Familial clustering of Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder . Evaluation of the few familial cases might provide insight into its aetio logy and pathogenesis. We conducted a survey to identify familial LCH cases . Data on family history, zygosity assessment in twins, clinical and labora tory features, treatment outcome, and present status were collected. Accord ing to variable confidence for twins monozygosity assessment, we termed the se pairs 'presumed monozygotic' (pMZ). Nine families had more than one affe cted relative: five with LCH-concordant twin pairs, four with LCH in siblin gs or cousins. Three twin pairs not concordant for LCH were also studied. O verall, four of five pMZ twin pairs and one of three dizygotic (DZ) pairs w ere concordant for LCH. The pMZ twins had simultaneous and early disease on set (mean age 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminat ed LCH. The three healthy twins tone pMZ, two DZ) remain asymptomatic 0.3, 5.9 and 4.7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental co nsanguinity and the other possible consanguinity. Potential consanguinity w as also present in one of the two families with affected first cousins. Our data support high LCH concordance rates in pMZ twins and add the finding o f LCH concordance in one of three dizygotic pairs studied. Taken together w ith our identification of LCH in siblings and first cousins from known or p ossibly consanguineous families, and with prior reports of three affected p arent-child pairs, the data support a role for genetic factor(s) in LCH. Th e work-up of newly diagnosed patients should include a careful, extensive f amily history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study.