Severe Phenotype With RECQL4 Syndrome: A Report of Two Cases

ABSTRACT Baller–Gerold syndrome (BGS, OMIM: 218600), RAPADILINO syndrome (OMIM 266280), and Rothmund–Thomson syndrome (RTS, OMIM 266280), which are caused in some cases by RECQL4 pathogenic variants, show autosomal recessive inheritance. Some refer to them collectively as RECQL4 syndromes. Most cases have been reported during infancy and childhood periods. However, there have been no reports of phenotypes resulting in a lethal course in the perinatal period. We identified two fetuses with biallelic RECQL4 pathogenic variants during the perinatal period. The two fetuses with RECQL4 syndrome showed structural abnormalities, including severely hypoplastic forearms and lower legs. One fetus also had severe pulmonary hypoplasia. One case resulted in neonatal death because of respiratory failure, and the other was artificially terminated during pregnancy. The RECQL4 pathogenic variants were identified by exome sequencing followed by Sanger sequencing. The biallelic RECQL4 pathogenic variants can induce a lethal skeletal disorder.