Rothmund-Thomson syndrome, a disorder far from solved

Abstract

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a range of clinical symptoms, including poikiloderma, juvenile cataracts, short stature, sparse hair, eyebrows/eyelashes, nail dysplasia, and skeletal abnormalities. While classically associated with mutations in the RECQL4 gene, which encodes a DNA helicase involved in DNA replication and repair, three additional genes have been recently identified in RTS: ANAPC1, encoding a subunit of the APC/C complex; DNA2, which encodes a nuclease/helicase involved in DNA repair; and CRIPT, encoding a poorly characterized protein implicated in excitatory synapse formation and splicing. Here, we review the clinical spectrum of RTS patients, analyze the genetic basis of the disease, and discuss molecular functions of the affected genes, drawing some novel genotype-phenotype correlations and proposing avenues for future studies into this enigmatic disorder.

A family with nine siblings showing signs of Rothmund–Thomson syndrome with two being definitely diagnosed with the syndrome due to homozygous N‐terminal mutation of RECQL4

“…The diagnosis is confirmed when the typical rash is present and/or homozygous pathogenic variants are identified in ANAPC1 , DNA2 , CRIPT , or RECQL4 . 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 There are two subtypes of RTS, RTS1, and RTS2, each with distinct clinical and genetic characteristics. RTS2 is caused by homozygous or compound heterozygous mutations in the RECQL4 gene and is associated with an elevated risk of developing cancer, particularly osteosarcoma.…”