Autosomal Dominant Keratoderma, Ichthyosiform Dermatosis and Elevated Serum Beta-Glucuronidase

Abstract

Five patients in a large pedigree with autosomal dominant palmoplantar keratoderma and/or an ichthyosiform dermatosis were studied. Biopsies of the keratoderma, a remote hyperkeratotic plaque on an arm and the ichthyosis all revealed the same histopathologic changes including hyperkeratosis with round retained nuclei. All 5 patients had elevated serum beta-glucuronidase activity. The significance of beta-glucuronidase in this and other skin diseases is discussed.

The Molecular Pathology of Progressive Symmetric Erythrokeratoderma: A Frameshift Mutation in the Loricrin Gene and Perturbations in the Cornified Cell Envelope

“…Furthermore, we have analyzed the impact of this mutation on cornified cell envelope formation at the ultrastructural level, as well as its effect on crosslinking and rigidification of the protein (see below). Although clinically it appeared that this patient had unequivocal diagnostic features of PSEK, we initiated molecular analysis of the loricrin gene on the basis of more subtle clinical and histological similarities with a form of palmoplantar keratoderma known as "Vohwinkel syndrome" (Vohwinkel 1929; Camisa and Rossana 1984;Camisa et al 1988), in which we elsewhere had identified a different loricrin mutation (Maestrini et al 1996). These similarities included palmoplantar hyperkeratosis with a honeycomb appearance, pseudoainhum, and ichthyotic lesions on other body sites, although the PSEK cases had significantly more widespread and striking erythematous hyperkeratotic plaques.…”

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…92,93 Recent studies on genotype-phenotype correlation distinguish the TTD syndromes associated with ichthyosis of delayed onset or accompanied with collodion membrane from other forms of TTD. 94 Diseases relatively new in the list of ichthyoses are loricrin keratoderma, also referred to as Camisa variant of Vohwinkel keratoderma (Fig 4, C ), [95][96][97] the cerebral dysgenesiseneuropathyeichthyosisePPK syndrome, 98 the arthrogryposiserenal dysfunctionecholestasis syndrome, 99-101 the mental retardationeenteropathye deafnesseneuropathyeichthyosisekeratodermia syndrome, 102 the ichthyosisehypotrichosisesclerosing cholangitis syndrome (also known as neonatal ichthyosis sclerosing cholangitis syndrome), 103-105 the ichthyosis hypotrichosis syndrome (Fig 5, I ) 106 and its allelic variant congenital ichthyosisefollicular atrophodermaehypotrichosisehypohidrosis syndrome, 107,108 and keratosis lineariseichthyosisecongenital sclerosing keratoderma (Fig 4, F ). 109,110 Erythrokeratodermia variabilis (EKV), [111][112][113] which is characterized by migratory erythematous patches and more fixed, symmetric hyperkeratotic plaques often with palmoplantar involvement (Fig 4, B), is genetically heterogeneous and can in 50% to 65% of cases 114 be caused by mutations in GJB3 coding for the gap junction protein connexin 31, 115 or GJB4 coding for connexin 30.3.…”

Structural and Functional Consequences of Loricrin Mutations in Human Loricrin Keratoderma (Vohwinkel Syndrome with Ichthyosis)

“…Clinically, loricrin keratoderma exhibits a characteristic, honeycomb-like, palmo-plantar keratoderma; generalized fine-scaling; hyperkeratotic knuckle pads on the dorsal surface of the fingers; and constricting bands encircling the fingers and/or toes (pseudoainhum) (Vohwinkel, 1929;Camisa and Rossana, 1984;Camisa et al, 1988;Maestrini et al, 1996;Armstrong et al, 1998;Takahashi et al, 1999;O'Driscoll et al, 2002). Whereas insertional mutations that result in aberrant, elongated C-terminal domains of one loricrin allele are found in loricrin keratoderma (Maestrini et al, 1996), another hyperkeratotic skin disorder, keratoderma hereditaria mutilans (syn.…”