Atrichia with Papular Lesions

Alternative Names

  • APL
  • Papular Atrichia
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WHO-ICD-10 version:2010

Diseases of the skin and subcutaneous tissue

Disorders of skin appendages

OMIM Number

209500

Mode of Inheritance

Autosomal recessive

Gene Map Locus

8p21.3

Description

Atrichia with papular lesions (APL) is a rare autosomal recessive form of inherited alopecia. Males and females are equally affected and present with a distinct pattern of total hair loss on scalp, axilla and body. Normal hair is present at birth in most APL patients, which they lose shortly after birth. This form of hair loss is irreversible and the histology is consistent with an absence of mature hair follicles. In addition to total atrichia, APL patients also present with papules and follicular cysts filled with cornified material. Patients are essentially devoid of eyebrows and eyelashes.

Mutations in the hairless (HR) gene are responsible for this condition.

Molecular Genetics

HR is a putative single zinc-finger transcription factor protein. HR has been shown to function as corepressor of multiple nuclear receptors, including thyroid hormone receptor (TR), the retinoic acid receptor-related orphan receptors (ROR) and the vitamin D receptors (VDR) and interacts with histone deacetylases (HDACs). HR knock-out mouse models reveal that HR regulates the timing of epithelial cell differentiation in both the epidermis and hair follicle.

APL remains frequently misdiagnosed as its phenocopy, the putative autoimmune disorder alopecia universalis. However, since the establishment of hairless (HR) gene mutations as the cause of this condition, several patients previously assumed to suffer from alopecia universalis have been subsequently diagnosed with APL.

Epidemiology in the Arab World

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Other Reports

Oman

Kenue and Al-Dhafri (1994) reported a large Omani family of 22 members (male: female ratio of 1:1.4) over six generations with isolated congenital atrichia. Examination of the fifteen individuals alive revealed absent hair from the scalp and eyebrows, absent pubic and axillary hair, and sparse eyelashes on the upper eyelid in 10 subjects. It was reported by the mothers that all children were born with fine hair which was lost after two months of life. No other ectodermal defects were found as there was sweating from all parts of the body denoting normal sweat glands. There was no report of heat intolerance, papular lesions, milia, palmo-plantar keratoderma, or teeth and nails abnormalities. The subjects' growth was normal, there was no mental retardation, and they were not socially discriminated against, as all members of the tribe were related because of multiple consanguinity and they all led a normal life. With charting of the family pedigree, autosomal recessive inheritance was found to be the mode of inheritance and pseudo-dominance or quasidominance was observed only once. Histological examination of skin biopsy revealed complete absence of hair follicles, arrector pili muscle, and sebaceous glands, while the eccrine glands were normally distributed and no other structural abnormality was detected. Kenue and Al-Dhafri (1994) concluded that multiple consanguinity in this tribe had enhanced the manifestation of this trait.

Palestine

In five Palestinian families of Arab origin with atrichia with papular lesions, Zlotogorski et al. (1998) reported a homozygous deletion mutation, 2147delC, in exon 9 of the HR gene that led to a frameshift and premature termination.

In affected individuals of a large consanguineous Arab Palestinian family with congenital atrichia, Ahmad et al. (1999) identified a complex homozygous deletion in exon 3 of the HR gene consisting of a 1-bp deletion (C) at nucleotide 1256 and a 21-bp deletion at nucleotide 1261. Together, the mutations led to a frameshift and premature termination. Obligate carriers in the family were heterozygous for the mutation.

Zlotogorski et al. (2002) proposed revised clinical criteria for APL based on their personal observation of nine Arab families and retrospective analysis of other families described in the literature. These features include family history with autosomal recessive inheritance and possible consanguinity; atrichia at birth or shedding of normal scalp hair several months after birth with failure to regrow; appearance of skin papules (most commonly on the face, under the midline of the eye, and on the extremities) within the first year of life; sparse eyebrows and eyelashes; lack of secondary axillary, pubic, or body hair; whitish hypopigmented streaks on the scalp; normal nails, teeth, and sweating; normal growth and development; and failure of any treatment modality to restore hair growth. Additionally, Zlotogorski et al. (2002) reported the identification of a novel missense mutation in the hairless (hr) gene from a family of Arab Palestinian origin that exhibits the pathognomonic features of atrichia with papular lesions.

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