Haploinsufficiency of and in the Foetus with an abnormal facial profile detected in the first trimester of pregnancy.

BACKGROUND

Interstitial microdeletion 14q22q23 is a rare chromosomal syndrome associated with variable defects: microphthalmia/anophthalmia, pituitary anomalies, polydactyly/syndactyly of hands and feet, micrognathia/retrognathia. The reports of the microdeletion 14q22q23 detected in the prenatal stages are limited and the range of clinical features reveals a quite high variability.

CASE PRESENTATION

We report a detection of the microdeletion 14q22.1q23.1 spanning 7,7 Mb and involving the genes and in the foetus by multiplex ligation-dependent probe amplification (MLPA) and verified by microarray subsequently. The pregnancy was referred to the genetic counselling for abnormal facial profile observed in the first trimester ultrasound scan and micrognathia (suspicion of Pierre Robin sequence), hypoplasia nasal bone and polydactyly in the second trimester ultrasound scan. The pregnancy was terminated on request of the parents.

CONCLUSION

An abnormal facial profile detected on prenatal scan can provide a clue to the presence of rare chromosomal abnormalities in the first trimester of pregnancy despite the normal result of the first trimester screening test. The patients should be provided with genetic counselling. Usage of quick and sensitive methods (MLPA, microarray) is preferable for discovering a causal aberration because some of the CNVs cannot be detected with conventional karyotyping in these cases. . Literature review of the genotype-phenotype correlation in similar reports leads us to the conclusion that dosage imbalance of the chromosomal segment 14q22q23 (especially haploinsuffiency of the genes and ) contributes significantly to orofacial abnormalities. Association of the region with the Pierre Robin sequence appears to be plausible.