Joseph W. Towner

Genetic and clinical studies in 13 patients with the Wolf-Hirschhorn syndrome [del(4p)]

SummaryClinical and cytogenetic studies are reported on 13 patients with Wolf-Hirschhorn syndrome. The oldest of the living twelve probands is 24 years of age. Three of these patients has a translocation involving the short arm of chromosome 4, and in one of these the anomalous chromosome was inherited from the father. Another three patients were believed, on the basis of GTG-staining, to have a translocation although the origin of the translocated chromatin could not be identified. In the remaining seven patients the anomalous chromosome appeared to be a simple deletion, although in two cases a translocation could not be reled out. Cytogenetic studies in these patients suggest that the critical deletion involved in Wolf-Hirschhorn syndrome is within 4p 16.

Chromosomal anomalies in patients with retinoblastoma

Karyotypes from 50 persons with retinoblastoma confirmed by histopathological examination were studied by conventional staining and Giemsa‐banding techniques. Two chromosomal anomalies were found. An interstitial deletion of the long arm of No. 13 chromosome was identified by Giemsa‐banding in the karyotypes from a boy with unilateral retinoblastoma. Another boy with unilateral tumor had a karyotype of 47, XXY. These findings provide additional evidence that a deletion of chromosome No. 13, most likely involving band 13q14, is associated with the development of retinoblastoma. In conjunction with other reports, our findings also suggest that retinoblastoma may be found more frequently in children with chromosomal aneuploidy.

Inherited partial duplication of chromosome No. 15

A boy with unusual facial appearance and mental retardation was found to have duplication for the distal half of the long arm of chromosome No. 15 and possibly deficiency for the distal end of the long arm of No. 21. The chromosome abnormality was inherited from his mother, who had a translocation involving chromosomes Nos. 15 and 21. Giemsa-banding localized the break point in chromosome No. 15 just distal to the intense band at the midportion of the long arm. The break point in chromosome No. 21 appeared to be at the distal end of the long arm. The difficulty encountered in cytogenetic analysis of the propositus with conventional staining, the importance of chromosome analysis of the parents, and the application of differential staining techniques are also presented.

Trisomy 13 in Two Infants with Cyclops

Two infants with cyclops malformation were born at the University of Southern California Medical Center during the past three years. The karyotypes of both infants demonstrated an extra chromosome No. 13: one with 47,XX,+13 and one with 46,XX,-14,+t(13q14q). The physical findings, karyotypes with trypsin-Giemsa banding, and association of trisomy 13 syndrome with cyclops malformation are presented.

Acid α-glucosidase in amniotic fluid

Abstract Amniotic fluid contains α-glucosidase activity. This enzyme has a pH optimum of 5.8 and is distinguishable from the lysosomal α-glucosidase associated with Pompes disease which has a pH optimum of 4.1. In addition to the pH optimum, the two enzymes differ in response to KCl, turanose and heat treatment. α-Glucosidase activity in amniotic fluid cannot be used for the prenatal diagnosis of Pompes disease.

Additional manifestations of the Neu-Laxova syndrome.

A newborn female with intrauterine growth retardation, bilateral cleft lip and palate, absent external nares and eyelids, low set ears, short contracted limbs, webbed digits, intestinal malrotation, and unilateral renal agenesis is reported. These multiple malformations are considered part of the Neu-Laxova syndrome.

A Fetus With Recombinant of Chromosome 8 Inherited From her Carrier Father

SummaryA pericentric inversion of chromosome 8, inv(8)(p23q22), in a male carrier resulted in an unbalanced recombinant, rec(8)dup q, inv(8)(p23q22), which was diagnosed prenatally. The features seen in the aborted fetus resembled the features seen in a previously affected child who received the identical recombinant from her carrier mother. In this particular inversion involving chromosome 8, both male and female carriers risk producing an unbalanced progeny. Different familial pericentric inversions are reviewed for the presence or absence of unbalanced recombinants.

Duplication of the segment q12.2→qter of chromosome 22 due to paternal inversion 22(p13q12.2)

SummaryA 1730-g male infant, born at 37 weeks gestation, had multiple congenital anomalies, consisting of microcephaly, hypertelorism, bilateral cleft lip and palate, micrognathia, lowset ears, and cryptorchidism. Chromosome analysis showed a recombinant 22 derived from the paternal inversion (22) (p13q12.2). The probands karyotype is 46,XY,rec(22),dup q,inv(22)(p13q12.2)pat, which has a duplication of q12.2→qter. An identical recombinant has been reported in a female infant in Mexico whose mother was a carrier of the inversion. Similar congenital anomalies present in these two patients demonstrate the phenotype of duplication of the distal long arm 22. This report also documents the occurrence of an identical inversion in two apparently unrelated Mexican families.

Prenatal Diagnosis of an Inherited Translocation Between Chromosomes No. 9 and 18

A phenotypically normal woman has an apparently balanced reciprocal translocation between chromosomes No. 9 and No. 18 (translocation 9p-; 18p+), which was transmitted in an unbalanced state to an infant and a fetus. In the latter instance, chromosome analysis of cultured amniotic cells disclosed an abnormal karyotype, which was identical to that of the first affected child. The therapeutically aborted fetus was grossly abnormal and resembled the affected child. The physical features noted are those frequently associated with chromosome abnormalities, although not diagnostic for any specific syndrome. We presume that the chromosome abnormality in the affected offspring represents partial duplication of the short arm of chromosome No. 9 and partial deletion of the short arm of chromosome No. 18. No marked resemblance is noted between these cases and reported cases of trisomy 9 or of partial deletion of the short arm of 18.

Familial inversion of chromosome No. 8

SummaryAn infant with multiple congenital anomalies was found to have a duplication-deficiency disorder involving chromosome No. 8. The abnormality was identified as an unbalanced recombinant inherited from the mother who was a carrier of a pericentric inversion of chromosome No. 8. The inversion was observed in several members of this family, including a fetus who was diagnosed by an amniocentesis. The inverted chromosome was demonstrated only with the use of a differential staining technique, in this case, by trypsin-Giemsa banding.