Alternative titles; symbols
ORPHA: 1334; DO: 2058;
Cytogenetic location: 2p22.3-p21 Genomic coordinates (GRCh38): 2:31,800,001-47,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p22.3-p21 | Candidiasis, familial, 1, autosomal dominant | 114580 | Autosomal dominant | 2 |
Chronic mucocutaneous candidiasis (CMC) includes a group of rare disorders with altered immune responses, selective against Candida, characterized by persistent and/or recurrent infections of the skin, nails, and mucous membranes, caused by organisms of the genus Candida, mainly Candida albicans (Zuccarello et al., 2002).
Isolated familial chronic mucocutaneous candidiasis is distinct from candidiasis with endocrinopathy (240300).
In myeloperoxidase deficiency (254600), susceptibility to candidiasis may be increased.
Genetic Heterogeneity of Candidiasis
Familial candidiasis-1 (CANDF1) maps to chromosome 2p. CANDF2 (212050) is caused by mutation in the CARD9 gene (607212) on chromosome 9q34.3. CANDF3 (607644), a form restricted to nails of the hands and feet, maps to chromosome 11. CANDF4 (613108) is caused by mutation in the CLEC7A gene (606264) on chromosome 12p13. CANDF6 (613956) is caused by mutation in the IL17F gene (606496) on chromosome 6p12. CANDF7 (614162) is caused by mutation in the STAT1 gene (600555) on chromosome 2q32. CANDF8 (615527) is caused by mutation in the TRAF3IP2 gene (607043) on chromosome 6q21. CANDF9 (616445) is caused by mutation in the IL17RC gene (610925) on chromosome 3p25.
A form of familial candidiasis, previously thought to be isolated and designated CANDF5, has been found to be part of a primary immune deficiency (IMD51; 613953) that includes Staphylococcal skin infections and increased susceptibility to chronic bacterial respiratory infections.
In a family reported by Canales et al. (1969), an 11-year-old boy, his sister, and her daughter had chronic cutaneous candidiasis.
Familial occurrence of CMC was reported by Wells et al. (1972), who described both males and females affected and consanguinity in a number of their pedigrees.
Sams et al. (1979) and Jorizzo et al. (1980) described a family with this disorder with apparent autosomal dominant inheritance. Nine persons in 3 generations were affected. Dermatophytosis, alopecia, loss of teeth, and recurrent viral infections were present in some. Tests of cell-mediated immunity showed total cutaneous anergy in 3 of 8 affected persons. Four of the other 5 had negative lymphocyte transformation and skin tests to candida. The authors made the significant observation that candida skin tests were positive and lymphocyte transformation normal under age 2 years in 2 children with chronic mucocutaneous candidiasis present clinically since the age of 6 months. After age 2, however, these tests became negative. The authors referred to other reports of affected parent and child.
Atkinson et al. (2001) studied an Alabama kindred with an autosomal dominant form of chronic mucocutaneous candidiasis associated with thyroid disease. Four members had both candidiasis and thyroid disease; 5 members, including 1 pair of phenotype-concordant monozygotic twins, had candidiasis only; and 3 members had thyroid disease only. The kindred had first been reported by Montes et al. (1971) in a trial of prolonged oral therapy of amphotericin B. The mother of the patient in that trial had had lifelong, severe CMC and required thyroidectomy at age 30 for euthyroid goiter with no antithyroid antibodies. Hypothyroidism was found in some members of the family, including a man who, in addition to fungal infections of the skin, mouth, and nails, was diagnosed with Riedel thyroiditis, a fibrosing, invasive thyroid disease usually seen in older women (Zimmermann-Belsing and Feldt-Rasmussen, 1994). The disorder was distinguished from APECED (240300) by the mode of inheritance and lack of associated endocrinopathy.
Clinical Variability
Loeys et al. (1999) reported a patient who presented at 5 years of age with a hemiparesis due to a middle cerebral artery infarction. An embolism had originated from a mycotic aneurysm located in the internal carotid artery. Clipping of the aneurysm, after 3 months of antimycotic treatment, followed by sustained treatment with itraconazole and fluconazole, led to a favorable outcome. For several months prior to admission, the patient had been suffering from therapeutically resistant candidiasis of the mouth and nails. Family history revealed chronic mycotic infections of the skin, hair, nails, and mouth in the father and paternal grandmother, suggestive of chronic mucocutaneous candidiasis with an autosomal dominant mode of inheritance.
