phenylephrine-hydrochloride and Hernia--Umbilical

Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as omphalocele and anal stenosis. Autosomal recessive inheritance had been assumed because of consanguinity in the Oji-Cre population of Manitoba and reports of affected siblings, but no locus or cytogenetic aberration had previously been described.. This study shows that MOTA syndrome is caused by mutations in FREM1, a gene previously mutated in bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome. MOTA syndrome and BNAR syndrome can therefore be considered as part of a phenotypic spectrum that is similar to, but distinct from and less severe than, Fraser syndrome. Re-examination of Frem1(bat/bat) mutant mice found new evidence that Frem1 is involved in anal and craniofacial development, with anal prolapse, eyelid colobomas, telecanthus, a shortened snout and reduced philtral height present in the mutant mice, similar to the human phenotype in MOTA syndrome.. The milder phenotypes associated with FREM1 deficiency in humans (MOTA syndrome and BNAR syndrome) compared to that resulting from FRAS1 and FREM2 loss of function (Fraser syndrome) are also consistent with the less severe phenotypes resulting from Frem1 loss of function in mice. Together, Fraser, BNAR and MOTA syndromes constitute a clinically overlapping group of FRAS-FREM complex diseases.

Topics: Abnormalities, Multiple; Adolescent; Adult; Anal Canal; Animals; Anorectal Malformations; Anus, Imperforate; Base Sequence; Child; Child, Preschool; Coloboma; Extracellular Matrix Proteins; Eyelids; Female; Fraser Syndrome; Gene Dosage; Hernia, Umbilical; Humans; Hypertelorism; Male; Mice; Molecular Sequence Data; Mutation; Nose; Nose Diseases; Oligonucleotide Array Sequence Analysis; Pedigree; Phenotype; Receptors, Interleukin; Reverse Transcriptase Polymerase Chain Reaction; Syndrome

Major characteristics of the acrocallosal syndrome include severe mental retardation, agenesis or hypoplasia of the corpus callosum, and polydactyly of fingers and toes. In the past few years, anencephaly has also been noted, together with other midline defects. We report on a nonconsanguineous, Norwegian couple with a history of two pregnancies with a male and a female fetus, respectively, with anencephaly, median cleft lip and palate, omphalocele, and preaxial polydactyly, suggesting the diagnosis of the acrocallosal syndrome. Both fetuses also lacked eyes and nose, a finding not previously reported in the acrocallosal syndrome. Microphthalmia has been reported in the hydrolethalus syndrome, which may be caused by mutations in the same gene as the acrocallosal syndrome. The present report adds support to the hypothesis that the acrocallosal and hydrolethalus syndromes may be allelic conditions. The family history is consistent with autosomal recessive inheritance.

Topics: Abnormalities, Multiple; Agenesis of Corpus Callosum; Anencephaly; Anophthalmos; Cleft Lip; Cleft Palate; Corpus Callosum; Female; Fetus; Genes, Recessive; Hernia, Umbilical; Humans; Male; Nose; Nuclear Family; Polydactyly; Pregnancy; Syndrome; Ultrasonography, Prenatal

Topics: Abdominal Muscles; Anus, Imperforate; Cleft Lip; Cleft Palate; Congenital Abnormalities; Disorders of Sex Development; Genetic Counseling; Heart Defects, Congenital; Hernia, Umbilical; Hernias, Diaphragmatic, Congenital; Humans; Infant Care; Infant, Newborn; Intestinal Atresia; Neural Tube Defects; Nose; Tracheoesophageal Fistula; Transportation of Patients

Topics: Abnormalities, Multiple; Cleft Lip; Craniofacial Dysostosis; Encephalocele; Female; Fingers; Foot Deformities, Congenital; Genetic Counseling; Hernia, Umbilical; Humans; Infant, Newborn; Nose; Radiography; Skull; Syndrome

Topics: Abnormalities, Multiple; Cleft Palate; Congenital Abnormalities; Deafness; Esophageal Stenosis; Female; Glaucoma; Hernia, Umbilical; Hernias, Diaphragmatic, Congenital; Hip Dislocation, Congenital; Humans; Hydronephrosis; Hymen; Infant, Newborn; Intestinal Atresia; Jaw Abnormalities; Lip; Nose; Tongue

Topics: Abnormalities, Multiple; Child; Consanguinity; Cryptorchidism; Eye Abnormalities; Eye Enucleation; Eyelids; Hernia, Umbilical; Humans; Hydrophthalmos; Male; Microphthalmos; Nose; Penis