CDSN – Hypotrichosis Simplex of the Scalp

Hypotrichosis simplex of the scalp (HSS) is a rare autosomal dominant non-syndromic alopecia characterized by progressive scalp hair loss from early childhood. The disorder was genetically mapped to chromosome 6p21.3, leading to the identification of heterozygous CDSN variants as causative for HSS ([PMID:12754508]).

A landmark study in three unrelated families demonstrated nonsense mutations in CDSN, with truncated corneodesmosin aggregating in the superficial dermis and at hair follicle peripheries, implicating a dominant-negative mechanism ([PMID:12754508]).

In a six-generation Mexican pedigree, a nonsense mutation (Y239Ter) in exon 2 of CDSN co-segregated perfectly with disease, absent in 300 control chromosomes, and localized within a 40-amino-acid cluster of stop variants, reinforcing a dominant-negative effect ([PMID:16307662]).

A report of peeling skin disease with compound heterozygous CDSN mutations highlighted that monoallelic c.598C>T (p.Gln200Ter) carriers manifest HSS, strengthening the link between heterozygous truncating CDSN variants and scalp-restricted hair loss ([PMID:31663161]).

Most recently, an 8-year-old boy with HSS carrying a CDSN mutation showed significant hair regrowth following treatment with botanical extracts plus minoxidil, suggesting potential therapeutic approaches for corneodesmosin-mediated hair loss ([PMID:39902296]).

Collectively, five unrelated probands with heterozygous nonsense CDSN variants, perfect segregation in a multi-generation pedigree, and concordant histopathological findings establish a strong gene-disease relationship. Key take-home: CDSN truncating variants cause HSS via a dominant-negative mechanism, enabling molecular diagnosis and guiding therapeutic development.

References

• Nature Genetics • 2003 • Hypotrichosis simplex of the scalp is associated with nonsense mutations in CDSN encoding corneodesmosin. PMID:12754508
• The British Journal of Dermatology • 2005 • A non-sense mutation in the corneodesmosin gene in a Mexican family with hypotrichosis simplex of the scalp. PMID:16307662
• The Journal of Dermatology • 2020 • Mutations in the CDSN gene cause peeling skin disease and hypotrichosis simplex of the scalp. PMID:31663161
• Frontiers in Genetics • 2024 • Treatment of hypotrichosis simplex of the scalp with the combination of botanic extracts and minoxidil: a case report. PMID:39902296

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