A Report of Dual Presentations of Pseudo-Torch Syndrome 1 and Mcc2 Deficiency and Review of the Literature Publisher



A Talea ALI ; S Bayat SHIVA ; Gs Khan Golazin SHAHBODAGH ; N Pak NEDA ; S Azizahari SOLMAZ ; R Sinaei ROYA ; Ar Tavasoli Ali REZA ; M Reza Ashrafi MAHMOUD ; M Heidari MORTEZA
Source: Molecular Syndromology Published:2025

Abstract

Introduction: Pseudo-TORCH syndrome, named as such due to the mimicry of intrauterine TORCH infections in the absence of infection, is a neurological disorder presenting primarily with congenital microcephaly, intracranial calcifications, simplified gyration and polymicrogyria, and severe developmental delay, which can be attributed to variants in the OCLN gene. MCC2 deficiency, a neurometabolic disorder due to impairments in the catabolism of Leucine, with highly variable clinical presentations in addition to landmark metabolic features is put down to variants in MCCC2 gene. Case Presentation: Known as independent conditions, the intriguing presence of dual manifestations in a 3.5-year-old boy was investigated in the study. The patient was referred to our Myelin Disorders Clinic due to congenital microcephaly, developmental regression, and medication-resistant epilepsy. WES was performed on patient’s samples for variant detection and subsequent confirmation. Bioinformatics analysis was performed for prioritization and validation according to the standard criteria. The resultant findings were consequently confirmed in the proband and his parents by Sanger sequencing. WES revealed the presence of two concurrent variants in OCLN and MCCC2 on the same chromosome, chromosome 5, both in homozygous state in the proband. Both variants are classified as pathogenic according to ACMG classification system having been previously reported in the literature. Conclusion: The two variants observed in our patient, a homozygous missense change and a homozygous deletion interestingly occurring on the same chromosome, lead us to think that either these two conditions may be totally independent of each other, having co-occurred by chance, or there may be an underlying association between the two variants, rendering their co-occurrence as a haplotype more possible. © 2025 Elsevier B.V., All rights reserved.