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Journal of Anatomy Jan 1924
PubMed: 17104005
DOI: No ID Found -
Genes Dec 2022Agnathia-otocephaly complex (AOC) is a rare and usually lethal malformation typically characterized by hypoplasia or the absence of the mandible, ventromedial and caudal...
Agnathia-otocephaly complex (AOC) is a rare and usually lethal malformation typically characterized by hypoplasia or the absence of the mandible, ventromedial and caudal displacement of the ears with or without the fusion of the ears, a small oral aperture with or without a tongue hypoplasia. Its incidence is reported as 1 in 70,000 births and its etiology has been attributed to both genetic and teratogenic causes. AOC is characterized by a wide severity clinical spectrum even when occurring within the same family, ranging from a mild mandibular defect to an extreme facial aberration incompatible with life. Most AOC cases are due to a de novo sporadic mutation. Given the genetic heterogeneity, many genes have been reported to be implicated in this disease but to date, the link to only two genes has been confirmed in the development of this complex: the orthodenticle homeobox 2 () gene and the paired related homeobox 1 () gene. In this article, we report a case of a fetus with severe AOC, diagnosed in routine ultrasound scan in the first trimester of pregnancy. The genetic analysis showed a novel 10 bp deletion mutation c.766_775delTTGGGTTTTA in the gene, which has never been reported before, together with a missense variant c.778T>C in cis conformation.
Topics: Pregnancy; Female; Humans; Genes, Homeobox; Craniofacial Abnormalities; Jaw Abnormalities; Abnormalities, Multiple; Homeodomain Proteins; Otx Transcription Factors
PubMed: 36553536
DOI: 10.3390/genes13122269 -
Molecular Syndromology Sep 2013Otocephaly-dysgnathia complex is characterized by mandibular hypo- or aplasia, ear abnormalities, microstomia, and microglossia. Mutations in the orthodenticle homeobox...
Otocephaly-dysgnathia complex is characterized by mandibular hypo- or aplasia, ear abnormalities, microstomia, and microglossia. Mutations in the orthodenticle homeobox 2 (OTX2) and paired related homeobox 1 (PRRX1) genes have recently been identified in some cases. We screened 4 otocephalic cases for these 2 genes and identified OTX2 mutations in 2 of them, thus confirming OTX2 is implicated in otocephaly. No PRRX1 mutation was identified. Interestingly, ocular involvement is not a constant feature in otocephalic cases with an OTX2 mutation. In one case, the mutation was inherited from a microphthalmic mother. The mechanism underlying this intrafamilial phenotypic variability remains unclear, but other genetic factors are likely to be necessary for the manifestation of the otocephalic phenotype.
PubMed: 24167467
DOI: 10.1159/000353727 -
BMJ Case Reports Aug 2017Cyclopia is a rare form of lethal holoprosencephaly (HPE) due to incomplete cleavage of prosencephalon during embryogenesis, leading to failure of the orbits of the eye...
Cyclopia is a rare form of lethal holoprosencephaly (HPE) due to incomplete cleavage of prosencephalon during embryogenesis, leading to failure of the orbits of the eye to divide into two cavities. We report two cases, one with cyclopia and another case of cyclopia with agnathia-otocephaly complex (AOC). AOC (also known as agnathia-microstomia-synotia syndrome) is a rare lethal congenital malformation of the first branchial arch characterised by the association of agnathia (agenesis of mandible) or mandibular hypoplasia, melotia (anteromedial malposition of ears), microstomia (small mouth), aglossia or microglossia (absent or rudimentary tongue). These two reported cases had in common a single eye and alobar HPE. The first case was live born and the second stillborn. Both mothers did not have antenatal care.
Topics: Craniofacial Abnormalities; Ear, External; Female; Holoprosencephaly; Humans; Infant, Newborn; Jaw Abnormalities; Live Birth; Microstomia; Stillbirth
PubMed: 28855214
DOI: 10.1136/bcr-2017-220159 -
Case Reports in Obstetrics and... 2016Agnathia is a rare disease characterized by the absence of a mandible. Few cases of prenatally diagnosed isolated agnathia have been reported. We present a case report...
Agnathia is a rare disease characterized by the absence of a mandible. Few cases of prenatally diagnosed isolated agnathia have been reported. We present a case report and review of the literature of prenatally diagnosed agnathia. A 38-year-old woman (gravida 0, para 0) was referred to our hospital at 28 weeks and 3 days of gestation for fetal evaluation because of polyhydramnios and suspected facial anomalies. Three-dimensional ultrasonography and MRI indicated agnathia. Premature rupture of the membranes occurred before the parents could reach a decision on the postnatal treatment. We performed emergency cesarean section on the second day of the 33rd week of gestation. The neonate was deemed nonresuscitable and he died of airway obstruction shortly after birth. Because agnathia is associated with very poor prognosis, accurate prenatal diagnosis and detailed counseling should be promptly provided before unexpected delivery to the parents for the determination of postnatal treatment.
PubMed: 27579201
DOI: 10.1155/2016/8512351 -
The American Journal of Case Reports May 2023BACKGROUND Agnathia-otocephaly complex (AOC) is a rare congenital malformation due to a first-branch arch disorder and has been considered lethal. However, milder...
