Breasts And/or Nipples, Aplasia Or Hypoplasia Of, 2

A number sign (#) is used with this entry because of evidence that aplasia or hypoplasia of the breasts and/or nipples-2 (BNAH2) is caused by homozygous mutation in the PTPRF gene (179590) on chromosome 1p34. One such family has been reported.

Description

Congnital aplastic deformities of the breast include amastia (total absence of breasts and nipple), athelia (absence of the nipple), and amazia (absence of the mammary gland). Most common is amastia. Bilateral absence of the breasts may occur as an isolated anomaly or may be associated with a syndrome or a cluster of other anomalies, including anhidrotic ectodermal dysplasia (305100) or Poland syndrome (173800) (summary by Papadimitriou et al., 2009).

For a discussion of genetic heterogeneity of aplasia or hypoplasia of the breasts and/or nipples, see 113700.

Clinical Features

Kowlessar and Orti (1968) described a sister and brother, born of first-cousin parents, who had bilateral absence of breasts and nipples. Examination of the girl at 2.75 years of age was normal except for absence of any breast structures by inspection or palpation. External genitalia were normal and normal infantile uterus was present. Her brother was noted at birth to have absence of the breasts and nipples. Karyotype and dermatoglyphic patterns were normal.

Borck et al. (2014) reported 2 sibs and their cousin, from a consanguineous family of Israeli Arab origin, who had unilateral or bilateral absence of breast tissue and/or nipples. The sister was examined at 2.75 years of age and noted to have absence of the left areola and nipple; ultrasound examination showed no breast bud or nipple on the left side, whereas the right breast bud and nipple were of normal size and morphology. The pectoralis muscles were present and normally developed, and she had no limb malformations. Her 20-month-old brother had hypoplasia and inversion of the left nipple. Both sibs exhibited minor facial dysmorphisms, including arched eyebrows with an inverted V-shape laterally, small earlobes, flat philtrum, broad nasal tip, and mildly anteverted nares. Genital examination was normal in both, and motor and cognitive development were normal. Their first-cousin parents had normal eyebrows and normal breasts and nipples. A 13-year-old male first cousin to the sibs, who was also born of consanguineous parents, had bilateral absence of the nipples and an eyebrow shape similar to that of the sibs as well as slightly pointed upper ear helices and bilateral single transverse palmar creases. He had undergone orchidopexy for bilateral undescended testes and meatotomy for urethral stenosis. Pubertal development occurred normally and endocrine evaluation was normal. Kidneys were of normal size and structure by ultrasound; nails and sweating were normal, although he had small mandibular incisors and widely spaced teeth. None of the patients had anomalies of glucose metabolism or obesity.

Mapping

In a consanguineous pedigree of Israeli Arab origin with unilateral or bilateral absence of breast tissue and/or nipples, Borck et al. (2014) performed genomewide linkage analysis and obtained a maximum lod score of 3.31 at chromosome 1p34.2-p32.3, which was the only region in the genome with a lod score greater than 3. SNP analysis and haplotype reconstruction defined a 15.89-Mb critical region, flanked by SNPs rs633297 and rs17115767.

Molecular Genetics

In a consanguineous pedigree of Israeli Arab origin with unilateral or bilateral absence of breast tissue and/or nipples mapping to chromosome 1p34, Borck et al. (2014) sequenced 3 candidate genes and identified homozygosity for a 2-bp deletion in the PTPRF gene (179590.0001) that segregated with disease in the family and was not found in the dbSNP (build 137) database or in approximately 6,400 European and African American individuals sequenced at this position in the NHLBI Exome Sequencing Project database. Analysis of PTPRF in 2 additional unrelated patients with athelia revealed no mutations.