Search for ReCQL4 mutations in 39 patients genotyped for suspected Rothmund–Thomson/Baller‐Gerold syndromes

Abstract

Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the numbers of known genes remain low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type poikiloderma with neutropenia, hereditary sclerosing poikiloderma, and craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with poikiloderma, as well as BGS without poikiloderma.

Nationwide survey of Baller-Gerold syndrome in Japanese population

“…Piard et al reported that no RECQL4 mutations were found in their BGS group without poikiloderma. However, our patient had café-au-lait-like spots but not poikiloderma (8). The relationship between poikiloderma and RECQL4 gene mutation should be further examined.…”

“…This rarity of BGS makes its diagnosis difficult in some cases. Piard et al (8). Showed that the mean age at referral for BGS was 7 years.…”

Role of Pediatric Geneticists in Craniofacial Teams: The Identification of Craniofacial Conditions with Cancer Predisposition

“…Rothmund-Thomson syndrome carries an increased risk for skin cancer, osteosarcoma and lymphoma. 9 Patient 4 was born with a cleft palate, micrognathia, and ocular hypertelorism. She had poor oromotor skills and mild deficits in motor development as she rolled at 8 months, sat at 10 months, and walked at 18 months.…”

“…Piard et al, 9 Rathi et al, 42 Siitonen et al, 43 Van Maldergem et al, 44 48 1978 Note: Table III notes cancer predisposition syndromes that may have craniofacial features that could trigger early referral to a craniofacial team before other symptoms are evident. The craniofacial manifestations are not seen in all patients and may be variable or absent.…”

Estudo genético-clínico de pacientes com síndromes progeróides

“…Wang et al (2001). Esta positividade está de acordo com os dados da literatura, mostrando uma positividade que varia entre 40 e 60% (SUTER et al, 2016;PIARD et al, 2015;SIITONEN et al, 2009;CABRAL et al, 2008 (ZHANG et al, 2016;SUTER et al, 2016;PIARD et al, 2015;FRADIN et al, 2013;SIMON et al, 2010;SIITONEN et al, 2009;CABRAL et al, 2008;SZNAJER et al, 2006;KELLERMAYER et al, 2005;BEGHINI et al, 2003). (Wang et al, 2003).…”