BACKGROUND Agnathia-otocephaly complex (AOC) is a rare congenital malformation due to a first-branch arch disorder and has been considered lethal. However, milder variants of the isolated type of AOC have been reported as nonlethal. The ex-utero intrapartum treatment (EXIT) procedure is basically indicated for a fetus with a high risk of airway obstruction immediately after birth; it is not indicated for all AOC cases but is chosen to treat cases until the airway can be evaluated to achieve a better prognosis. CASE REPORT A 37-year-old woman was referred with reported fetal facial deformity and polyhydramnios at 27 weeks of gestation. Our fetal ultrasound scans showed agnathia, microstomia, and synotia, but not holoprosencephaly. Isolated AOC was diagnosed prenatally. Magnetic resonance imaging and microbubble tests revealed delayed fetal lung maturation, although it was not completely unmatured. With patient agreement, an emergency cesarean section with EXIT was performed because of clinical chorioamnionitis at 35 weeks of gestation. Tracheostomy was attempted for 16 min during EXIT and was completed 4 min after delivery. Despite this, the neonate died 12 h after delivery from severe respiratory failure and a tension pneumothorax caused by a hypoplastic lung. CONCLUSIONS There is controversy surrounding the non-lethality of all isolated AOC cases and the non-contraindication of EXIT procedures. Our case was estimated as the milder variant, and the EXIT procedure was indicated; however, the neonate died of the hypoplastic lung. The evaluation methods of lung maturation are inconsistent, and the indication of the invasive EXIT procedure must be carefully considered.
Topics: Infant, Newborn; Humans; Pregnancy; Female; Adult; Cesarean Section; Craniofacial Abnormalities; Airway Obstruction; Ultrasonography, Prenatal
PubMed: 37165610
DOI: 10.12659/AJCR.939016 -
The Journal of Biological Chemistry Oct 2007A palmitate linked to the inositol in glycosylphosphatidylinositol (GPI) is removed in the endoplasmic reticulum immediately after the conjugation of GPI with proteins...
A palmitate linked to the inositol in glycosylphosphatidylinositol (GPI) is removed in the endoplasmic reticulum immediately after the conjugation of GPI with proteins in most cells. Previously, we identified PGAP1 (post GPI attachment to proteins 1) as a GPI inositoldeacylase that removes the palmitate from inositol. A defect in PGAP1 caused a delay in the transport of GPI-anchored proteins (GPI-APs) from the endoplasmic reticulum to the cell surface in Chinese hamster ovary cells, although the cell-surface expression of GPI-APs in the steady state was normal. Nevertheless, in most cells, GPI-APs undergo deacylation. To elucidate the biological significance of PGAP1 in vivo, we established PGAP1 knock-out mice. Most PGAP1 knock-out mice showed otocephaly, a developmental defect, and died right after birth. However, some survived with growth retardation. Male knock-out mice showed severely reduced fertility despite the capability of ejaculation. Their spermatozoa were normal in number, motility, and ability to ascend the uterus, but were unable to go into the oviduct. In vitro, PGAP1-deficient spermatozoa showed weak attachment to the zona pellucida and a severely diminished rate of fertilization. Therefore, an extra acyl chain in GPI anchors caused severe deleterious effects to development and sperm function.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Endoplasmic Reticulum; Female; Glycosylphosphatidylinositols; Heterozygote; Infertility, Male; Male; Membrane Proteins; Mice; Mice, Knockout; Oviducts; Palmitic Acid; Phosphoric Monoester Hydrolases; Protein Processing, Post-Translational; Skull; Sperm Motility; Sperm-Ovum Interactions; Spermatozoa; Uterus; Zona Pellucida
PubMed: 17711852
DOI: 10.1074/jbc.M705601200 -
Canadian Journal of Comparative... Sep 1963Fox, M. W., The Jackson Laboratory, Bar Harbor, Maine. Developmental Abnormalities of the Canine Skull. Prognathism of the upper jaw and partial agnathia of the lower...
Fox, M. W., The Jackson Laboratory, Bar Harbor, Maine. Developmental Abnormalities of the Canine Skull. Prognathism of the upper jaw and partial agnathia of the lower jaw and related disorders including dental anomalies, palatitis, and otocephaly are described. Similarly, secondary or concurrent anomalies associated with brachygnathism are discussed where an excess of soft tissue in proportion to the size of the upper jaw and facial (brachyfacial) area may cause a variety of clinical conditions. The higher incidence of neoplasia of the CNS in brachycephalic dogs may be related to reduction in cranial capacity in proportion to brain volume and pressure changes are less easily compensated in the brachygnathic breeds.
PubMed: 17649461
DOI: No ID Found -
Ultrasound in Obstetrics & Gynecology :... May 1998We report a case of the prenatal diagnosis of a very rare anomaly, namely isolated otocephaly, using two-dimensional and three-dimensional ultrasound at 24 weeks of...
We report a case of the prenatal diagnosis of a very rare anomaly, namely isolated otocephaly, using two-dimensional and three-dimensional ultrasound at 24 weeks of gestation. Two-dimensional ultrasound revealed polyhydramnios, absence of a stomach shadow, hypotelorism and a proboscis-like mass. Three-dimensional ultrasound gave a precise demonstration of the striking craniofacial features of otocephaly including agnathia, synotia, microstomia and protuberance of the nose-mouth fusion. The use of three-dimensional ultrasound provided a whole view of the very rare lethal malformation in utero and contributed significantly to prenatal diagnosis.
Topics: Abortion, Legal; Adult; Craniofacial Abnormalities; Face; Female; Humans; Ultrasonography, Prenatal
PubMed: 9644778
DOI: 10.1046/j.1469-0705.1998.11050361.x -
Journal of Medical Genetics Feb 1982
Topics: Abnormalities, Multiple; Chromosomes, Human; Female; Humans; Infant, Newborn; Karyotyping; Placenta Diseases; Pregnancy
PubMed: 7069754
DOI: 10.1136/jmg.19.1.78