Unilateral Agenesis of the Mandible (Agnathia) in a Fetus with 4p-/10q Duplication Associated with Balanced Paternal Cryptic 4p/10q Translocation: Multidisciplinary Management of a Complex Case

Agenesis of the ramus of the mandible (agnathia) is a rare disease that can be part of more than 100 genetic syndromes. From an embryological point of view, agenesis of the mandible is linked to defects in migration of neural crest cells that determine a developmental anomaly of the first arch or mandibular arch, during the 4th week of embryogenesis [1]. Agnathia can be isolated or commonly associated with holoprosencephaly. Evidence from humans and animal model suggest that agnathia-holoprosencephaly represents a causally heterogeneous single developmental field defect [2]. Agnathia may be usually recognized by ultrasound during the second trimester of pregnancy and may be misinterpreted as micrognathia [3–5]. If micrognathia is the only sonographic finding identified, parents should be awarded for possible respiratory complications at birth, presence of facial clefting, and/or developmental delay [6]. Chromosomal abnormalities have been detected in 66 % of fetuses with micrognathia, in 77 % with macroglossia, in 48 % with cleft lip and palate, in 45 % with severe hypotelorism or cyclops, and in 32 % with nasal hypoplasia, proboscis, or single nostril [4, 7]. Teoh and Meagher [8] have reported a first-trimester (13 weeks) diagnosis of micrognathia and receding chin by using transvaginal ultrasound, with later diagnostic confirmation at 19 weeks’ gestation. These findings were associated with complex cardiac defect and unilateral talipes equinovarus in a fetus with normal karyotype and with a definitive diagnosis of Pierre Robin syndrome. Sepulveda et al. [9] have demonstrated the value of the retronasal triangle view for detecting micrognathia in the first trimester. Absent visualization of the mandibular gap or failure to identify the mandible in coronal view is highly suggestive of micrognathia and should prompt a targeted ultrasound scan to assess for other anomalies. The role of RNT in the early prenatal diagnosis of orofacial clefts has been confirmed later by Tonni et al. [10].