Severe Phenotype With RECQL4 Syndrome: A Report of Two Cases

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Baller-Gerold syndrome, RAPADILINO syndrome, and Rothmund-Thomson syndrome are collectively known as RECQL4 syndromes.
• These syndromes are typically inherited in an autosomal recessive manner and primarily affect infants and children.
• Previously, no RECQL4 syndrome phenotypes with a lethal perinatal course had been reported.

Observation:

• This study identified two fetuses presenting with biallelic RECQL4 pathogenic variants during the perinatal period.
• Both fetuses exhibited severe structural abnormalities, including hypoplastic forearms and lower legs.
• One fetus also displayed severe pulmonary hypoplasia, leading to respiratory failure and neonatal death; the other pregnancy was artificially terminated.

Findings:

• Biallelic RECQL4 pathogenic variants were confirmed via exome and Sanger sequencing.
• The identified variants in RECQL4 are associated with a severe, lethal skeletal disorder presenting in the perinatal period.
• This expands the clinical spectrum of RECQL4-related disorders to include lethal perinatal phenotypes.

Implications:

• These findings highlight the potential for RECQL4 pathogenic variants to cause severe, lethal skeletal abnormalities in the perinatal period.
• Early identification and genetic counseling are crucial for families with a history of RECQL4 syndromes.
• Further research into the role of RECQL4 in fetal development may reveal new therapeutic targets.