Complex chromosomal rearrangements causing Langer-Giedion syndrome atypical phenotype: genotype-phenotype correlation and literature review.

ABSTRACT

Langer-Giedion syndrome (LGS) is caused by a deletion of chromosome 8q23.3-q24.11. The LGS clinical spectrum includes intellectual disability (ID), short stature, microcephaly, facial dysmorphisms, exostoses. We describe a 4-year-old girl with ID, short stature, microcephaly, distinctive facial phenotype, skeletal signs (exostoses on the left fibula, coccyx agenesis, stubby and dysmorphic sphenoid bone, osteoporosis), central nervous system malformations (hypoplastic and dysmorphic corpus callosum and septum pellucidum), pituitary gland hypoplasia and hyperreninemia. Array-CGH revealed complex chromosomal rearrangements. A diagnosis of LGS was confirmed by the detection of a 8q23.3-q24.1 deletion. Associated chromosomal abnormalities were a 21q22.1 deletion and a balanced reciprocal translocation t(2;11)(p24;p15) de novo, confirmed by FISH analysis. We document the patient's atypical findings, never described in LGS patients, in order to update the genotype-phenotype correlation. We speculate that the disruption of regulatory elements mapping upstream CYP11B2 involved in the deleted region could cause hyperreninemia.