Monochorionic diamniotic twins concordant for anencephaly: a case report.

BACKGROUND: Anencephaly occurs in 1.4-4.7 per 10,000 deliveries and is thought to result from failed closure of the anterior neuropore at 24-26 days post fertilization. Among twins, risk for congenital malformations is greatest among monozygotic twins. Several occurrences of twin pairs being discordant for neural tube defects have been reported: 1 twin affected with anencephaly and co-twin affected with holoprosencephaly, spina bifida or encephalocele, is consistent with a multifactorial pattern of inheritance. We present an instance of monochorionic diamniotic twins concordant for anencephaly. CASE: An 18-year-old, gravida 1, para 0, Caucasian woman presented with monochorionic diamniotic twin gestation at 22 weeks. Prenatal ultrasound identified polyhydramnios, anencephaly, ventricular septal defect and suspected rocker-bottom feet in twin A. Twin B was identified as anencephalic, with left renal agenesis and spinal distortion visualized on ultrasound. Postnatal cytogenetic evaluations of placenta, umbilical cord blood and fetal skin samples from both twins revealed 46,XX karyotypes. CONCLUSION: A rare case of a monochorionic diamniotic gestation concordant for anencephaly is presented. Previously published reports of concordant twin anencephaly have postulated a possible autosomal recessive or multifactorial mode of inheritance. Subsequent pregnancies with anencephaly or other open neural tube defects would indicate a mendelian process.

Prenatal identification of a novel R937P L1CAM missense mutation.

The L1 cell adhesion molecule (L1CAM) is a protein encoded by a gene that has been localized to Xq28, is a member of the immunoglobulin superfamily of neuronal cell adhesion molecules, and plays a role in CNS development and maturation. L1CAM is expressed in neurons and Schwann cells, where it is active in neurite overgrowth, adhesion fasciculation, migration, myelination, and axon guidance. Mutations within the gene have been associated with phenotypic changes that include hydrocephalus due to aqueductal stenosis, agenesis or hypoplasia of the corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia, and adducted thumbs. Here, we present a 19-year-old primigravida Caucasian woman who was referred to us in the 27th week of the pregnancy because of fetal polyhydramnios and ventriculomegaly. Our evaluation identified a male fetus with hydrocephalus, ventriculomegaly, aqueductal stenosis, and polyhydramnios. An amniocentesis was performed, and isolated fetal DNA revealed a hemizygous G > C mutation in codon 2809 of exon 21 of the L1CAM gene. The patient was later tested and identified to be a carrier of the same mutation. The fetus was delivered during the 38th week. Neonatal physical examination revealed marked frontal bossing, contractures of the feet with rocker bottom appearance, and hyperactive reflexes with ankle and knee clonus. He died at 4 months of life.

Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta.

Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.