Keratosis Pilaris and its Subtypes

Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options

Jason F. Wang; Seth J. Orlow

Disclosures

Am J Clin Dermatol. 2018;19(5):733-757. 

In This Article

Genomics

A family history of KP is present in roughly 39% of patients, indicating a potential genetic etiology with autosomal dominant inheritance.[22] In a genomic analysis of 13 consanguineous Pakistani patients with KPA, KP1245R, a novel homozygous missense variant of LRP1, was identified as pathogenic in autosomal recessive KPA and KP.[51] LRP1 has endocytic functions within the LDL family, and its levels are reduced in the fibroblasts of patients with this mutation, as is cellular uptake of its ligand, α2-macroglobulin.[79] There is also evidence that mutations in desmoglein 4 can contribute to the pathogenesis of autosomal recessive KPA.[80]

KPAF tends to be inherited in an autosomal dominant pattern with incomplete penetrance, but sporadic cases have also been documented.[3] AV can also be inherited in an autosomal dominant fashion, but most cases are sporadic.[3,42] There have been a few pedigrees affected by KFSD with the c.1523A > G mutation in the MBTPS2 gene in the literature.[45,81,82] Mutations in this gene also cause ichthyosis follicularis, alopecia, and photophobia syndrome (IFAPS), which shares clinical features with KFSD.[45,81]MBTPS2 also regulates TRPV3, the gene responsible for Olmsted syndrome, which can present with widespread KP.[83,84] The pattern of inheritance varies, as there are reports of X-linked patterns, autosomal dominant patterns, and sporadic patterns.[3,32,46,81,85] While KFSD typically presents in males, there have been reports in females.[86–88] FSD has been shown to be inherited in a primarily autosomal dominant fashion.[89]

The role of genetics in EFFC is unclear. Autosomal recessive inheritance patterns have been observed,[90] and chromosomal instability may also play a role.[91] A family history of KP is common in EFFC, and familial occurrence of EFFC has been reported, supporting a genetic etiology.[54,92,93] Although EFFC affects all races, Asian populations are more likely to be affected.[60] Disease onset ranges between ages 2 and 43 years in reported cases, but EFFC mostly affects adolescents. The male-to-female ratio is about 2:1.

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