Familial agnathia‐holoprosencephaly

Abstract

Two stillborn sisters had characteristics of both agnathia and holoprosencephaly. Familial occurrence implies that agnathia-holoprosencephaly may be determined by a single recessive gene, something to be taken into account when counseling such families. Evidence from human experience and various animal models suggests that agnathia-holoprosencephaly represents a causally heterogeneous single developmental field defect. Anatomical studies of these two stillborn sisters support the view that they shared a developmental field defect which affected structures in the face, cranial cavity, and upper neck. The pathogenesis of these variably expressed defects probably relates to defects in neural crest cells of cranial origin and/or to underlying mesodermal support elements of these cells.

A case of agnathia, tetramelia and diaphragmatic hernia at 18 weeks' gestation

“…There was no history of exposure to drugs or any known teratogenic agent and the karyotype was normal. Autosomal inheritance has been suggested for agnathia-holoprosencephaly 12 , but no anomalies of the central nervous system were present in this fetus and the mother's family history was unremarkable. Other than agnathia, there were no other craniofacial anomalies that would suggest a defect of the ventral portion of the first branchial arch, as occurs in otocephaly.…”

Otocephaly: a case report

“…Although not well understood, otocephaly is thought to be the result of an arrest in the development of the first branchial arch. 1 Wright on his study on guinea pigs described a spectrum of severity in the phenotype seen within the same sibships, ranging from small mandible to agenesis of mandible with severe defect of eye, nose and brain. This implicated a common genetic cause for nonsyndromic dysgnatia and agnatia-prosencephaly.…”

“…21,22 Key to diagnosis are low set or midline position of ears but visualisation of this feature is difficult using 2D ultrasound. 5 Several authors had reported that diagnosis can only be achieved in third trimester, 1,4 Agnatiaotocephaly is probably one of the diagnosis where 3D ultrasound helps in demonstrating the position and shape of ears in addition to facial features. 17,23 Prenatal sonographic detection of fetal polyhydramnios is frequent in association with otocephaly but only detected in third trimester of pregnancy.…”

“…1 Agnathia-otocephaly is considered to be the most severe form of first branchial arch malformation. 2 The estimated prevalence of otocephaly is less than 1 in 70,000 newborn infants.…”

Maternal Diet Supplementation with Methyl Donors and Increased Parity Affect the Incidence of Craniofacial Defects in the Offspring of Twisted gastrulation Mutant Mice

“…The combination of jaw defects and HPE in humans is referred to as agnathia-HPE complex (or dysgnathia-otocephaly; OMIM no. 202650) (19). In Twsg1 2/2 mice, these defects have incomplete penetrance and variable expressivity (18,20).…”