Haim-Munk Syndrome

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Haim-Munk syndrome

Definition

Haim-Munk syndrome is an extremely rare genetic disorder similar to Papillion-Lefevre syndrome. Features include callous patches of skin on the palms of the hands and the soles of the feet, long pointy fingers, and degeneration of the tissues that surround and support the teeth.

Description

Haim-Munk syndrome is characterized by red, scaly thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis) that are apparent at birth along with frequent pus-producing (pyogenic) skin infections, overgrowth of the fingernails and toenails (onychogryphosis), and degeneration of the gums and bone surrounding the teeth (periodontosis) beginning in childhood. The severe and ongoing periodontosis usually causes the baby teeth to fall out prematurely, and often results in the loss of the permanent adult teeth as well.

In 1965, researchers Haim and Munk reported findings similar to Papillion-Lefevre syndrome in four siblings from an inbred Jewish family that originated from Cochin, India, on the Malabar Coast and later migrated to Israel. Features that are alike in both Papillion-Lefevre syndrome and Haim-Munk syndrome include skin abnormalities and severe periodontitis. These disorders are considered alternate forms of the same genetic mutation. There are a number of additional features reported in Haim-Munk syndrome that include long, thin, pointed fingers (arachnodactyly), bone loss in the fingers or toes (acroosteolysis), abnormal changes of the nails, and a claw-like deformity of the hands.

Haim-Munk syndrome is also known as Cochin Jewish disorder or congenital keratosis palmoplantaris.

Genetic profile

Haim-Munk syndrome is a homozygous expression of an autosomal recessive trait. Among palmoplantar keratoderma disorders, only Papillion-Lefevre syndrome and Haim-Munk syndrome are associated with the premature loss of teeth. It is suspected that Haim-Munk syndrome could be genetically different from common forms of palmoplantar keratoderma that are linked to the cytokeratin gene families.

Preliminary findings suggest that DNA markers other than keratin genes are responsible for the Haim-Munk syndrome. In 1997, genotype data in affected individuals found that the gene mutations in Haim-Munk syndrome were not due to a gene defect in either type I or type II keratin gene clusters on chromosomes 12 and 17, markers common to other palmoplantar keratoderma conditions.

Because Papillion-Lefevre syndrome and Haim-Munk syndrome present different symptoms than palmoplantar keratoderma disorders, both genetic syndromes are thought to be related to specific bacterial infections in those with palmoplantar keratoderma.

The cause of Papillion-Lefevre syndrome is a mutation in the cathepsin C gene resulting in periodontal disease and palmoplantar keratosis. Haim-Munk syndrome is thought to be a variant clinical expression of Papillion-Lefevre syndrome that is caused by defects in the cathepsin C gene as well.

A study in 2000 reported a mutation of cathepsin C (exon 6, 2127AﬁG) that changes a highly conserved amino acid in the cathepsin C peptide. This suggests that Haim-Munk syndrome and Papillion-Lefevre syndrome are alternate forms of defects in the cathepsin C gene. The study also notes that the basis for the difference in clinical expression (symptoms) of these two syndromes caused by the mutated cathepsin C gene is not known.

Demographics

The estimated occurrence of Papillion-Lefevre syndrome, of which Haim-Munk is an extremely rare variant, is considered one to two persons per million. There appears to be no variance by gender. While Papillion-Lefevre syndrome cases have been identified throughout the world, Haim-Munk syndrome has only been described among descendants of an inbred Jewish family originally from Cochin, India, who migrated to Israel.

Signs and symptoms

The two major manifestations of Haim-Munk syndrome are dermatological abnormalities and juvenile periodontitis.

Individuals identified with the Haim-Munk syndrome show more severe skin abnormalities than groups with Papillion-Lefevre syndrome. Extensive palmoplantar hyperkeratosis typically begins within the first two to three years of life. At birth the palms and soles are bright red in color and then progress to a callused and scaly appearance. As the patient gets older the disease often involves thick scaly patches on the entire front and back area of the hands and feet, as well as the elbows and knees.

A typical pattern of periodontis with Haim-Munk syndrome is as follows: initially the deciduous (baby) teeth appear at the normal time but the gums proceed to swell and bleed. Usually all the deciduous teeth fall out by age four, the mouth then heals and the secondary teeth begin to appear, severe gingival inflammation develops and the majority, or all, of the permanent teeth often fall out by age 15.

Individuals with Haim-Munk syndrome may also have some of the following signs and symptoms:

wasting (atrophy), or thickening, of the nails
a deformity of the fingers called arachnodactyly—abnormally long, thin, tapered fingers and toes
lack of normal blood flow to the extremities that results in numbness and tingling in the fingers and/or toes. It also can cause loss of bone tissue at the ends of the fingers and/or toes (acroosteolysis)
a curve of the bones in the hands causing claw-like features
flat feet (pes planus)
recurrent pus-forming (pyogenic) skin infections

Diagnosis

There are no published diagnostic criteria for Haim-Munk syndrome. Researchers use clinical examination of inbred Jewish Cochin descendents to confirm the presence of Haim-Munk. Diagnosis of Papillion-Lefevre syndrome is confirmed by red, thick callused skin on the palms and soles at birth and dental problems that are usually present by age five.

Affected individuals are diagnosed with Haim-Munk syndrome when all of the following features are present:

palmoplantar keratoderma
thick, rough, and scaly patches of skin on the forearms and legs
severe early onset periodontitis
arachnodactyly
abnormal changes of the nails

Radiology is used to view the thin and tapering bone deformities in the fingers and dental problems associated with Haim-Munk syndrome.

Genetic testing can confirm the mutation of the cathepsin C gene. Genotyping for polymorphic DNA markers (D11S1887, D11S1367, and D11S1367) are used to identify the presence of the cathepsin C gene mutations associated with Haim-Munk syndrome.

Treatment and management

Treatments include extraction of the teeth and use of dental prosthesis, or dentures. Medications are also used to treat skin lesions associated with this disorder.

Prognosis

A normal life span has been reported for individuals with Haim-Munk syndrome. Loss of the baby teeth may occur by age six and loss of the permanent teeth by age 15; however, general health is not impaired and dentures are well tolerated.

Resources

BOOKS

Winter, Robin M., and Michael Baraitser. Multiple Congenital Anomalies, A Diagnostic Compendium. London: Chapman and Hall Medical, 1991.

PERIODICALS

Hart, T. C., et al. "Haim-Munk Syndrome and Papillion-Lefevre Syndrome Are Allelic Mutations in Cathepsin C." Journal of Medical Genetics 37 (2000): 88-94.

Hart, T. C., et al. "Localization of a Gene for Prepubertal Periodontitis to Chromosome 11q14 and Identification of a Cathepsin C Gene Mutation." Journal of Medical Genetics 37(2000): 95–101.

Stabholz, A., et al. "Partial Expression of the Papillion-Lefevre Syndrome in 2 Unrelated Families." Journal of Clinical Periodontology (1996): 764–69.