Ulnar-mammary syndrome (UMS) is a pleiotropic disorder affecting limb, apocrine-gland, tooth, hair, and genital development. Mutations that disrupt the DNA-binding domain of the T-box gene, TBX3, have been demonstrated to cause UMS. However, the 3' terminus of the open reading frame (ORF) of TBX3 was not identified, and mutations were detected in only two families with UMS. Furthermore, no substantial homology outside the T-box was found among TBX3 and its orthologues. The subsequent cloning of new TBX3 cDNAs allowed us to complete the characterization of TBX3 and to identify alternatively transcribed TBX3 transcripts, including one that interrupts the T-box. The complete ORF of TBX3 is predicted to encode a 723-residue protein, of which 255 amino acids are encoded by newly identified exons. Comparison of other T-box genes to TBX3 indicates regions of substantial homology outside the DNA-binding domain. Novel mutations have been found in all of eight newly reported families with UMS, including five mutations downstream of the region encoding the T-box. This suggests that a domain(s) outside the T-box is highly conserved and important for the function of TBX3. We found no obvious phenotypic differences between those who have missense mutations and those who have deletions or frameshifts.

Prenatal diagnosis of trisomy 18 by amniocentesis in the latter half of pregnancy is now a common event. Accurate prognostic information is crucial for families making decisions about delivery management. Three recently published studies showed much shorter survival for trisomy 18 than was reported by earlier papers. For this reason, we studied trisomy 18 survival. We examined chromosome laboratory records to find all trisomy 18 diagnoses made in Utah between 1979 and 1988. Death certificates and hospital records were used to determine survival. We found 64 liveborn cases with trisomy 18 out of 388,563 total births over the 10-year period, a prevalence of 1/6071. Our results show a median survival of 4 days and a 1 week survival of 45%, similar to that reported in the 3 recent studies. However, we had a significantly greater survival at 6 months (9% in Utah versus 3% in Denmark) and 1 year (5% versus 0 in the 3 studies). In contrast to recent studies, earlier investigations showed 80% survival at 2 weeks and 8% at 1 year. It is not surprising that recent studies show shorter survival, since in the 1960s the diagnosis was typically not made until age 2 months. With prenatal and neonatal diagnosis many cases which would have died prior to detection in earlier times are now diagnosed. The longer survival discrepancies are more difficult to explain, but may simply be due to small numbers.

Ring chromosome 17 is a rare cytogenetic abnormality, with 12 previous reports in the literature. Some have a relatively mild phenotype characterized by seizures, mental retardation, skin changes and short stature. Other patients have Miller-Dieker syndrome (MDS), which includes lissencephaly, multiple dysmorphic features, severe mental retardation and shortened life expectancy. We describe two new cases of ring chromosome 17 and review the literature. Our cases and the other reports of patients without a deletion encompassing the Miller-Dieker region, delineate a fairly distinctive subgroup of individuals with ring 17, whose phenotype consists of growth and mental retardation, seizures, minor dysmorphic features, café-au-lait spots and retinal flecks. This classification of ring 17 into two distinct groups based on the size of the deletion and the phenotypic manifestations should facilitate clinical suspicion of this rare chromosomal abnormality.

The ulnar‐mammary syndrome (UMS) is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty in males, and genital anomalies. We present the clinical descriptions of 33 members of a six generation kindred with UMS. The number of affected individuals in this family is more than the sum of all previously reported cases of UMS. The clinical expression of UMS is highly variable. While most patients have limb deficiencies, the range of abnormalities extends from hypoplasia of the terminal phalanx of the 5th digit to complete absence of the ulna and 3rd, 4th, and 5th digits. Moreover, affected individuals may have posterior digital duplications with or without contralateral limb deficiencies. Apocrine gland abnormalities range from diminished axillary perspiration with normal breast development and lactation, to complete absence of the breasts and no axillary perspiration. Dental abnormalities include misplaced or absent teeth. Affected males consistently undergo delayed puberty, and both sexes have diminished to absent axillary hair. Imperforate hymen were seen in some affected women. A gene for UMS was mapped to chromosome area 12q23–q24.1. A mutation in the gene causing UMS can interfere with limb patterning in the proximal/distal, anterior/posterior, and dorsal/ventral axes. This mutation disturbs development of the posterior elements of forearm, wrist, and hand while growth and development of the anterior elements remain normal. © 1996 Wiley‐Liss, Inc.

Ulnar-mammary syndrome (UMS) is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty and genital anomalies. We report the mapping of a gene causing UMS to chromosome 12q23-24.1. Linkage analysis generated a positive lod score of 6.21 at theta = 0.00 with the marker D12S79, and recombinants bracket the UMS gene to a 21 cM region. This region contains a locus for Holt-Oram syndrome (HOS) suggesting that the genes for UMS and HOS may be allelic or closely linked. The identification of the gene causing UMS will be an important step toward understanding the molecular mechanisms that control limb and apocrine gland development.