New recessive syndrome characterized by increased chromosomal breakage and several findings which overlap with Fanconi anemia.

We describe four cases with several findings of Fanconi anemia (FA), but without hypersensitivity to DNA cross-linking that is the distinguishing characteristic of FA. Two of the cases are male and female sibs of Hispanic origin, age 6 years and 11 months, respectively. Both have short stature, failure to thrive, absent thumbs, short palpebral fissures, and skin pigmentation abnormalities. The girl also has developmental "dysplasia" of her hips. Presently, both siblings are hematologically normal. Elevated baseline chromosome breakage was observed in the boy, but not in the girl. Neither sib showed elevated diepoxybutane (DEB)-induced chromosomal breakage. In a subsequent pregnancy, prenatal studies showed slightly elevated baseline and DEB induced chromosome breakage (greater than normal, but lower than the established range for FA). The fetus had intrauterine growth retardation and an absent right thumb. A review of cases referred to the International Fanconi Anemia Registry for DEB testing showed one additional case with similar findings. That patient, a girl, of Caucasian English ancestry, age 14 years, had short stature, a history of failure to thrive, skin pigmentation abnormalities, absent right thumb, hypoplastic left thumb, and hydrocephalus that resolved spontaneously. Elevated baseline chromosome breakage was observed in skin fibroblasts but not in lymphocytes. We postulate that these cases represent a previously undescribed autosomal recessive syndrome. These and other previously reported cases provide evidence for alternative genetic mechanisms that may result in developmental anomalies similar to those seen in FA.

Fragile X syndrome in two siblings with major congenital malformations.

We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2 1/2, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46, XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed.

Families created through ovum donation: a preliminary investigation of obstetrical outcome and psychosocial adjustment.

PURPOSE: This study attempted to obtain preliminary follow-up information regarding obstetrical outcomes and the psychosocial well-being of families created through the ovum donation. There is presently very little known about this population with respect to obstetrical care, health status of offspring, family and marital relationships of recipient couples, or how couples feel about having chosen ovum donation as a family-building option. RESULTS: Fifty-nine couples were initially surveyed and, ultimately, extensive information was obtained for 30 husbands, 31 wives, and 51 offspring. There was a very high percentage of cesarean section deliveries (81.6%), and although a few children experienced health problems at birth, they are all now in good health and developmental milestones are within normal limits. Information was also obtained about breast-feeding experiences, choice of donor (known [sister] or anonymous), reasons for choosing ovum donation over other parenting options, and the impact of this choice on marital and family relationships. Demographic data were also obtained. CONCLUSIONS: For many infertile couples, the long struggle to become parents culminated in a successful birth, and the experience of pregnancy seemed to meet a need to be both biological and psychosocial parents. In general, subjects were extremely cooperative with the investigation and they indicated a desire to learn as much as possible about the psychosocial status of families created through ovum donation. As the assisted reproductive technologies move rapidly into the 21st century, it now seems imperative that health and mental health professionals gain more knowledge about the impact of third party reproduction and the psychosocial adjustment and well-being of families created by this medical technology.

Rapid exclusion of chromosomal aneuploidies by fluorescence in situ hybridization prior to fetal surgery for obstructive uropathy--a case report.

Ultrasound of a fetus at 17 weeks gestation revealed posterior urethral valve syndrome with anhydramnios. Fluorescence in situ hybridization (FISH) to detect aneuploidies of chromosomes 13, 18, 21, X and Y was performed on transitional cells from the fetal bladder obtained at percutaneous vesicocentesis, followed by conventional cytogenetics. Fetal urine was chosen due to unavailability of amniotic fluid for karyotypic analysis. A nonlethal (disomic) karyotype was suggested by FISH, and thus placement of a vesicoamniotic shunt was performed. The ability to prognosticate in cases of obstructive uropathy is not absolute, and fetal surgery for relief of urinary obstruction is best performed at the earliest possible gestational age. Thus, all available means for rapidly ruling out lethal congenital anomalies should be undertaken in cases of obstructive uropathy prior to any decision regarding fetal surgery.