report, we describe a 38-year-old Bahraini gentleman with a 10-year history of progressive left-sided numbness, severe musculoskeletal and back pain, gait disturbance, and unilateral blindness. His presentation was insidious with a gradual neurological decline and predominant spinal manifestations attributable to spinal pathology, which is an atypical presentation compared to previously reported cases that primarily presented with craniofacial involvement. Magnetic resonance imaging (MRI) demonstrated long-segment cervical canal stenosis with spinal cord compression and edema, Schmorl’s nodes, thoracic disc bulges, and lumbar canal stenosis. Despite undergoing two spinal decompression surgeries, his neurological symptoms persisted. Comprehensive genetic evaluation, including whole-exome sequencing, identified two novel rare missense variants in TMEM53 (p.Ala145Pro and p.Pro211Thr) in a compound heterozygous state, establishing the diagnosis of craniotubular dysplasia, Ikegawa type (CTDI), and expanding its allelic spectrum. This case broadens both the phenotypic and genotypic spectrum of CTDI. It provides the most detailed spinal imaging description of this disorder to date and highlights an unusual adult-onset presentation with predominant spinal involvement and unilateral blindness.