Familial mycosis fungoides: report of 6 kindreds and a study of the HLA system.
BACKGROUND
The familial occurrence of mycosis fungoides (MF) has been reported only in 8 families. Recently, the HLA class II alleles DRB1* 11 and DQB1* 03 have been found to be significantly increased for patients with sporadic MF, suggesting a possible immunogenetic basis for the pathogenesis of this malignancy.


OBJECTIVE
We sought to detect familial occurrences of MF, to describe familial features, and to investigate the possible association or linkage with the HLA system in such cases.


METHODS
The files of 300 patients with MF were reviewed to search for familial occurrence in at least two first-degree relatives. A group of 252 healthy unrelated individuals served as control subjects. Tissue typing for HLA class I was performed using the microlymphocytotoxicity technique. DNA-based analysis for DRB1* and DQB1* alleles was performed using polymerase chain reaction amplification.


RESULTS
Six families comprising 12 Jewish patients (9 male and 3 female) were detected: in 5, two first-degree relatives had MF; and in one, one member had MF and another had parapsoriasis en plaque. There were 5 families with two affected siblings and one family with a parent-child pair. In all but one family, the age of onset, clinical features, and response to therapy were similar to those in sporadic MF. One family, however, was exceptional: both affected siblings were children and both exhibited a similar but unusual morphology in the form of a hypopigmented variant of MF in conjunction with a psoriasiform variant. The allele frequency of HLA DQB1* 03 was found to be significantly greater among the patients than in the control group (66.7% vs 33%, respectively; P = .027), supporting an association of this allele with familial MF. Analysis of the HLA typing in the affected sibling pairs, when grouped together, did not support linkage to the HLA locus because no segregation distortion could be demonstrated ( P = .76).


CONCLUSIONS
Familial aggregation of MF among Israeli Jews may not be as rare as is reflected in the literature. This familial clustering, together with the detection of certain HLA class II alleles with this malignancy (sporadic and familial), suggests that genetic factors may play a role in MF.
Hodak
Emmilia
E
Department of Dermatology, Sackler Faculty of Medicine, Tel-Aviv University, Petah Tiqva, Israel. ehodak@clalit.org.il
Klein
Tirza
T
Gabay
Boaz
B
Ben-Amitai
Dan
D
Bergman
Reuven
R
Gdalevich
Michael
M
Feinmesser
Meora
M
Maron
Lea
L
David
Michael
M
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology
D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen