Expanding the FANCO/RAD51C associated phenotype: Cleft lip and palate and lobar holoprosencephaly, two rare findings in Fanconi anemia

Abstract

Fanconi anemia is a rare chromosome instability disorder with a highly variable phenotype. In the antenatal and neonatal periods, the diagnosis is usually suggested by the presence of typical congenital abnormalities such as intrauterine growth retardation, microcephaly and radial ray defects. We report a newborn female with a prenatal diagnosis of Fanconi anemia, complementation group O (FANCO). Antenatal ultrasounds identified symmetrical intrauterine growth retardation, complex heart defect as well as brain anomalies, overlapping fingers and cleft lip and palate. Imperforate anus was detected after birth. Compound heterozygous RAD51C variants c. [571+5G > A]; [c.935G > A] were detected by prenatal whole exome sequencing and cellular hypersensitivity to DNA interstrand crosslinking agents (DEB, MMC) was confirmed after birth. With only one previously described homozygous RAD51C variant to date, our findings expand the phenotypic spectrum of FANCO and suggest it should be part of the antenatal differential diagnosis for trisomy 13 and 18, due to the presence of atypical findings such as cleft lip and palate, holoprosencephaly, growth restriction and overlapping fingers.

Keywords: Chromosome breakage; FANCO; Fanconi anemia; RAD51C.