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SNOMEDCT: 201144006, 87872006; ICD10CM: L64, L64.9; DO: 0050801;
Cytogenetic location: 3q26 Genomic coordinates (GRCh38): 3:161,000,001-183,000,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3q26 | Alopecia, androgenetic, 1 | 109200 | Autosomal dominant | 2 |
Androgenetic alopecia is characterized by a loss of hair from the scalp that follows a defined pattern (Hamilton, 1951). It occurs in women as well as in men. It is caused by a shortening of the anagen (growth) phase and miniaturization of the hair follicle, which results in the formation of progressively thinner, shorter hair (Bergfeld, 1995). In men, the condition is often referred to as male pattern baldness (MPB) and appears to be androgen-dependent (Hamilton, 1942). The condition is hereditary, and follows a pattern that may be consistent with an autosomal dominant trait (Osborn, 1916).
Linkage evidence for an autosomal locus on 3q26 (AGA1) has been identified (Hillmer et al., 2008). See 300710 (AGA2) for a discussion of X linkage of androgenetic alopecia. A third locus has been found on chromosome 20p11 (AGA3; 612421).
Hamilton (1951) classified pattern baldness and gave incidence figures.
Carey et al. (1993) identified families with polycystic ovaries (PCO; 184700) in females and premature male pattern baldness in males, inherited in an autosomal dominant pattern. The authors postulated that polycystic ovary syndrome may be the female phenotype of premature male pattern baldness.
Early baldness of the ordinary type has been thought to be autosomal dominant in males and to be autosomal recessive in females who transmit the trait if heterozygous but are bald only if homozygous (Osborn, 1916; Snyder and Yingling, 1935). The transmission through many successive generations, as in the descendants of President John Adams, suggests the operation of a single major gene.
Kuster and Happle (1984) reviewed the genetics of MPB and concluded that the Osborn hypothesis had not been thoroughly tested and was thus of questionable validity. In their analysis of 5 previous studies, Kuster and Happle (1984) concluded that a polygenic mode of inheritance was more likely.
Hillmer et al. (2008) presented the results of a genomewide linkage study of androgenetic alopecia in 95 families and linkage fine mapping of 4 regions in an extended sample of 125 families of German descent. The locus with strongest evidence of linkage was mapped to 3q26 (AGA1) with a nonparametric linkage (NPL) score of 3.97 (P = 0.00055). The other 3 regions were in chromosomes 11q22, 18q11, and 19p13.
In studies of 81 affected individuals from 14 Caucasian families in which females had polycystic ovaries and males pattern baldness, Carey et al. (1994) found a single-base change in the 5-prime promoter region of the CYP17 gene (609300), which seemed to modify the expression of the syndrome in some families but could be excluded as the primary genetic defect.
Ellis et al. (1998) found no evidence that the gene for either of the 2 isoforms of the steroid 5-alpha-reductase enzyme (SRD5A1, 184753; SRD5A2, 607306) is involved in the genetics of MPB. From a population survey of 828 healthy families, they identified 58 young bald men (aged 18 to 30 years) and 114 older nonbald men (aged 50 to 70 years) for a case-control comparison. No significant differences were found between cases and controls in allele, genotype, or haplotype frequencies for restriction fragment length polymorphisms of either gene. Furthermore, no clear inheritance pattern of male pattern baldness was observed. A relatively strong concordance for baldness between fathers and sons found in this study was considered inconsistent with simple mendelian autosomal dominant inheritance, since bald sons would be expected to inherit the condition from either the mother or the father in equal proportions. As many as 44 bald sons (i.e., 81.5%) had bald fathers.
