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Ultrasound in Obstetrics & Gynecology :... Aug 2003
Topics: Abnormalities, Multiple; Adult; Craniofacial Abnormalities; Eye Abnormalities; Female; Fetal Diseases; Humans; Magnetic Resonance Imaging; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 12905522
DOI: 10.1002/uog.135 -
Journal of Oral and Maxillofacial... Jul 2003
Topics: Branchial Region; Ear, External; Female; Humans; Infant, Newborn; Mandible; Microstomia; Syndrome
PubMed: 12856261
DOI: 10.1016/s0278-2391(03)00160-5 -
American Journal of Medical Genetics.... Jun 2003
Topics: Abnormalities, Multiple; Adult; Diseases in Twins; Ear; Female; Holoprosencephaly; Humans; Jaw Abnormalities; Male; Pregnancy; Twins, Monozygotic
PubMed: 12784314
DOI: 10.1002/ajmg.a.20073 -
American Journal of Medical Genetics Dec 2002Ever more frequent and closer involvement by clinical geneticists and counselors in the prenatal assessment of development mandates a better understanding of all stages... (Review)
Review
Ever more frequent and closer involvement by clinical geneticists and counselors in the prenatal assessment of development mandates a better understanding of all stages of human ontogeny, but especially those of earliest development during which most of the lethal and all of the gross, multiple and complex defects of morphogenesis arise. Because of the phenomenon of universality, i.e., identical molecular inductive mechanisms involved in the process of embryonic pattern formation in all vertebrates, experimental animals indeed are a most valuable approach to an understanding of the causal and formal aspects of development and are beginning to forge essential, strong bonds between molecular biologists and clinicians in a mutually supportive discipline of developmental biology. However, to grieving parents of a stillborn fetus with, say, Pentalogy of Cantrell, sirenomelia or otocephaly, mouse data offer little comfort or reassurance about recurrence; thus, it is imperative to make ever more effective a science of human teratology (sensu lato) with participating reproductive geneticists, obstetricians, neonatologists, ultrasonographers, pediatric/fetal pathologists, cytogeneticists and pediatric geneticists to generate the diagnostic, pathogenetic and causal data necessary to counsel and to comfort the parents. Few molecular data exist on causes of blastogenetic defects in humans; however, the phenomenon of parsimony, whereby the same "morphogenetic" molecule, say, sonic hedgehog (SHH), is "deployed" simultaneously or sequentially during the morphogenesis (and even the histogenesis) of several/many embryonic primordia, makes it likely that a genetic/epigenetic disturbance of such an inductive system will have multiple effects on blastogenetic, organogenetic and perhaps also histogenetic events in the embryo. If causally defined, such a pattern of anomalies constitutes pleiotropy, and the embryo/fetus can be said to have a syndrome. If cause is unknown, the presumption of pleiotropy is less certain, and the fetus/infant may be said to have an "association" with low empiric recurrence risk.
Topics: Blastocyst; Congenital Abnormalities; Embryo, Mammalian; Embryonic and Fetal Development; Female; Humans
PubMed: 12503120
DOI: 10.1002/ajmg.10983 -
Surgical and Radiologic Anatomy : SRA Dec 2002Cyclotocephaly is a very rare malformative lethal condition which associates otocephaly (extreme hypoplasia of the mandibular arch with agnathia) and cyclopy with...
Cyclotocephaly is a very rare malformative lethal condition which associates otocephaly (extreme hypoplasia of the mandibular arch with agnathia) and cyclopy with proboscis. The head of a cyclotocephalic neonate from our Museum of Anatomy and Embryology was examined using computed tomography (CT). Cutaneous and osseous three-dimensional reformations were performed. Severe bony malformations were observed. A single orbital cavity was surrounded by a cartilaginous proboscis and a median fusion of maxillae, temporal and zygomatic bones. The single orbital cavity contained both paramedial eyeballs (synophthalmia). The external auditory meati and the ear pinnae were also parasagittal. No oral cavity and mandible were observed. Despite the poor conservation state of the brain, lobar holoprosencephaly was suspected. The mesencephalon and pituitary gland were absent. This exercise could lead to optimizing ultrasonographic prenatal diagnosis.
Topics: Abnormalities, Severe Teratoid; Head; Humans; Infant, Newborn; Male; Tomography, X-Ray Computed
PubMed: 12497224
DOI: 10.1007/s00276-002-0043-4 -
American Journal of Medical Genetics Oct 2002Three fetuses with agnathia-otocephaly complex representing different degrees of embryonic maldevelopment are reported. The study of the three cases and of the anterior...
Three fetuses with agnathia-otocephaly complex representing different degrees of embryonic maldevelopment are reported. The study of the three cases and of the anterior embryonic disc supports the concept that an altered embryologic development might have taken place at Carnegie stages 10 (embryonic days 22 or 23) and 11 (embryonic days 23-26). Karyotypic abnormalities and aberrant gene expression of sonic hedgehog and paired-related homeobox genes are discussed as the cytogenetic and molecular basis of agnathia-otocephaly complex.
Topics: Ear; Female; Genes, Homeobox; Hedgehog Proteins; Humans; Infant, Newborn; Male; Mandible; Trans-Activators
PubMed: 12244557
DOI: 10.1002/ajmg.10672 -
Development (Cambridge, England) Sep 2002Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is...
