Familial clustering of Langerhans cell histiocytosis

Abstract

Summary. Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable con®dence for twins monozygosity assessment, we termed these pairs`presumed monozygotic' (pMZ). Nine families had more than one affected relative: ®ve with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of ®ve pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (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 disseminated LCH. The three healthy twins (one 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 consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected ®rst cousins. Our data support high LCH concordance rates in pMZ twins and add the ®nding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identi®cation of LCH in siblings and ®rst cousins from known or possibly consanguineous families, and with prior reports of three affected parent±child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study.

Immunogenetic Heterogeneity in Single-System and Multisystem Langerhans Cell Histiocytosis

“…The disease is usually regarded as a nonhereditary disorder, but a recent report of familial clustering of LCH cases could support a role of genetic (or environmental) factor(s) in LCH (8). In a large case-control study conducted in North America, an association was found between LCH and thyroid disease as well as a family history of thyroid disease (9).…”

Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?

“…Most compelling are two independent reports demonstrating clonality of pathologic LCs (Willman et al, 1994;Yu et al, 1994). Consistent with a genetic basis for LCH, there are reports of familial clustering and a high degree of concordance among presumed monozygotic twins (Arico et al, 1999). Of course, the presence of recurrent genetic abnormalities in LCH would provide much stronger support for this idea but, because of its rarity, only a handful of surveys have been published and none of these is quite definitive.…”

The Adverse Prognostic Hallmarks in Identical Twins with Langerhans Cell Histiocytosis: A Clinical Report and Literature Review

“…Although the presentations in identical-twin pairs and in sporadic patients with LCH are quite disparate, the proliferating pathologic Langerhans cells share similar morphologies and molecular markers (Arico et al 1999; Badalian-Very et al 2012). Toward the center of the cytoplasm there is a folded nucleus with a prominent nuclear membrane and nucleoli.…”