Clinical analysis of a large kindred with the Pallister ulnar-mammary syndrome

Abstract

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.

Mammary gland, limb and yolk sac defects in mice lackingTbx3,the gene mutated in human ulnar mammary syndrome

“…the forelimb and apocrine glands, but also including abnormal external genitalia such as imperforate hymen, micropenis and imperforate anus, is seen in heterozygous individuals (Bamshad et al, 1999;Bamshad et al, 1996). Second, in human heterozygotes, the forelimb is more frequently and more severely affected than the hindlimb, whereas in homozygous mutant mice, the hindlimb is always the more severely affected limb.…”

“…As the name suggests, the syndrome is predominately characterized by posterior forelimb deficiencies or duplications, involving the ulna and little finger (with rare involvement of the hindlimb), and apocrine/mammary gland hypoplasia or dysfunction with absent or abnormal nipples. Other common features are abnormal dentition, delayed puberty, genital abnormalities and growth retardation (Bamshad et al, 1995;Bamshad et al, 1999;Bamshad et al, 1996). There have been no reports of humans homozygous for TBX3 mutations.…”

TBX3 and Its Isoform TBX3+2a Are Functionally Distinctive in Inhibition of Senescence and Are Overexpressed in a Subset of Breast Cancer Cell Lines

“…Mammary gland abnormality ranges from hypoplasia to absence of breasts in males and females (11). The disease gene was identified as TBX3 by linkage analysis (9,10).…”

TBX3 (T-box 3)

“…Disease Characterised by posterior limb abnormalities, such as malformed ulna and posterior digits, hypoplasia and/or dysfunction of the mammary and apocrine glands, absent axillary hair, abnormal dentition, delayed puberty in males and genital anomalies (Bamshad et al, 1996;Bamshad et al, 1997).…”