Mice heterozygous for the Otx2 mutation display a craniofacial malformation, known as otocephaly or agnathia-holoprosencephaly complex. The severity of the phenotype is dependent on the genetic background of a C57BL/6 (B6) strain; most of the offspring of Otx2 knock-out chimeras, which are equivalent to the F(1) of CBA and B6 strains, backcrossed with B6 females display reduction or loss of mandible, whereas those backcrossed with CBA females do not show noticeable phenotype at birth. The availability of phenotypically disparate strains renders identification of Otx2 modifier loci possible. In this study, a backcross of chimera with B6 was generated and genome-wide scans were conducted with polymorphic markers for non-mendelian distribution of alleles in Otx2 heterozygous mutant mice displaying abnormalities in the lower jaw. We identified one significant locus, Otmf18, between D18Mit68 and D18Mit120 on chromosomes 18, linked to the mandibular phenotype (LOD score 3.33). A similar replication experiment using a second backcross (N3) mouse demonstrated the presence of another significant locus, Otmf2 between D2Mit164 and D2Mit282 on chromosome 2, linked to the mandibular phenotype (LOD score 3.93). These two modifiers account for the distribution of the craniofacial malformations by the genetic effect between B6 and CBA strains. Moreover, Otmf2 contain a candidate gene for several diseases in mice and humans. These genetic studies involving an otocephalic mouse model appear to provide new insights into mechanistic pathways of craniofacial development. Furthermore, these experiments offer a powerful approach with respect to identification and characterization of candidate genes that may contribute to human agnathia-holoprosencephaly complex diseases.
Topics: Animals; Chromosome Mapping; Craniofacial Abnormalities; Crosses, Genetic; Ear; Embryonic and Fetal Development; Genetic Linkage; Genetic Markers; Genotype; Heterozygote; Homeodomain Proteins; Mandible; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Microsatellite Repeats; Nerve Tissue Proteins; Neural Crest; Otx Transcription Factors; Phenotype; Trans-Activators
PubMed: 12183386
DOI: 10.1242/dev.129.18.4347 -
Ultrasound in Obstetrics & Gynecology :... Jan 2002To investigate the prenatal appearance of the holoprosencephaly spectrum.
OBJECTIVE
To investigate the prenatal appearance of the holoprosencephaly spectrum.
METHODS
A database of 1750 fetuses with congenital anomalies identified by ultrasound was prospectively collected from 1987 to 2000. Among them, 30 cases (1.7%) with holoprosencephaly were prenatally identified and described.
RESULTS
The prevalence of holoprosencephaly in the Health Region of the National Center for Fetal Medicine in Norway was 1.26 : 10 000; the sex distribution (male : female) was 1.4 : 1. Holoprosencephaly was found in one dichorionic twin pregnancy and one pair of conjoined twins. Among the 30 cases of holoprosencephaly, 18 were alobar, five were semilobar, two were lobar, two were lobar variants, and three were anencephalic. The facial features varied considerably. Sixty-seven per cent (20/30) had associated structural anomalies that were not related to the cerebral and facial holoprosencephaly condition. Thirty-seven per cent (11/30) had detectable chromosome aberrations and 23% (7/30) had nonchromosomal syndromal origin. The size or shape of the head was abnormal in 83% (25/30) of holoprosencephaly cases.
CONCLUSION
This study indicates that holoprosencephaly represents a heterogeneous entity with different etiologies and clinical appearances. The fact that holoprosencephaly features are found associated with particular conditions such as fronto-nasal dysplasia (2/30; 6.7%), agnathia-otocephaly (3/30; 10%), and anencephaly (3/30; 10%), suggests that these may be underreported conditions in other large holoprosencephaly series.
Topics: Abnormalities, Multiple; Adolescent; Adult; Female; Holoprosencephaly; Humans; Hypertelorism; Karyotyping; Male; Norway; Pregnancy; Ultrasonography, Prenatal
PubMed: 11851965
DOI: 10.1046/j.0960-7692.2001.00154.x -
American Journal of Medical Genetics Jun 2001A genetic theory of "multifactorial" malformations, i.e., anomalies of blastogenesis or organogenesis, involving polygenic predisposition with morphogenetic threshold...
A genetic theory of "multifactorial" malformations, i.e., anomalies of blastogenesis or organogenesis, involving polygenic predisposition with morphogenetic threshold effect, was developed by Sewall Wright in the 1920s and remains an essential basis of birth defects biology. Because of the phenomenon of universality, i.e., the deployment of identical inductive, or pattern-forming, upstream molecular mechanisms during the earliest stages of mammalian morphogenesis, Wright's work on guinea pig otocephaly is highly pertinent to "corresponding," i.e., homologous malformations in humans. This concept is illustrated on the hand of a human fetus in the Vilnius (Lithuania) Pathological Museum with anotocephaly, i.e., anencephaly and otocephaly so severe as to correspond to Wright's guinea pig otocephaly grade 11 or 12. The observation also supports our apology for old museums and old books as repositories for anomalies, no less important for their rarity.
Topics: Anencephaly; Animals; Craniofacial Abnormalities; Fetal Diseases; Fetus; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Lithuania; Museums; Pathology
PubMed: 11391661
DOI: 10.1002/ajmg.1320 -
American Journal of Medical Genetics Feb 2000
Topics: Abnormalities, Multiple; Albuterol; Anti-Asthmatic Agents; Beclomethasone; Craniofacial Abnormalities; Ear, External; Female; Fetus; Humans; In Vitro Techniques; Infant, Newborn; Pregnancy; Theophylline; Ultrasonography, Prenatal
PubMed: 10706365
DOI: No ID Found