Pachyonychia congenita (type I) with mutation in KRT16/6a (Jadassohn-Lewandowski)

The term "Pachyonychia congenita" is used to describe a group of ectodermal dysplasia syndromes, usually with autosomal dominant inheritance and varying degrees of cornification disorders of the skin (keratosis palmoplantaris) and mucous membranes, as well as pronounced nail dystrophies. In pachyonychia congenita (type I), mutations in the keratin genes KRT6b and KRT16.

Pachyonychia congenita is divided into 4 clinical subgroups according to current knowledge (PC1-4):

• Type I: Jadassohn-Lewandowsky type (PC-1; OMIM 167200) - autosomal dominant mutations in the KRT16 or KRT6A genes (chromosome 17q12-q21). To date, 25 mutations in KRT16 have already been associated with PC. 21 mutations are located on exon 1 and 4 mutations are located on exon 6. (Xu Q et al. 2019)
• Type II: Jackson-Lawler type (PC-2; OMIM 167210) - mutations in KRT6b and KRT17, genes encoding the respective keratins and located on chromosome 17q12-q21 as well as on 12q13.
• Type III: (PC-3; OMIM 615726)- Mutations in KRT6a, a gene located on chromosome 12q13.13.
• Type IV: (PC-4; OMIM 61528) - mutations in KRT6b, a gene located on chromosome 12q13.13.

Furthermore, there is a late-manifested type (Pachyonychia congenita tarda) that resembles either the PC-1 type or the PC-2 type.

Incidence: 0.5-1/100,000 population/year.

Predominantly autosomal-dominantly inherited mutations in the keratin genes KRT6a (gene locus: 12q13) as well as KRT16 (gene locus: 17q12-q21); more rarely autosomal-recessive inheritance and spontaneous mutations.

The described mutations of the keratin genes KRT16 affect the helix initiation motif, a functionally significant segment at the beginning of the helical structure of keratin monomers. These are crucial for the undisturbed formation of keratin filaments. This leads to functional deficits of the keratinocytes, e.g. in response to normal mechanical stress.

Keratin mutations cause the keratin filaments to clump together and can no longer interact with other cytoskeletal structures. This results in a reduced mechanical load capacity of the epithelial dressing.

Mostly congenital. Late manifestations between the 10th - 30th year are described according to case reports.

Congenital claw-like, thickened finger and toe nails. Insular or striated palmar, rarely plantar keratoses (PC1), often hyperhidrosis. Circumscribed keratoses on toes, soles, heels, elbows, and knees. Sebostasis and blistering are possible.

Mucosal changes: Whitish, streaky plaques on the tongue, corners of the mouth, oral mucosa and larynx (leukokeratoses see oral leukoplakia).

Congenital onychogryposis

Traumatic nail changes

Twenty-nail dystrophy

Steatocystoma multiplex

Palmoplantar keratoses of other genesis (see below Palmoplantar keratoses)

Epidermolysis bullosa hereditaria

White mucous nevus

Treat circumscribed keratoses, especially palmar and plantar, with salicylic acid-containing plasters (e.g. Guttaplast plasters) in combination with callus planes or salicylic acid-containing or urea-containing formulations such as R215 or R105. For onycholysis, apply highly concentrated urea-containing topical preparations (e.g. 40% urea paste, Onychomal cream, urea paste 40% ). If necessary, use orthopaedic footwear according to the prescription.

Good results are described with acitretin (neotigasone), initially 0.5-1 mg/kg bw/day, maintenance dose 0.2-0.5 mg/kg bw/day. Relatively high dosage seems to be necessary.

Hyperkeratosis of the skin regresses better than nail changes.

Rapamycin (m-TOR inhibitor) showed an improvement of the symptoms with regard to the keratoses.

Abrasion of the nails. If necessary, surgical removal of the nails including the nail bed.

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