Clinical, Radiological and Molecular Genetic Findings in Six New Cases with Rothmund-Thomson Syndrome: Evidence for a...

Area of Science:

• Genetics
• Dermatology
• Pediatrics

Background:

• Rothmund-Thomson syndrome (RTS) is a rare genodermatosis with diverse clinical manifestations.
• RTS type 2 results from RECQL4 gene mutations, causing DNA repair defects and cancer susceptibility.

Purpose of the Study:

• To report on six pediatric patients with Rothmund-Thomson syndrome type 2.
• To characterize the clinical, radiological, and molecular findings in these patients.
• To investigate the role of a specific RECQL4 variant.

Main Methods:

• Clinical and radiological assessments of six pediatric patients from three families.
• RECQL4 gene sequencing to identify pathogenic variants.
• Analysis of genotype-phenotype correlations.

Main Results:

• All patients presented with poikiloderma, facial telangiectasia, skin atrophy, growth retardation, and microcephaly.
• RECQL4 sequencing revealed a homozygous pathogenic c.2415_2419del variant in four patients and compound heterozygosity including this variant in two siblings.
• Radiographs showed osteopenia and metaphyseal growth lines.

Conclusions:

• Rare DNA repair disorders like RTS type 2 should be considered in pediatric genodermatoses with growth and developmental issues.
• Integrated dermatological, radiological, and molecular diagnostics are crucial for accurate RTS diagnosis.
• The recurrence of a specific RECQL4 variant suggests a potential founder effect in the studied population.