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Free keywords:
Abnormalities, Multiple/diagnostic imaging/*genetics
Brachydactyly/diagnostic imaging/*genetics/physiopathology/surgery
Child
Chromosome Deletion
Chromosome Duplication
Chromosomes, Human, Pair 2/*genetics
Diabetes, Gestational/genetics/physiopathology
Female
Femur/*abnormalities/diagnostic imaging/physiopathology/surgery
Histone Deacetylases/genetics
Humans
Pierre Robin Syndrome/diagnostic imaging/*genetics/physiopathology/surgery
Pregnancy
Repressor Proteins/genetics
Risk Factors
Hacns1
array-CGH
de novo complex genomic rearrangement
femoral facial syndrome (FFS)
femoral hypoplasia unusual face syndrome (FHUFS)
limb enhancer element 921
Abstract:
The femoral facial syndrome (FFS) is a rare congenital anomaly syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism. The etiology of FFS is currently unknown but maternal/gestational diabetes has been proposed as a strong risk factor for syndromic femoral hypoplasia. In affected children born to non-diabetic mothers, a genetic contribution to FFS is suspected; however, no chromosomal anomalies or gene mutations have been identified so far. Here, we report on a girl with FFS and a de novo complex chromosome rearrangement of terminal chromosome 2q37.2. Radiographs of the pelvis and lower limbs showed bilateral shortening and bowing of the femur and radiographs of hands and feet revealed a brachydactyly type E (BDE). Using high resolution array-CGH, qPCR, and FISH, we detected a ~1.9 Mb duplication in the chromosomal region 2q37.2 and a ~5.4 Mb deletion on chromosome 2q37.3 that were absent in the parents. The duplication contains six genes and the deletion encompasses 68 genes; the latter has previously been shown to cause BDE (through haploinsufficiency for HDAC4) but not femoral hypoplasia. Therefore, we propose that the duplication 2q37.2 could be causative for the femur phenotype. To the best of our knowledge, our report is the first to propose a genetic cause in a case of FFS.
