Autosomal recessive hypotrichosis

Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair (hypotrichosis) on the scalp beginning in infancy. This hair is usually coarse, dry, and tightly curled (often described as woolly hair). Scalp hair may also be lighter in color than expected and is fragile and easily broken. Affected individuals often cannot grow hair longer than a few inches. The eyebrows, eyelashes, and other body hair may be sparse as well. Over time, the hair problems can remain stable or progress to complete scalp hair loss (alopecia) and a decrease in body hair.

Rarely, people with autosomal recessive hypotrichosis have skin problems affecting areas with sparse hair, such as redness (erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular papules that develop around hair follicles, which are specialized structures in the skin where hair growth occurs.

The worldwide prevalence of autosomal recessive hypotrichosis is unknown. In Japan, the condition is estimated to affect 1 in 10,000 individuals.

Autosomal recessive hypotrichosis can be caused by mutations in the LIPH, LPAR6, or DSG4 gene. These genes provide instructions for making proteins that are involved in the growth and division (proliferation) and maturation (differentiation) of cells within hair follicles. These cell processes are important for the normal development of hair follicles and for hair growth; as the cells in the hair follicle divide, the hair strand (shaft) is pushed upward and extends beyond the skin, causing the hair to grow. The proteins produced from the LIPH, LPAR6, and DSG4 genes are also found in the outermost layer of skin (the epidermis) and glands in the skin that produce a substance that protects the skin and hair (sebaceous glands).

Mutations in the LIPH, LPAR6, or DSG4 gene result in the production of abnormal proteins that cannot aid in the development of hair follicles. As a result, hair follicles are structurally abnormal and often underdeveloped. Irregular hair follicles alter the structure and growth of hair shafts, leading to woolly, fragile hair that is easily broken. A lack of these proteins in the epidermis likely contributes to the skin problems sometimes seen in affected individuals.

In some areas of the body, other proteins can compensate for the function of the missing protein, so not all areas with hair are affected and not all individuals have skin problems.

Genetic Testing Information

• Genetic Testing Registry: Wooly hair, autosomal recessive 1, with or without hypotrichosis
• Genetic Testing Registry: Hypotrichosis 6
• Genetic Testing Registry: Hypotrichosis 7

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• HYPOTRICHOSIS 8; HYPT8
• HYPOTRICHOSIS 7; HYPT7
• HYPOTRICHOSIS 6; HYPT6

Scientific Articles on PubMed

• PubMed

• Azeem Z, Jelani M, Naz G, Tariq M, Wasif N, Kamran-Ul-Hassan Naqvi S, Ayub M, Yasinzai M, Amin-Ud-Din M, Wali A, Ali G, Chishti MS, Ahmad W. Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). Hum Genet. 2008 Jun;123(5):515-9. doi: 10.1007/s00439-008-0507-7. Epub 2008 May 7. Citation on PubMed
• Horev L, Tosti A, Rosen I, Hershko K, Vincenzi C, Nanova K, Mali A, Potikha T, Zlotogorski A. Mutations in lipase H cause autosomal recessive hypotrichosis simplex with woolly hair. J Am Acad Dermatol. 2009 Nov;61(5):813-8. doi: 10.1016/j.jaad.2009.04.020. Epub 2009 Sep 18. Citation on PubMed
• Khan S, Habib R, Mir H, Umm-e-Kalsoom, Naz G, Ayub M, Shafique S, Yamin T, Ali N, Basit S, Wasif N, Kamran-Ul-Hassan Naqvi S, Ali G, Wali A, Ansar M, Ahmad W. Mutations in the LPAR6 and LIPH genes underlie autosomal recessive hypotrichosis/woolly hair in 17 consanguineous families from Pakistan. Clin Exp Dermatol. 2011 Aug;36(6):652-4. doi: 10.1111/j.1365-2230.2011.04014.x. Epub 2011 Mar 21. Citation on PubMed
• Kurban M, Wajid M, Shimomura Y, Christiano AM. Mutations in LPAR6/P2RY5 and LIPH are associated with woolly hair and/or hypotrichosis. J Eur Acad Dermatol Venereol. 2013 May;27(5):545-9. doi: 10.1111/j.1468-3083.2012.04472.x. Epub 2012 Mar 5. Citation on PubMed or Free article on PubMed Central
• Schaffer JV, Bazzi H, Vitebsky A, Witkiewicz A, Kovich OI, Kamino H, Shapiro LS, Amin SP, Orlow SJ, Christiano AM. Mutations in the desmoglein 4 gene underlie localized autosomal recessive hypotrichosis with monilethrix hairs and congenital scalp erosions. J Invest Dermatol. 2006 Jun;126(6):1286-91. doi: 10.1038/sj.jid.5700237. Citation on PubMed
• Shimomura Y, Wajid M, Petukhova L, Shapiro L, Christiano AM. Mutations in the lipase H gene underlie autosomal recessive woolly hair/hypotrichosis. J Invest Dermatol. 2009 Mar;129(3):622-8. doi: 10.1038/jid.2008.290. Epub 2008 Oct 2. Citation on PubMed
• Shimomura Y. Congenital hair loss disorders: rare, but not too rare. J Dermatol. 2012 Jan;39(1):3-10. doi: 10.1111/j.1346-8138.2011.01395.x. Epub 2011 Nov 2. Citation on PubMed
• Shinkuma S, Akiyama M, Inoue A, Aoki J, Natsuga K, Nomura T, Arita K, Abe R, Ito K, Nakamura H, Ujiie H, Shibaki A, Suga H, Tsunemi Y, Nishie W, Shimizu H. Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA-PLA1alpha in autosomal recessive hypotrichosis. Hum Mutat. 2010 May;31(5):602-10. doi: 10.1002/humu.21235. Citation on PubMed