CORRECT DIAGNOSIS:
Atrichia with papular lesions
DISCUSSION:
Atrichia with papular lesions (APL), also known as papular atrichia, is a rare autosomal recessive disorder marked by complete and irreversible hair loss within the first months of life. Affected individuals typically exhibit a lack of hair on the scalp, axillae, and body, with only a few scattered hairs remaining in the eyelash and eyebrow regions. As the individual ages, particularly during the first decade of life, multiple keratinous follicular papules develop, primarily on the face, scalp, and extremities. Despite these manifestations, individuals with APL usually do not present with growth or developmental abnormalities and have normal teeth, nails, hearing, and sweat production. APL is frequently misdiagnosed as alopecia universalis, which involves the loss of all scalp and body hair. Additionally, vitamin D-dependent rickets may mimic APL, presenting with similar atrichia and papular lesions in early childhood.
The condition has been linked to chromosome 8p12 and the human hairless gene (HR), which encodes a zinc finger transcription factor protein expressed exclusively in the brain and skin. To date, thirty mutations in the HR gene have been identified in APL cases, including nonsense, missense, deletion, insertion, and splice site mutations. Despite the variety of mutations, there is minimal phenotypic variation among affected individuals. Previously considered rare, APL has seen an increase in reported cases, including novel compound and heterozygous mutations, as well as sporadic instances in unrelated individuals, suggesting that it may be more common than once thought.
Revised diagnostic criteria for APL include five major and five minor criteria. To confirm a diagnosis, at least four out of the five major criteria must be met, while the minor criteria serve as supplementary indicators. Major criteria encompass: a permanent and complete absence of scalp hair by the first few months of life; the presence of smooth, whitish, or milia-like papules on the face, scalp, arms, elbows, thighs, or knees from infancy or childhood; replacement of mature hair follicle structures by follicular cysts filled with cornified material in scalp histology; identification of mutations in the HR gene through genetic testing; and clinical or molecular exclusion of vitamin D-dependent rickets. Minor criteria include: a family history of consanguinity; absence of secondary axillary, pubic, or body hair, along with sparse eyebrows and eyelashes; normal growth and development, including normal bones, teeth, nails, and sweating; the presence of whitish-hypopigmented streaks on the scalp; and a 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: The 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.
