Haim-Munk Syndrome

A number sign (#) is used with this entry because of evidence that Haim-Munk syndrome (HMS) is caused by homozygous mutation in the gene encoding cathepsin C (CTSC; 602365) on chromosome 11q14.

Mutations in the CTSC gene also cause Papillon-Lefevre syndrome (PLS; 245000) and aggressive periodontitis-1 (170650).

Description

Haim-Munk syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, severe periodonitis, arachnodactyly, acroosteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers (summary by Hart et al., 2000).

Clinical Features

Among members of a small community of Jews from Cochin, India (so-called 'Black Jews'), Haim and Munk (1965), Smith and Rosenzweig (1967), and Puliyel and Sridharan Iyer (1986) described a rare syndrome of congenital palmoplantar keratosis, pes planus, onychogryphosis, periodontitis, arachnodactyly, and acroosteolysis. Although in some ways the disorder suggested the Papillon-Lefevre syndrome, the nail involvement and other associated features suggested that this was a distinct disorder. (Puliyel and Sridharan Iyer (1986) noted that the patients reported by Smith and Rosenzweig (1967) were related to the patients of Haim and Munk (1965). Also, Hacham-Zadeh et al. (1978) referred to the disorder as Papillon-Lefevre syndrome and cited Gorlin et al. (1976) as considering it a clinical variant of PLS.) Flat feet occurred in the persons with keratosis but not in unaffected sibs.

Hart et al. (1997) compared and contrasted Papillon-Lefevre syndrome and Haim-Munk syndrome. Both syndromes have severe early-onset periodontitis with loss of both dentitions, palmoplantar keratosis, and autosomal recessive inheritance. PLS also has calcification of dura mater and increased susceptibility to infections. Haim-Munk syndrome also has arachnodactyly, acroosteolysis, and onychogryphosis. Both disorders combine severe periodontitis with palmoplantar hyperkeratosis.

Inheritance

Puliyel and Sridharan Iyer (1986) found 20 persons with Haim-Munk syndrome in 9 sibships over 4 generations of an inbred kindred. The pattern was entirely consistent with autosomal recessive inheritance. There was no instance of parent-to-child transmission and the parents were consanguineous in many cases.

Molecular Genetics

Because of the phenotypic overlap between HMS and PLS, and the finding of mutations in the CTSC gene in patients with PLS, Hart et al. (2000) studied 50 members of 4 sibships of the Cochin isolate with HMS and identified a missense mutation in the CTSC gene (602365.0006) at a highly conserved residue segregating with the disease. A shared common haplotype was found surrounding the locus in affected individuals, suggesting that they inherited the mutation from a single common ancestor and confirming recessive inheritance of HMS. In addition, Hart et al. (2000) found a nonsense mutation (602365.0007) at the same codon in a Turkish family with PLS, confirming that HMS and PLS are allelic.