1/3. Alobar holoprosencephaly: report of two cases with unusual findings.holoprosencephaly, a disorder resulting from failure of cleavage or incomplete differentiation of the forebrain structures at various levels or to various degrees, is related to hereditary factors, chromosomal anomalies, cytogenetic abnormalities, and environmental teratogenic factors. We report on 2 cases of alobar holoprosencephaly, with similar physical findings, including microcephaly, microphthalmia, cebocephalus, choanal atresia, pseudo cleft palate, distended abdomen, and acrocyanosis. The brain echogram of these 2 patients demonstrated fused thalami and a single large U-shaped ventricular cavity. Chromosome studies of these 2 patients were normal. The findings of the autopsies confirmed the clinical presentations. One of our cases had a clinical picture similar to that of holoprosencephaly-polydactyly syndrome. The other had the rare anatomical finding of a polylobuated spleen. Because of the poor prognosis of alobar holoprosencephaly, early prenatal diagnosis is recommended.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/3. Prenatal sonographic diagnosis of truncus arteriosus associated with holoprosencephaly.We present the case of a truncus arteriosus associated with holoprosencephaly detected in a fetus in the first trimester and the sonographic findings that established this diagnosis. A physical exam was performed on a 35-year-old pregnant woman, gravida 2, para 1. At 20 weeks, sonography showed large-for-date uterine size. Fetal biometry was consistent with menstrual age. amniotic fluid volume was elevated to 25 AFI cm. Fetal echocardiography revealed a single common artery arising from the heart, a ventricular septal defect, and other cardiac defects. Abnormalities of the fetal brain and face were also shown via sonography, including the presence of a common lateral ventricle without falx cerebri. Alobar holoprosencephaly, the most severe form of holoprosencephaly, was diagnosed. Prenatal chromosomal analysis was offered and the patient elected to have cordocentesis. The chromosome study was normal. Success in surgical repair of truncus arteriosus is established, but alobar holoprosencephaly is associated with neonatal death. Continuation of the pregnancy carried risks for the mother. After proper counseling, the parents of this fetus were offered and accepted termination of pregnancy. A male abortus weighing 320 grams was delivered. Postnatal findings and autopsy confirmed the diagnosis.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/3. Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly.holoprosencephaly (HPE) is a genetically and phenotypically heterogenous disorder involving the development of forebrain and midface, with an incidence of 1:16,000 live born and 1:250 induced abortions. This disorder is associated with several distinct facies and phenotypic variability: in the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. The less severe form features facial dysmorphia characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum. Several intermediate phenotypes involving both the brain and face have been described. One of the gene loci, HPE3, maps to the terminal band of chromosome 7. We have performed extensive physical mapping studies and established a critical interval for HPE3, and subsequently identified the sonic hedgehog (SHH) gene as the prime candidate for the disorder. SHH lies within 15-250 kilobases (kb) of chromosomal rearrangements associated with HPE, suggesting that a 'position effect' has an important role in the aetiology of HPE. As detailed in the accompanying report, this role for SHH is confirmed by the detection of point mutations in hereditary HPE patients.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |