Palmoplantar keratodermas (PPK) comprise a heterogenous group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Hereditary PPKs can be classified into 3 groups: 1) isolated non-syndromic PPKs; 2) complex non-syndromic PPKs associated with other ectodermal defects; and 3) syndromic PPKs associated with extracutaneous manifestations. All types of inheritance have been observed: autosomal dominant, autosomal recessive, X-linked recessive, and mitochondrial. Some of these disorders are restricted to geographic isolates. This review describes the different genetic causes of hereditary syndromic and complex PPKs for which the genes have been identified. The identification of pathogenic variants has consequences in terms of genetic counseling, appropriate medical care and follow-up, especially for PPKs predisposing to hearing loss, cardiomyopathies, benign tumors or carcinomas. In addition, the development of targeted therapies based on pathophysiology of disorders should allow a more effective treatment of these conditions in the near future.
Keywords: AD; AR; CTSC; Cathepsine C; DSC2; DSP; Desmocollin 2; Desmoplakin; EGFR; ENPP1; Epidermal growth factor receptor; GJB2; GJB6; Gap Junction Protein Beta 2; Gap Junction Protein Beta 6; JUP; Junction Plakoglobin; KPP; KPPH; KRT; LOR; LRR; MTBPS2; MTTS1; Membrane Bound Transcription Factor Peptidase; Mitochondrially encoded tRNA serine 1; NACHT; NGS; NRLP1; Next-generation sequencing pour séquençage de nouvelle génération; P53 Apoptosis Effector Related To PMP22; PC; PERP; PPK; R-Spondin 1; RHBDF2; RSPO1-; Rhomboid 5 Homolog 2; SAM and SH3 domain-containing protein 1; SASH1; SERPINA2; SOX; SPL; SRY; SRY box-containing; Serpin Family A Member 2; Sex-determining Region of Y chromosome; Site 2; TAT; TRPV3; Transient Receptor Potential Cation Channel Subfamily V Member 3; Tyrosine aminotransférase hépatique; WNT10A; Wnt Family Member 10A; and PYD domains-containing protein 1; autosomique dominant; autosomique récessif; beta-catenin pathway; desmosomes; ectonucleotide pyrophosphatase/phosphodiesterase 1; keratins; keratoderma; kératine; kératodermie palmoplantaire; kératodermie palmoplantaire héréditaire; loricrine; pachyonychie congénitale; palmoplantar keratoderma; syndrome de papillon-Lefevre.