Rare Maternal Structural Mosaicism as a Familial Cause of 18p Deletion Syndrome: Cytogenetics Mechanisms and Phenotypic Variability

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The chromosome 18p deletion (18p-) syndrome or monosomy of 18p is a rare chromosome abnormality, considered a contiguous gene deletion syndrome resulting from the deletion of a portion or most of the whole short arm of chromosome 18. Therefore, it can present a spectrum of phenotypes associated with different prognostic outcomes. Understanding the clinical variability of this condition is important once the fertility is preserved, impacting genetic counseling and reproductive outcomes. The aim of this article is to report a case of familial 18p deletion syndrome and its striking phenotypic variability within the same family. A male stillborn presenting alobar holoprosencephaly and his mother who presented with a single central incisor came to our attention for genetic investigation. Karyotype analysis and Fluorescent In Situ Hybridization (FISH) from a cordocentesis blood sample of the male stillborn was performed. Parents’ cytogenetic analyses were obtained through peripheral blood cultures. Chromosomes were analyzed after GTG banding. FISH technique was carried out on both the proband's and maternal samples using WCP18 (whole chromosome 18) specific probes, according to the manufacturer's protocols. The stillborn karyotype and FISH analysis revealed a deletion characterized by 46, XY del(18)(p11.1→pter).ish del(18)(p11.1→pter)(wcp18-). His mother showed the same deletion in 45% of the analyzed cells revealing a rare structural mosaicism. The striking phenotypic variability encountered in this family could be attributed to a genetic combination of the deleted segment in the proband; and the presence of a mosaic normal karyotype may very well attenuate the mother’s phenotypic presentation. The origin of an abnormally structural chromosome in mosaic possibly originated from a post-zygotic cell division event during the embryonic development of the mother. The consequences on the family offsprings of such rare cytogenetic event impacts greatly the family genetic counseling