Noreen L. Rudd

A dominantly inherited cytogenetic anomaly: A possible cell division mutant

SummaryShort-term lymphocyte cultures from three unrelated patients showed an increased frequency of mitoses with separated centromeres and splayed chromatids in the presence of colcemid. We refer to this phenomenon as premature centromere division (PCD). In two of the three patients the frequency of PCD in lymphocytes decreased when colcemid was omitted prior to harvest but was still higher than controls, whereas in the third patient, the frequency appeared unchanged. Cultured fibroblasts from the latter patient exhibited increased tetraploidy and multinucleated cells. Transmission of the trait in the three families was compatible with autosomal dominant inheritance. Time lapse cinemicrographic studies on fibroblasts from one patient demonstrate a shortened metaphase time, suggesting that the separation of chromatids observed in this patient may indeed be premature. The nature of the mutation(s) and phenotypic correlation if any is unknown.

Prenatal diagnosis of hypophosphatasia.

Hypophosphatasia is a rare, recessively inherited metabolic disorder characterized by low serum and tissue alkaline phosphatase, the presence of phosphoethanolamine in the urine1 , 2 and osseous ch...

Two pairs of male monozygotic twins discordant for Wiedemann-Beckwith syndrome

Wiedemann-Beckwith syndrome (WBS) is a congenital anomaly syndrome which classically consists of exomphalos, macroglossia, and gigantism. The syndrome is also associated with a variety of minor anomalies and affected individuals have an increased risk of developing rare embryonal cell tumors. To date, 15 monozygotic (MZ) twin pairs have been reported of which 13 are discordant for WBS. All except one pair of the discordant WBS twin pairs have been female. We report two pairs of male MZ twins, each discordant for WBS.

The genetics of and associated clinical findings in humero‐radial synostosis

This paper compares the manifestations of sporadic, dominantly inherited and recessively inherited humero‐radial synostosis with the aim of determining ways of separating these forms on clinical grounds. The genetic forms are characterized by bilateral involvement and by lack of the distal ulnar malformations and the absence of digits that are common in the sporadic cases. The majority of patients with the dominantly inherited form have a characteristic pattern of anomalies, including brachymesophalangy, and the recessive cases have a high frequency of malformations in addition to those of the limbs. Consanguinity is frequent in the families of recessive cases. Four additional patients are presented; two of them illustrate many of the features of the phocomelic syndrome reported by Herrmann et al. (1969). A possible teratogenic cause of these cases is discussed.

Congenital tracheal stenosis in Pfeiffer syndrome

We report an infant with Pfeiffer syndrome (acrocephalosyndactyly type V) and a solid cartilaginous trachea lacking rings. This airway abnormality has been reported in a child with Crouzon syndrome but has not been described in Pfeiffer syndrome.

Somatic recombination rather than uniparental disomy suggested as another mechanism by which genetic imprinting may play a role in the etiology of Prader-Willi syndrome

SummarySix Prader-Willi syndrome (PWS) patients with normal karyotypes and their parents were analyzed to determine the nature of the molecular aberrations present in the proximal region of 15q and to determine the parental origin of the aberrant chromosome 15. In addition, the likehood that uniparental disomy plays a significant role in the etiology of PWS patients with normal karyotypes was studied. Restriction fragment length polymorphisms (RFLPs) recognized by seven probes [pML34 (D15S9), pTD3-21, pCGS0.9, pCGS1.1 (D15S10), IR4.3 (D15S11), IR10.1 (DS15S12), p189-1 (D15S13), IR39 (D15S18), and CMW-1 (D15S24)] mapping to the Prader-Willi chromosome region (PWCR) and an additional two probes [pMS1-14 (D15S1); the cDNA of neuromedin B] mapping elsewhere on chromosome 15 were analyzed in the six PWS patients and their parents. Copy number of each locus within the PWCR was determined by densitometry. Molecular rearrangements of the proximal region of 15q were observed in all of the six probands and the origin of the aberrant chromosome 15 when determined was consistently paternal in origin. While data obtained from our six patients does not support the mechanism of disomy, results obtained from three of the six patients show more complex rearrangements hypothesized to have resulted from somatic recombination. These rearrangements have resulted in acquired homozygosity and the lack of a paternal allele at various loci within the PWCR. The presence of only a maternal contribution at certain loci as the result of somatic recombination may be another mechanism by which genetic imprinting plays a role in the presentation of the PWS phenotype.

Infant outcome following mid-trimester amniocentesis: development and physical status at age six months.

Summary. Ninety‐one infants whose mothers had had amniocentesis, because age increased their risk for a fetal chromosome abnormality, were compared with 53 infants whose mothers chose not to have the test. Mental and motor development and temperament were studied to assess potential influence of amniocentesis on the brain. Physical growth was assessed and the infants were examined for orthopaedic abnormalities and needle injury. The results indicated that amniocentesis does not appear to influence infant mental and motor development, temperament, physical growth or the risk of orthopaedic abnormalities. However, amniocentesis is not entirely free of risk because several of the infants had needle marks. Reassessment of the cohort at age 4 and 7 years and will provide information on the potential longer term consequences of mid‐trimester amniocentesis.

Familial caudal dysgenesis: evidence for a major dominant gene

Four sibs with varying degrees of caudal dysgenesis are described. Case 1 showed aberrant umbilical cord vasculature with a single umbilical artery near the placental insertion. Cases 2 and 3 showed full sirenomelia, one with a complex congenital heart defect. Case 4 had an imperforate anus and an excessively long umbilical cord. The fathers half‐sib had an imperforate anus, rectovaginal fistula and genitourinary anomalies. A dominant gene with reduced penetrance is likely.

Midtrimester amniocentesis: Obstetric outcome and neonatal neurobehavioral status

The possible effects of midtrimester genetic amniocentesis on neurobehavioral status were studied in newborn infants of women who had had the procedure (N = 100) and in newborn infants of women who had declined the test (N = 56). Brazeltons Neonatal Behavioral Assessment Scale was administered to newborn infants born at term and did not reveal consequences of amniocentesis on neonatal orientation, range of state, motor ability, autonomic regulation, regulation of state, response decrement, or reflexes. Information on obstetric complications also was obtained. The findings raised questions regarding the temporal relationship between amniocentesis and fetal loss and focused attention on preterm birth as a potential risk that warrants further investigation. This study provides the foundation for our prospective longitudinal follow-up in which the cohort will be reassessed later in infancy and in childhood.