CLINICAL HISTORY:

Signs and symptoms:  Born with dark blonde scalp hair, which fell out by 3 months of age. She re-grew some hair, but it was never substantial. Otherwise healthy, with normal growth and development.

Previous Treatment:  None.

Other information:  Patient’s younger brother appears to have similar condition but has not been diagnosed. No known familial disorders. Parents are unrelated.

PHYSICAL EXAM:

Normal nails, dentition, eyebrows, and eyelashes. Involving much of the scalp are light blonde, vellus hairs. Some fine, follicularly distributed papules on the scalp.

Normal dentition.

Involving much of the scalp are light blonde, vellus hairs. Some fine, follicularly distributed papules on the scalp.

Note normal eyebrows and eyelashes.

LABORATORY TESTS:

Lead level, vitamin D level, and thyroid studies WNL. Direct microscopy of scalp hair revealed no structural or hair shaft abnormalities. Cytogenetics report revealed a normal female karyotype: 46,XX.

DERMATOHISTOPATHOLOGY:

Scalp biopsy was declined by parents due to the potential for psychological trauma to the patient. Replacement of mature hair follicle structures by follicular cysts filled with cornified material is characteristically seen on scalp histology.

DIFFERENTIAL DIAGNOSIS:

1.   Alopecia universalis
2.   Atrichia with papular lesions
3.   Alopecia totalis
4.   Vitamin-D-dependent rickets
5.   Alopecia areata

SCROLL DOWN FOR ANSWER AND DISCUSSION.

CORRECT DIAGNOSIS:

Atrichia with papular lesions

DISCUSSION:

Atrichia with papular lesions (APL, also known as papular atrichia) is a rare autosomal recessive disorder characterized by complete irreversible hair loss during the first months of life. Hair is then typically absent from the scalp, axillae, and body. A few scattered hairs may remain in the eyelash and eyebrow regions. Multiple keratinous follicular papules appear later in life (generally in the first decade), especially on the face, scalp, and extremities. Individuals affected with APL usually do not show growth or developmental abnormalities. They have normal teeth, nails, hearing, and propensity to sweat. APL is frequently misdiagnosed as alopecia universalis (loss of all scalp and body hair). Vitamin-D dependent rickets also mimics APL, with atrichia in the first few months of life and papules made up of follicular cysts filled with cornified material within the first few years of life.

Linkage to chromosome 8p12 on the human hairless gene (HR) has been implicated as the cause of APL. The HR gene encodes a zinc finger transcription factor protein that is exclusively expressed in brain and skin. Thirty known mutations in the HR gene (including nonsense, missense, deletion, insertion, and splice site compound mutations) have been reported in APL. However, there is very little phenotypic variation despite the various mutations.

Once considered a rare condition, with most reported cases of homozygous mutations in consanguineous families,
increasing reports of novel compound/heterozygous mutations
and sporadic cases in unrelated individuals are being reported. Thus, APL may be more common than previously thought.

Proposed revision of diagnostic criteria include 5 major and 5 minor criteria, where 4 out of 5 major criteria are required to make the diagnosis of APL and the minor criteria are supplementary to the diagnosis. Major criteria include:
- permanent and complete absence of scalp hairs by the first few months of life
- few to widespread smooth, whitish, or milia-like papules on the face, scalp, arms, elbows, thighs, or knees from infancy/childhood
- replacement of mature hair follicle structures by follicular cysts filled with cornified material in scalp histology
- mutation(s) in the human hairless gene (HR) through genetic testing
- clinical and/or molecular exclusion of vitamin-D-dependent rickets
Minor criteria include:
- family history of consanguinity
- absence of secondary axillary, pubic, or body hair and/or sparse eyebrows and eyelashes
- normal growth and development, including normal bones, teeth, nails, and sweating
- whitish-hypopigmented streaks on the scalp
- lack of response to any treatment modality

TREATMENT:

None available.

REFERENCES:

Yip L, Horev L, Sinclair R and A Zlotogorski. Atrichia with Papular Lesions: A Report of Three Novel Human Hairless Gene Mutations and a Revision of Diagnostic Criteria. Acta Derm Venereol 2008;88:346-349.

Additional Comment:

Patient's cytogenetics report also showed an approximate 6 kb gain within chromosome band Xp21.1 (this is a benign copy variant, probably with no significance). To officially make the diagnosis of APL, need parental DNA. Of note, Dr. Angela Christiano at Columbia University researches alopecia, with specific DNA testing of the HR gene. Unfortunately, parents refused both sets of additional genetic tests.

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