Genetic and Clinical Heterogeneity in Transgressive Palmoplantar Keratoderma

Abstract

To the EditorTransgressive hyperkeratosis is a phenomenon that may occur invarious forms of palmoplantar keratoderma (PPK). It consists ofhyperkeratosis spreading from the palms and soles across the line oftransgredience onto the dorsa of the fingers, the toes, the hands andthe feet, the flexor aspects of the wrists and the heels. In particular,transgressive PPK is a feature of autosomal recessively inheriteddisorders such as Naxos disease (PPK with cardiac abnormalities,OMIM #601214), Papillon–Lefe`vre syndrome (PPK with period-ontopathia, OMIM #245000), and Mal de Meleda (OMIM#248300). Mal de Meleda (MDM), or keratosis palmoplantaristransgrediens of Siemens, was first reported in 1826 on the island ofMeleda, now Mljet, in Croatia. It has since been reported inpatients from other European countries, North Africa, the Nearand the Middle East, Chile, India, Laos, and Taiwan. Onset of thedisorder is in early infancy before 1 y of age with diffuse PPK andtransgressive keratosis. There is no associated involvement of otherorgans. Histopathologically, hyperorthokeratosis and acanthosis areseen as well as foci of parakeratosis (Frenk et al, 1996). Some otherfeatures, in which environmental factors may play a role, arefacultative and variable. They are hyperkeratotic scaly lesions ofcobblestone appearance over the knees and elbows called ‘lichenoidplaques’, nail abnormalities, knuckle-pads, perioral erythema,hyperhidrosis, and pseudo-ainhum. Some but not all patientsshow a marked progression of most features of the disease. A ratherbroad spectrum of clinical presentations is characteristic of MDMand it has been argued that the disorder may be geneticallyheterogeneous (Frenk et al, 1996; Lestringant et al, 1997). In 1998, alocus for MDM was described on chromosome 8q24-qter in twoconsanguineous families from Algeria (Fischer et al, 1998). Byhomozygosity mapping, the authors localized the gene to a 5 cMinterval telomeric to D8S1727 (Fig 1). Since then, a third Algerianfamily mapping to the same region has been reported (Bouadjar etal, 2000). Recently, we have confirmed and refined the localizationof a gene for MDM on chromosome 8q24-qter in one Palestinianfamily and two families from the United Arab Emirates.