Prenatal diagnosis of micrognathia in 41 fetuses: Retrospective analysis of outcome and genetic etiologies

Abstract

Fetal micrognathia can be detected early in pregnancy. Prognosis of micrognathia depends on the risk of respiratory distress at birth and on the long-term risk of intellectual disability. The purpose of this study was to evaluate the long-term prognosis of fetuses with prenatal diagnosis of micrognathia by estimating the prevalence and the severity of confirmed genetic diagnosis in our cohort. Our retrospective study included 41 fetuses with prenatal diagnosis of micrognathia referred to the multidisciplinary centers for prenatal diagnosis in Nice and Marseille, France, between 2006 and 2016.Fetal micrognathia was associated with cleft palate in 27 cases. A genetic cause was confirmed in 21 cases (67%). A chromosomal abnormality was present in 12 cases, including three copy-number variations diagnosed by array CGH. Monogenic disorders were identified in nine cases, most often after birth. Fetuses with family history of micrognathia or Pierre Robin sequence had a favorable outcome. Prognosis was good for the fetuses without associated findings and normal chromosomal analysis, with the exception of one case with a postnatal diagnosis of mandibulofacial dysostosis with microcephaly. Prognostic was poor for the fetuses with additional ultrasound anomalies, as only 5 out of 28 children had a good outcome. Prenatal diagnosis of micrognathia is an indicator of a possible fetal pathology justifying multidisciplinary management. Our study confirms the necessity of performing prenatal array CGH.Use of high-throughput gene sequencing in prenatal period could improve diagnostic performance, prenatal counseling, and adequate postnatal care.

Epidemiology of Pierre‐Robin sequence in Europe: A population‐based EUROCAT study

“…Prenatal diagnosis of PRS is challenging because micrognathia, retrognathia, and glossoptosis are useful predictors, but not sufficient for a complete diagnosis of PRS, and they can be difficult to find in two dimensional ultrasound 27,28 . Furthermore, micrognathia may appear in association with many other syndromes and structural disorders 29,30 . Ultrasound examination is more efficient in suspected cases of PRS with a family history 18 .…”

Mandibulofacial Dysostosis Guion-Almeida Type: A Syndrome to Recognize in Prenatal

“…In table 2, we collected, in addition to our case, prenatal findings of 6 other fetuses with MFDGA syndrome previously reported in literature [5,8,14,15]. Unfortunately, the cohort is small, and a lot of data is missing that could be related to limitations of the ultrasound examination and the term of pregnancy the US and TOP were done.…”

Imaging of the Fetal Zygomatic Bone

“…15,23 However, a morphologic overlap may exist between the syndromes that constitute first arch syndrome: retrognathia or micrognathia as well as a cleft palate, one of the hallmarks of Pierre Robin sequence, is occasionally present in Treacher Collins syndrome cases. 1,24,25 We suggest classifying cases presenting prenatally with retrognathia or micrognathia according to the status of the zygomatic bones. If the zygomatic bones are visualized, Treacher Collins syndrome is ruled out.…”

“…To date, although 3 genes were identified as causing Treacher Collins syndrome: TCOF1 (treacle ribosome biogenesis factor 1), POLR1C (RNA polymerase I and III subunit C), and POLR1D , a proportion of patients remain without a definitive genetic result, and the diagnosis relies on the clinical phenotype . However, a morphologic overlap may exist between the syndromes that constitute first arch syndrome: retrognathia or micrognathia as well as a cleft palate, one of the hallmarks of Pierre Robin sequence, is occasionally present in Treacher Collins syndrome cases . We suggest classifying cases presenting prenatally with retrognathia or micrognathia according to the status of the zygomatic bones.…”