Search

We describe two de novo intrachromosomal duplications of 1p. One case is a dir ins dup(1)(q21p21p31) in a newborn girl with low birth weight, growth retardation, and tetralogy of Fallot. The other is a 10-month-old girl with developmental delay, craniosynostosis, plagiocephaly, and an inv dup 1p34.1p31. Although, these patients have manifestations in common with previous cases, they do not establish a syndrome. Interestingly, all males with duplications spanning 1p31 had genital anomalies, whereas females with duplications of the same region had normal genitalia. Thus, genes within 1p31 appear to control the development of male genitalia and tentatively exclude effects of tda1, a sex-determining gene in a region of mouse chromosome 4 syntenic to 1p36 in man. However, it is necessary to identify the human tda1 homologue and candidate genes within 1p31 before drawing final conclusions.

We report on a girl with a de novo monosomy Xpter-->Xp22.3 and trisomy 3pter-->3p23, normal development and stature, mildly affected phenotype, and learning disabilities with a low normal level of intelligence. Late replication studies using BudR demonstrated that the entire der(X) was inactive in 30% of cells. In 62% of cells the inactivation did not spread to the autosomal segment in the der(X). The normal X was inactivated in 8% of cells. Quantitative X-inactivation studies using the human androgen receptor locus assay (HAR) on peripheral leukocytes and buccal epithelial cells showed extreme skewing of methylation (90.4% of the paternal allele). The correlation of cytogenetic and molecular data suggest that the mild phenotype of the proposita is most likely due to preferential inactivation of the entire der(X), which seems to be of paternal origin.

We describe two de novo cases of extra r(8) confirmed by fluorescent in situ hybridization (FISH). Based on these two and eight additional cases of extra r(8) confirmed by FISH, the phenotype is better documented. One of our patients had minor facial anomalies, near-normal growth, and neurological development. She had a ring in each cell analyzed. The second had minor craniofacial anomalies and growth and mental retardation. He had a small or double-sized ring in each cell. The phenotype of these 10 cases ranges from almost normal in an adult with 10% mosaicism to variable degrees of minor anomalies, growth retardation, and mental retardation overlapping the mosaic +8 syndrome.

A heteromorphism of the short arm of 16 (16p+) was discovered in 2 unrelated infants. By G banding, the euchromatic variant appears as a light and a medium dark band just distal to the centromere. This results in an increase of the short arm by about 1/3. The same variant was present in the normal father and the normal paternal grandmother in one family and mildly retarded mother in the 2nd family. The anomalies of the 2 infants are not similar and are apparently unrelated to the 16p + variant. Though the discovery of such euchromatic variants is highly significant for clinical diagnosis, their genetic significance and mode of origin remain to be elucidated.

We describe clinical and chromosomal findings in two patients with del(4q). Patient 1, with interstitial deletion (4)(q21.1q25), had craniofacial and skeletal anomalies and died at 8 months of hydrocephalus. Patient 2, with interstitial deletion (4)(q25q27), had craniofacial and skeletal anomalies with congenital hypotonia and developmental delay. These patients shared certain manifestations with other del(4q) patients but did not have Rieger anomaly. Clinical variability among patients with interstitial deletions of 4q may be related to variable expression, variable deletion, or imprinting of genes within the 4q region.

We present three live-born infants with tetraploidy and compare them with two previously reported live-born infants with the same genetic defect. Common anomalies noted included microcephaly; a prominent, narrow forehead; microphthalmia/anophthalmia; cleft palate; orthopedic anomalies; genital ambiguity; and abnormalities of the central nervous system, including pituitary hypoplasia. Together these constitute a rather characteristic phenotype. An error in cytoplasmic cleavage is theorized to be a mechanism for the chromosome anomaly and is supported by the presence of parental polymorphisms in one of our cases; however, the presence of a small percentage of tetraploid cells in the leukocytes and skin fibroblasts of this patient's mother does not exclude maternal mosaicism as the basis for polyploidy in certain instances.

We describe a live-born male with 47,XY,+22. He had multiple congenital anomalies, severe growth retardation and psychomotor delay. Physical manifestations included broad nasal bridge, epicanthic folds, micrognathia, long philtrum, cleft palate, microcephaly with prominent occiput, apparently low-set malformed ears, heart murmur, genital anomaly, clinodactyly of the fifth fingers, and a low total finger ridge count. He died just before his 3rd birthday. Chromosome analysis by multiple banding techniques based on lymphocyte and fibroblast cultures confirm that the boy had complete trisomy 22.

Direct chromosome preparations of neonatal cord blood provides the unique opportunity for rapid chromosome analysis (turnaround time; 6 hr), without the necessity of bone marrow aspiration. Based on 42 samples we confirm the finding of Garnham and Sutherland [1987] for suitability of cord blood for direct chromosome preparation. Procedural modifications are provided for higher yield of cells for chromosome analysis. The procedure may well be of major significance for rapid diagnosis of neonates who suffer from aneusomy.