SNOMEDCT: 400059005; ORPHA: 2340, 3406, 79100; DO: 0080751;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q13.3 | ?Keratosis pilaris atrophicans | 604093 | Autosomal recessive | 3 | LRP1 | 107770 |
A number sign (#) is used with this entry because of evidence that keratosis pilaris atrophicans (KPA) is caused by homozygous mutation in the LRP1 gene (107770) on chromosome 12q13. One such family has been reported.
Keratosis pilaris atrophicans (KPA) represents a group of rare genodermatoses characterized by perifollicular keratosis and inflammation that progresses to atrophy and scarring of the facial skin. Keratosis pilaris of extensor surfaces of limbs is a common associated finding. Affected individuals may present with features that overlap between 3 subtypes, keratosis pilaris atrophicans faciei (KPAF), keratosis follicularis spinulosa decalvans (KFSD), and atrophoderma vermiculata (AVA; see 209700) (summary by Klar et al., 2015).
Klar et al. (2015) studied a consanguineous Pakistani family in which 3 sibs and their cousin had keratosis pilaris atrophicans (KPA). Affected family members had normal facial skin at birth, but at approximately 1 year of age lacrimation in response to sunlight or cool air was noted, followed by the development of erythema, nonpurulent follicular papules, and atrophy on cheeks. With age, pit-like areas of follicular atrophy spread to the chin, upper lip, forehead, nasal ridge, and earlobes; the atrophic pits were separated by apparently normal skin. At age 7 to 8 years, the lacrimation stopped, but eyelashes were lost and eyebrows became sparse. All 4 affected children developed atrophic keratosis pilaris on the extensor surface of arms and legs, with the absence of body hair most evident in the postpubertal individuals. The affected children displayed no other ectodermal symptoms or signs, and they had normal psychomotor development, growth, and vision. Histologic analysis of skin biopsies from affected areas of the cheeks showed follicular plugging, comedo formation, and perifollicular lymphocyte infiltration consistent with KPA. Noting that the affected individuals showed features of both AVA and KFSD, the authors designated this to be a mixed type of KPA.
Nazarenko et al. (1999) presented a patient with partial monosomy of 18p caused by a de novo translocation t(Y;18) and a generalized form of keratosis pilaris (keratosis pilaris affecting the skin follicles of the trunk, limbs, and face, i.e., ulerythema ophryogenes). Two-color fluorescence in situ hybridization (FISH) with centromere-specific Y and 18 DNA probes identified the derivative chromosome 18 as a dicentric with breakpoints in p11.2 on both the Y chromosome and chromosome 18. The patient had another normal Y chromosome. This was the third report of an 18p deletion, and the first case of a translocation involving 18p and a sex chromosome, with this genodermatosis. The data suggested that the short arm of chromosome 18 is a candidate region for a gene causing keratosis pilaris. Unmasking of a recessive mutation at the disease locus by deletion of the wildtype allele could be the cause of the recessive genodermatosis. Earlier reports of the 18p deletion in association with keratosis pilaris were provided by Zouboulis et al. (1994) and Horsley et al. (1998).
The transmission pattern of KPA in the family reported by Klar et al. (2015) was consistent with autosomal recessive inheritance.
By autozygosity mapping in a consanguineous Pakistani family with a mixed type of KPA, Klar et al. (2015) identified homozygosity for a region at chromosome 12q (chr12:63,359,011-67,072,557, GRCh37) that segregated with disease, yielding a maximum 2-point lod score of 2.55.
By whole-exome sequencing in 2 affected cousins from a consanguineous Pakistani family with a mixed type of KPA mapping to chromosome 12q, Klar et al. (2015) identified homozygosity for a missense mutation in the LRP1 gene (K1245R; 107770.0002). The mutation segregated fully with disease in the family and was not found in 200 Swedish or 200 Pakistani control chromosomes, in 900 in-house exomes, or in the dbSNP, EVS, ESP, or ExAC databases.
Keratosis pilaris defines a group of cutaneous disorders of ectodermal origin characterized by follicular hyperkeratosis and frequently occurring with ichthyosis or atopy. Ulerythema ophryogenes is classified as one of the types of this genodermatosis (Azambuja et al., 1987). Ulerythema is an erythematous disorder of the skin characterized by the formation of cicatrices and by atrophy; ulerythema ophryogenes is keratosis pilaris affecting the follicles of the eyebrow hairs, associated with erythema, and often leading to scarring and atrophy. The prefix 'ophryo-' refers to the eyebrow.
Azambuja, R., Proenca, N. G., Cardoso, W. V. Ulerythema ophryogenes and folliculitis ulerythematosa reticulata. Hautarzt 38: 411-413, 1987. [PubMed: 3654209]
Horsley, S. W., Knight, S. J. L., Nixon, J., Huson, S., Fitchett, M., Boone, R. A., Hilton-Jones, D., Flint, J., Kearney, L. Del(18p) shown to be a cryptic translocation using a multiprobe FISH assay for subtelomeric chromosome rearrangements. J. Med. Genet. 35: 722-726, 1998. [PubMed: 9733029] [Full Text: https://doi.org/10.1136/jmg.35.9.722]
Klar, J., Schuster, J., Khan, T. N., Jameel, M., Mabert, K., Forsberg, L., Baig, S. A., Baig, S. M., Dahl, N. Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal recessive keratosis pilaris atrophicans. J. Med. Genet. 52: 599-606, 2015. [PubMed: 26142438] [Full Text: https://doi.org/10.1136/jmedgenet-2014-102931]
Nazarenko, S. A., Ostroverkhova, N. V., Vasiljeva, E. O., Nazarenko, L. P., Puzyrev, V. P., Malet, P., Nemtseva, T. A. Keratosis pilaris and ulerythema ophryogenes associated with an 18p deletion caused by a Y/18 translocation. Am. J. Med. Genet. 85: 179-182, 1999. [PubMed: 10406673]
Zouboulis, C. C., Stratakis, C. A., Rinck, G., Wegner, R. D., Gollnick, H., Orfanos, C. E. Ulerythema ophryogenes and keratosis pilaris in a child with monosomy 18p. Pediat. Derm. 11: 172-175, 1994. [PubMed: 8041661] [Full Text: https://doi.org/10.1111/j.1525-1470.1994.tb00575.x]