11/200. Coexistent holoprosencephaly and Chiari II malformation. Chiari II malformations and holoprosencephaly have been considered to be brain malformations that differ with respect to teratogenic insult, embryologic mechanism, and morphology. We herein describe coexistent Chiari II malformation and holoprosencephaly that occurred in a viable infant. A review of the literature regarding Chiari II malformations and holoprosencephaly suggests that a disturbance to the mesenchyme in early embryologic life may be the cause of both malformations. ( info) |
12/200. Cyclopia and exadactyly: CT and MRI findings. Cyclopia is a congenital abnormality consisting of fused orbits and a single eye and is the most extreme form of alobar holoprosencephaly. The present case describes the CT and MRI findings in the skull of a 33-week-old cadaver with alobar holoprosencephaly and exadactyly. ( info) |
13/200. On the association profound nerve deafness, semilobar holoprosencephaly, and minor midline developmental anomalies. A two-year-old boy with the combination of profound nerve deafness and semilobar holoprosencephaly associated with minor midline developmental anomalies is reported. In a review of the literature we could not find other examples of this possible syndromic association. ( info) |
14/200. holoprosencephaly, hypertelorism, and ectrodactyly in a boy with an apparently balanced de novo t(2;4) (q14.2;q35). A holoprosencephaly, hypertelorism, and ectrodactyly syndrome (HHES) was described in three previous cases in whom chromosomes were apparently normal. We report on a 3-year-old boy with HHES and a de novo apparently balanced t(2;4)(q14.2;q35) confirmed by fluorescent in situ hybridization. He had severe growth and mental retardation, lobar holoprosencephaly, hypertelorism, microphthalmos, and iris, choroid, and retina colobomata. Less-severe facial involvement correlates with the semilobar type of holoprosencephaly; limb defects consisted of foot ectrodactyly and syndactyly. All previous HHES cases were sporadic and of unknown cause. A cryptic imbalance secondary to the translocation (2;4) in our patient may explain the phenotype. ( info) |
15/200. Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele. A fetus with lobar holoprosencephaly and lumbosacral meningomyelocele associated with duplication of the short arm of chromosome 3 is reported. The anomalies were detected on fetal ultrasound at 20 weeks' gestation and the autopsy findings correlated well with the prenatal findings. The fetal karyotype was 46,XY,der(3)del(3)(p26) dup(3)(p26p21.3). The association of holoprosencephaly with duplication 3p is well known, but to the best of our knowledge this is the first reported association of meningomyelocele with 3p duplication. These findings suggest that a gene or genes with a crucial role in central nervous system development are located on the short arm of chromosome 3. ( info) |
16/200. Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly. We investigated the molecular basis of holoprosencephaly in a sporadic patient and identified a novel missense mutation in the signal sequence of the sonic hedgehog (Shh) gene. magnetic resonance imaging of the head showed a lobar type of holoprosencephaly and partial agenesis of the anterior corpus callosum. He was treated for craniosynostosis at 7 months of age. All three exons of the Shh gene were amplified by polymerase chain reaction from genomic dna of the patient and controls. Sequencing analysis of the polymerase chain reaction fragments, screened by single-strand conformation polymorphism analysis, revealed a heterozygous mutation of a T-to-C substitution at nucleotide position 50. This mutation predicted an amino acid replacement of leucine to proline at codon 17 located in the signal peptide of SHH protein. It probably disturbs the translocation of the protein into the endoplasmic reticulum and may lead to holoprosencephaly because of haploinsufficiency of Shh. ( info) |
17/200. Alobar holoprosencephaly at 9 weeks gestational age visualized by two- and three-dimensional ultrasound. We present the ultrasound detection of alobar holoprosencephaly (HPE) with cyclopia in an embryo of 9 weeks 2 days last menstrual period (LMP)-based gestational age; the crown-rump length (CRL) was 22 mm. The use of three-dimensional (3-D) ultrasound made additional diagnostic ultrasound tomograms possible, and the volume reconstructions improved the imaging and the understanding of the condition. ( info) |
| We describe a brother and sister who both had holoprosencephaly, polydactyly, cardiac lesions and a normal karyotype. The parents were first cousins and a diagnosis of pseudotrisomy 13 syndrome is suggested. This report provides further support that the inheritance of pseudotrisomy 13 syndrome is autosomal recessive. ( info) |
| We report an infant with holoprosencephaly (HPE), sacral anomalies, and situs ambiguus with a 46,XY,der(7)t(2;7)(p23.2;q36.1) karyotype as a result of an adjacent-1 segregation of a t(2;7)pat. The chromosomal abnormality was diagnosed prenatally after sonographic detection of HPE in the fetus. The baby was born at 37 weeks gestation, and died in the newborn period; he had dysmorphic features consistent with HPE sequence. Postmortem internal evaluation showed semilobar HPE, abdominal situs ambiguus, multiple segments of bowel atresia, dilatation of the ureters, and bony sacral anomalies. Molecular analysis confirmed hemizygosity for the SHH and HLXB9 genes, which are likely to be responsible for the HPE and sacral phenotypes, respectively. Immunohistochemical studies showed intact dopaminergic pathways in the mesencephalon, suggesting that midbrain dopamine neuron induction appears to require only one functioning SHH allele. ( info) |
20/200. Congenital nasal pyriform aperture stenosis associated with central diabetes insipidus. We describe a child who has central diabetes insipidus associated with congenital nasal pyriform aperture stenosis without any apparent anterior pituitary dysfunction. This association further strengthens the concept that congenital nasal pyriform aperture stenosis may be a microform of holoprosencephaly. ( info) |