Clinical, Radiological and Molecular Genetic Findings in Six New Cases with Rothmund–Thomson Syndrome: Evidence for a Founder RECQL4 Variant

Abstract Rothmund–Thomson syndrome is a rare autosomal recessive genodermatosis characterized by poikiloderma, growth retardation, juvenile cataracts, congenital anomalies, and skeletal defects. Rothmund–Thomson syndrome type 2 is caused by biallelic mutations in the RECQL4 gene, leading to DNA repair deficiency and cancer predisposition. We report six pediatric patients from three unrelated families carrying the same pathogenic variant associated with Rothmund–Thomson syndrome type 2. All patients exhibited poikiloderma, facial telangiectasia, skin atrophy, growth retardation, microcephaly, and learning difficulties. Trunk was spared. One patient had hearing loss; another was diagnosed after the appearance of facial lesions, following chronic diarrhea and malnutrition. Osteopenia and metaphyseal growth lines were common on radiographs. Rothmund–Thomson syndrome was diagnosed based on clinical and radiological features. RECQL4 sequencing revealed a homozygous pathogenic c.2415_2419del (p.Gly806_Arg807delinsTer) variant in four patients, and compound heterozygosity with the same variant and a novel pathogenic c.1663_1664del (p.Ser555GlyfsTer27) variant in two siblings. Rare DNA repair disorders should be considered in the differential diagnosis of genodermatoses, especially when accompanied by growth retardation and microcephaly. Our findings highlight the value of combining dermatological, radiological, and molecular assessments for accurate diagnosis and counseling. The recurrence of the same variant in unrelated families from one region suggests a founder effect.