Ee et al. (2005) reported a 20-year-old man from Singapore with CMC and acne rosacea. Both his mother and dizygotic twin brother were affected with CMC and acne rosacea but less severely. The proband and his brother developed facial erythema with pustules and telangiectasia on the cheeks and nose at ages 17 and 10 years, respectively. Their mother developed acne rosacea only in her forties. Although none of the patients had clinical evidence of an endocrinopathy, laboratory studies of the proband showed a positive result for thyroid microsomal and antiparietal cell antibodies. The proband also had iron deficiency anemia.
Atkinson et al. (2001) performed a whole-genome scan using DNA samples from 20 members of the Alabama family with CMCT and identified a candidate linkage region on 2p. By sampling additional individuals and genotyping supplementary markers, Atkinson et al. (2001) established linkage to a region of approximately 15 cM bounded by D2S367 and D2S2240 and including 7 adjacent markers consistent with linkage. With a penetrance estimate of 0.8, which was based on pedigree and affected status, the peak 2-point lod score was 3.70 with marker D2S2328, and the peak 3-point lod score was 3.82 with marker D2S1788.
Atkinson, T. P., Schaffer, A. A., Grimbacher, B., Schroeder, H. W., Jr., Woellner, C., Zerbe, C. S., Puck, J. M. An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family. Am. J. Hum. Genet. 69: 791-803, 2001. [PubMed: 11517424] [Full Text: https://doi.org/10.1086/323611]
Canales, L., Middlemas, R. O., III, Louro, J. M., South, M. A. Immunological observations in chronic mucocutaneous candidiasis. Lancet 294: 567-571, 1969. Note: Originally Volume II. [PubMed: 4185535] [Full Text: https://doi.org/10.1016/s0140-6736(69)90264-5]
Ee, H. L, Tan, H. H., Ng, S. K. Autosomal dominant familial chronic mucocutaneous candidiasis associated with acne rosacea. Ann. Acad. Med. Singapore 34: 571-574, 2005. [PubMed: 16284681]
Jorizzo, J. L., Sams, W. M., Jr., Jegasothy, B. V., Olansky, A. J. Cimetidine as an immunomodulator: chronic mucocutaneous candidiasis as a model. Ann. Intern. Med. 92: 192-195, 1980. [PubMed: 7352725] [Full Text: https://doi.org/10.7326/0003-4819-92-2-192]
Loeys, B. L., Van Coster, R. N., Defreyne, L. R., Leroy, J. G. Fungal intracranial aneurysm in a child with familial chronic mucocutaneous candidiasis. Europ. J. Pediat. 158: 650-652, 1999. [PubMed: 10445344] [Full Text: https://doi.org/10.1007/s004310051169]
Montes, L. F., Cooper, M. D., Bradford, L. G., Lauderdale, R. O., Taylor, C. D. Prolonged oral treatment of chronic mucocutaneous candidiasis with amphotericin B. Arch. Derm. 104: 45-56, 1971. [PubMed: 5120161]
Sams, W. M., Jr., Jorizzo, J. L., Snyderman, R., Jegasothy, B. V., Ward, F. E., Weiner, M., Wilson, J. G., Yount, W. J., Dillard, S. B. Chronic mucocutaneous candidiasis: immunologic studies of three generations of a single family. Am. J. Med. 67: 948-959, 1979. [PubMed: 316285] [Full Text: https://doi.org/10.1016/0002-9343(79)90635-1]
Wells, R. S., Higgs, J. M., McDonald, A., Valdimarsson, H., Holt, P. J. L. Familial chronic muco-cutaneous candidiasis. J. Med. Genet. 9: 302-310, 1972. [PubMed: 4562433] [Full Text: https://doi.org/10.1136/jmg.9.3.302]
Zimmermann-Belsing, T., Feldt-Rasmussen, U. Riedel's thyroiditis: an autoimmune or primary fibrotic disease? J. Intern. Med. 235: 271-274, 1994. [PubMed: 8120524] [Full Text: https://doi.org/10.1111/j.1365-2796.1994.tb01071.x]
Zuccarello, D., Salpietro, D. C., Gangemi, S., Toscano, V., Merlino, M. V., Briuglia, S., Bisignano, G., Mangino, M., Mingarelli, R., Dallapiccola, B. Familial chronic nail candidiasis with ICAM-1 deficiency: a new form of chronic mucocutaneous candidiasis. J. Med. Genet. 39: 671-675, 2002. [PubMed: 12205111] [Full Text: https://doi.org/10.1136/jmg.39.9.671]