Severe X-linked chondrodysplasia punctata in 9 new female fetuses.

Fiche publication

Date publication

mars 2015


Membres identifiés du Cancéropôle Est :
Pr VABRES Pierre

Tous les auteurs :
Lefebvre M, Dufernez F, Bruel AL, Gonzales M, Aral B, Saint-Onge J, Gigot N, Desir J, Daelemans C, Jossic F, Schmitt S, Mangione R, Pelluard F, Vincent-Delorme C, Labaune JM, Bigi N, D'Olne D, Delezoide AL, Toutain A, Blesson S, Cormier-Daire V, Thevenon J, El Chehadeh S, Masurel-Paulet A, Joye N, Vibert-Guigue C, Rigonnot L, Rousseau T, Vabres P, Herve P, Lamaziere A, Riviere JB, Faivre L, Laurent N, Thauvin-Robinet C


OBJECTIVES: Conradi-Hunermann-Happle (CDPX2) syndrome is a rare X-linked dominant skeletal dysplasia usually lethal in males while affected females show wide clinical heterogeneity. Different EBP mutations have been reported. Severe female cases have rarely been reported, with only 6 antenatal presentations. METHODS: To better characterize the phenotype in female fetuses, we included 9 antenatally-diagnosed cases of females with EBP mutations. All cases were de novo except for two fetuses with an affected mother and one case of germinal mosaicism. RESULTS: The mean age at diagnosis was 22 weeks of gestation. The ultrasound features mainly included bone abnormalities: shortening (8/9 cases) and bowing of the long bones (5/9), punctuate epiphysis (7/9) and an irregular aspect of the spine (5/9). Postnatal X-rays and examination showed ichthyosis (8/9) and epiphyseal stippling (9/9), with frequent asymmetric short and bowed long bones. The X-inactivation pattern of the familial case revealed skewed X-inactivation in the mildly symptomatic mother and random X-inactivation in the severe fetal case. Differently affected skin samples of the same fetus revealed different patterns of X-inactivation CONCLUSION: Prenatal detection of asymmetric shortening and bowing of the long bones and cartilage stippling should raise the possibility of CPDX2 in female fetuses, especially since the majority of such cases involve de novo mutations. This article is protected by copyright. All rights reserved.


Prenat Diagn. 2015 Mar 9