Novel Compound Heterozygous RECQL4 Pathogenic Variants and Associated Phenotypes in a Chinese Patient With Rothmund-Thomson Syndrome: Case Report and Literature Review.
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BACKGROUND: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, sparse hair, short stature, skeletal abnormalities, and an increased predisposition to malignancies. Pathogenic variants in the RECQL4 gene represent the most common genetic cause of RTS type 2. However, the full phenotypic spectrum, particularly regarding endocrine manifestations, remains incompletely understood. OBJECTIVE: To report novel compound heterozygous RECQL4 pathogenic variant in a Chinese patient, describe a previously unreported endocrine phenotype (gynecomastia), and provide a comprehensive review of the literature regarding the RECQL4 mutational spectrum and differential diagnosis. METHODS: A comprehensive clinical evaluation, including detailed physical examination, dermatoscopic assessment, and histopathological analysis, was performed. Whole-exome and Sanger sequencing were conducted to identify the causative variants. A literature review was additionally performed to contextualize the clinical and genetic findings. RESULTS: A 14-year-old boy presented with classical poikiloderma, short stature, and an unreported feature of gynecomastia associated with low testosterone levels. Genetic testing identified compound heterozygous variants in RECQL4: a known nonsense variant c.2290C>T (p.Glu764*) and a novel frameshift variant c.2053del (p.Asp685Thrfs*5). Our literature review further delineated the differential diagnosis of poikiloderma among related genodermatoses and highlighted the systemic impact of RECQL4 dysfunction. CONCLUSION: The identification of the novel c.2053del variant broadens the known mutational landscape of RECQL4. Furthermore, the integration of our newly observed endocrine phenotype with a literature review underscores the necessity of multidisciplinary evaluation-including endocrinological, orthopedic, and audiological assessments-in the comprehensive management of RTS.