Genetic hair disorders
Genetic hair disorders


Many of the genes causing hair shaft defects have recently been documented.  Although genetic hair shaft abnormalities are uncommon in general trichology practice, new information about genetic causes has allowed for a better understanding of the underlying pathophysiologies.

A number of autosomal dominant, autosomal recessive and X-linked single gene disorders are characterised by hair abnormalities. Hair shaft abnormalities encompass a group of congenital or acquired alterations which involve the hair shaft. They usually lack macroscopic features, which would enable easy diagnosis in medical practice.


Three independent researchers compiled a literature review encompassing 159 articles within the last 50 years that describe genetic hair disorders. They grouped these disorders into different categories:

Hypotrichosis: A hair regeneration error caused by a defect in the hair cycle and anchoring of shaft in the skin. One example of this condition is hypertrichosis simplex. This is a disease characterized by diffuse hair thinning with wiry twisted scalp hair. It has an autosomal dominant inheritance. This means that one faulty copy of DNA from the father or the mother is enough to cause the disease.

Treatment of hypertrichosis

Pilot study investigating treatment of hypotrichosis. a pilot clinical trial where the scalp of four patients was treated topically with gentamicin for 6 months, demonstrating significant improvement as ascertained by the Severity of Alopecia Tool score [1].

Genetic hair disorders

Acquired trichorrhexis nodosa in a 17 year old male after hairspray and UV exposure.  Polarised hair showing shaft fracture in multiple areas (×200 magnification) [2].

Hair shaft disorders: This group is further divided into two main categories according to the fragility of the hair. For example, argininosuccinic aciduria is an example of a hair shaft disorder with increased fragility. This is an inborn error of urea synthesis due to the deficiency of the argininosuccinic lyase enzyme. Babies are born with normal hair, but untreated cases can develop a condition called trichorrhexis nodosa.

In trichorrhexis nodosa, there is a microscopic appearance of fractures with splaying out of individual cortical cells from the main body of the hair shaft. This absence of the argininosuccinic lyase enzyme causes the build-up of waste that affects different systems causing serious consequences such as mental retardation.

Trichorrhexis nodosa can also be acquired due to heat, chemical or mechanical damage.   Hereditary woolly hair is another example of a hair shaft disorder. It involves a mutation in the keratin gene. The hair is short, kinked, and tightly curled.

Ectodermal dysplasias: The ectoderm is the outermost layer of cells of an embryo. If this layer is affected in early development, whatever develops from this layer of cells is affected.

These are disorders characterised by abnormalities in the teeth, hair, nails, sweating function, and other ectoderm derived glands like the mammary gland or anterior pituitary gland.

However, hair is the most affected appendage. Missense mutations in the gap junction β6 gene (GJB6) cause a type of ectodermal dysplasia called Clouston syndrome. Hair is short, thin, and sparse at infancy and progresses to total alopecia at puberty.

Ectodermal dysplasias hair abnormalities

Left image. Photomicrograph of normal hair (ordinary light). Right image.photomicrograph of ED hair (ordinary light). The texture of hair in ectodermal dysplasias  is more open and lattice-like [3].

Trichorhinophalangeal syndrome

Typical characteristics of trichorhinophalangeal syndrome. There is no established treatment for this genetic condition [4].

Trichorhinophalangeal syndrome: This is a group of two autosomal dominant genetic diseases (TRPS I and TRPS II) diagnosed by a triad of ectodermal features, distinct facial and skeletal abnormalities. Hair is fine, sparse, slow-growing, and not very pigmented in male pattern baldness, with the recession of the frontotemporal hairline and thinning of hair diameter.

Soon after puberty, one-third of males are nearly or completely bald, while women usually keep most of their hair but have a high frontal hairline. Some patients might present with sparse lateral eyebrows and eyelashes.

Atrichia with papular lesions: This is a rare autosomal recessive disease which means the genes you got from both your parents are defective. It presents with irreversible alopecia of the scalp, eyebrows, axillary, and pubic hair, which starts a few months after birth. It is associated with development keratin cysts over the body.

Atrichia with papular lesions.  A rare autosomal recessive disorder resulting in complete and irreversible hair loss shortly after birth. [5].


Hair loss in children and adults represent a diagnostic and therapeutic challenge for a medical practitioner.  A detailed history including family history and physical examination of hair and other appendages such as nails, sweat glands, and sebaceous glands with the use of dermoscopic devices and biopsy all provide valuable clues to establish a correct diagnosis. Understanding the pathophysiology of genetic hair defects will allow for better comprehension of possible treatment options and prognosis.


  1. Peled A, Samuelov L, Sarig O, Bochner R, Malki L, Pavlovsky M, Pichinuk E, Weil M, Sprecher E. Treatment of hereditary hypotrichosis simplex of the scalp with topical gentamicin. British Journal of Dermatology. 2020 Jul;183(1):114-20.
  2. Gari SA. A case of acquired trichorrhexis nodosa after applying new hair spray. Journal of the Saudi Society of Dermatology & Dermatologic Surgery. 2013 Jul 1;17(2):73-5.
  3. Gold RJ, Scriver CR. Properties of hair keratin in an autosomal dominant form of ectodermal dysplasia. American journal of human genetics. 1972 Sep;24(5):549.
  4. Jeon, J., Kim, J.H., & Oh, C. (2014). Trichorhinophalangeal syndrome type I–clinical, microscopic, and molecular features. Indian journal of dermatology, venereology and leprology, 80 1, 54-7.
  5. Paradisi M, Chuang GS, Angelo C, Pedicelli C, Martinez‐Mir A, Christiano AM. Atrichia with papular lesions resulting from a novel homozygous missense mutation in the hairless gene. Clinical and Experimental Dermatology: Experimental dermatology. 2003 Sep;28(5):535-8.