Sprecher et al. (2000) assessed the pattern of androgenetic alopecia in 31 healthy male second-degree relatives of patients affected with atrichia with papular lesions (209500) belonging to a large consanguineous kindred. No difference in age at onset or extent of androgenetic alopecia was observed between healthy homozygotes and heterozygous carriers of the mutation in the 'hairless' gene (HR; 602302). Sprecher et al. (2000) concluded that the presence of a deleterious mutation in one allele of the HR gene does not affect the pattern of androgenetic hair loss. To further test the hypothesis that the HR gene may be involved in androgenetic alopecia, Hillmer et al. (2002) systematically screened HR for genetic variability by SSCA in 46 unrelated men with androgenetic alopecia. To test for involvement of HR in the development of androgenetic alopecia, 7 common variants were genotyped in 61 families with 93 affected offspring. The results were analyzed with the transmission/disequilibrium test (TDT). SSCA showed 15 single-nucleotide substitutions: 8 missense mutations, 4 silent mutations, and 3 mutations in exon-flanking intronic sequences. TDT results showed a marginally significant association between androgenetic alopecia and variants 3379-29G/T (P = 0.024) and 2611-68C/T (P = 0.047). These results, however, did not remain significant after applying the conservative Bonferroni correction for multiple testing. Hillmer et al. (2002) concluded that these results did not provide evidence for a strong involvement of HR in the development of androgenetic alopecia, although a minor role could not be fully excluded.
Bergfeld, W. F. Androgenetic alopecia: an autosomal dominant disorder. Am. J. Med. (Suppl. 1A) 98: 95S-98S, 1995.
Carey, A. H., Chan, K. L., Short, F., White, D., Williamson, R., Franks, S. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin. Endocr. 38: 653-658, 1993. [PubMed: 8334753] [Full Text: https://doi.org/10.1111/j.1365-2265.1993.tb02150.x]
Carey, A. H., Waterworth, D., Patel, K., White, D., Little, J., Novelli, P., Franks, S., Williamson, R. Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum. Molec. Genet. 3: 1873-1876, 1994. [PubMed: 7849715] [Full Text: https://doi.org/10.1093/hmg/3.10.1873]
Ellis, J. A., Stebbing, M., Harrap, S. B. Genetic analysis of male pattern baldness and the 5-alpha-reductase genes. J. Invest. Derm. 110: 849-853, 1998. [PubMed: 9620288] [Full Text: https://doi.org/10.1046/j.1523-1747.1998.00224.x]
Hamilton, J. B. Male hormone stimulation is a prerequisite and an incitant in common baldness. Am. J. Anat. 71: 451-480, 1942.
Hamilton, J. B. Patterned loss of hair in man: types and incidence. Ann. N.Y. Acad. Sci. 53: 708-728, 1951. [PubMed: 14819896] [Full Text: https://doi.org/10.1111/j.1749-6632.1951.tb31971.x]
Hillmer, A. M., Flaquer, A., Hanneken, S., Eigelshoven, S., Kortum, A.-K., Brockschmidt, F. F., Golla, A., Metzen, C., Thiele, H., Kolberg, S., Reinartz, R., Betz, R. C., Ruzicka, T., Hennies, H. C., Kruse, R., Nothen, M. M. Genome-wide scan and fine-mapping linkage study of androgenetic alopecia reveals a locus on chromosome 3q26. Am. J. Hum. Genet. 82: 737-743, 2008. [PubMed: 18304493] [Full Text: https://doi.org/10.1016/j.ajhg.2007.11.014]
Hillmer, A. M., Kruse, R., Macciardi, F., Heyn, U., Betz, R. C., Ruzicka, T., Propping, P., Nothen, M. M., Cichon, S. The hairless gene in androgenetic alopecia: results of a systematic mutation screening and a family-based association approach. Brit. J. Derm. 146: 601-608, 2002. [PubMed: 11966690] [Full Text: https://doi.org/10.1046/j.1365-2133.2002.04766.x]
Kuster, W., Happle, R. The inheritance of baldness: two B or not two B? J. Am. Acad. Derm. 11: 921-926, 1984. [PubMed: 6512048] [Full Text: https://doi.org/10.1016/s0190-9622(84)80498-3]
Osborn, D. Inheritance of baldness. Various patterns due to heredity and sometimes present at birth--a sex-limited character-dominant in man--women not bald unless they inherit tendency from both parents. J. Hered. 7: 347-355, 1916.
Snyder, L. H., Yingling, H. C. The application of the gene-frequency method of analysis to sex-influenced factors, with special reference to baldness. Hum. Biol. 7: 608-615, 1935.
Sprecher, E., Shalata, A., Dabhah, K., Futerman, B., Lin, S., Szargel, R., Bergman, R., Friedman-Birnbaum, R., Cohen, N. Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene. J. Am. Acad. Derm. 42: 978-982, 2000. [PubMed: 10827399]