Pachyonychia congenita is characterized by onychogryposis, hyperkeratosis of the palms, soles, knees and elbows, tiny cutaneous horns in many areas, and leukoplakia of the oral mucous membranes. Hyperhidrosis of the hands and feet is usually present. Murray (1921) ... Pachyonychia congenita is characterized by onychogryposis, hyperkeratosis of the palms, soles, knees and elbows, tiny cutaneous horns in many areas, and leukoplakia of the oral mucous membranes. Hyperhidrosis of the hands and feet is usually present. Murray (1921) found 7 affected in 3 generations. Kumer and Loos (1935) found 24 affected in 5 generations. McKusick (1971) observed an apparent new mutation with transmission from father to son in a Jewish family. Laryngeal changes requiring tracheostomy for respiratory distress during childhood were reported by Stieglitz and Centerwall (1983) in father and son. Feinstein et al. (1988) classified 168 reported cases into 4 types, of which type IV, present in 7.2% of the cases, had laryngeal lesions, hoarseness, mental retardation, hair anomalies, and alopecia. Paller et al. (1991) described a late-onset form in which typical subungual hyperkeratoses began during the teenage years. Leukokeratosis and keratoderma of the palms and soles were associated. The family history of 3 of the 5 patients was consistent with autosomal dominant inheritance. Gorlin et al. (1976) suggested that 2 distinct syndromes are subsumed under the designation pachyonychia congenita. PC1, the Jadassohn-Lewandowsky type, shows oral leukokeratosis. PC2, the Jackson and Lawler type, has natal teeth and epidermoid cysts (cylindromas), but no oral leukoplakia. Corneal dystrophy may be a feature exclusively of the Jackson-Lawler type. Both disorders are clearly autosomal dominant. On the basis of a study of 13 patients with PC1 or PC2, Terrinoni et al. (2001) concluded that the presence of pilosebaceous cysts following puberty is the best indicator of PC2; prepubescent patients are more difficult to classify due to the lack of cysts. Natal teeth are indicative of PC2, although their absence does not preclude the PC2 diagnosis. Leachman et al. (2005) analyzed clinical, pathologic, and genetic data from the literature in 2 research registries. They found that more than 97% of PC cases exhibited fingernail and toenail thickening, and painful plantar keratoderma. Prospective evaluation of 57 PC patients from 41 families revealed variable clinical findings: hyperhidrosis (79%), oral leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma (60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%), coarse or twisted hair (26%), early primary tooth loss (14%), and presence of natal or prenatal teeth (2%). Stratification of these data by keratin mutation confirmed the increased incidence of cyst formation and natal teeth among PC2 patients, although cysts were more commonly seen in PC1 patients than had previously reported (25-33%). Previously unreported clinical features of PC included development of painful oral and nipple lesions during breastfeeding, copious production of waxy material in ears, and inability to walk without an ambulatory aid (50%). - Pachyonychia Congenita Tarda, Type 1 Pachyonychia congenita with late onset of symptoms has been described by several authors (Paller et al., 1991; Iraci et al., 1993; Lucker and Steijlen, 1995; Mouaci-Midoun et al., 1996; Hannaford and Stapleton, 2000) and has been referred to as pachyonychia congenita tarda. There has been some debate as to whether these late-onset cases represent a separate genetic syndrome or a variant form of PC1. Connors et al. (2001) described a young girl with clinical features of pachyonychia congenita type 1 that was unusual in that the typical skin and nail changes were not noted until the age of 6 years. Direct sequencing of the KRT16 gene revealed a novel lys354 to asn mutation (K354N; 148067.0008) in the central 2B domain of the KRT16 polypeptide. Mutations in this region of KRT16 had not been described, but had been described in homologous regions of KRT14 (148066) in the milder Koebner (131900) and Weber-Cockayne (131800) variants of epidermolysis simplex. It was unclear whether the position of the mutation was sufficient to explain the late-onset phenotype.
In a sporadic case of pachyonychia congenita type 1, Smith et al. (1999) identified heterozygosity for a 3-bp deletion (148067.0001) in the KRT16 gene.
In affected members of a Slovenian family segregating PC1, Bowden et al. ... In a sporadic case of pachyonychia congenita type 1, Smith et al. (1999) identified heterozygosity for a 3-bp deletion (148067.0001) in the KRT16 gene. In affected members of a Slovenian family segregating PC1, Bowden et al. (1995) identified heterozygosity for a 3-bp deletion in the KRT6A gene (148041.0001).