Familial Rosai-Dorfman Disease D76.3

Familial Rosai-Dorfman disease, also known as Faisalabad histiocytosis (FHC/MIM 602782) is classified as an autosomal recessively inherited form of histiocytosis that has large overlaps with Rosai-Dorfman disease (RDD).

Mutations in the SLC29A3 gene, which encodes a nucleoside transporter, underlie the familial form of the disease (Morgan NV et al. (2010). Mutational analysis of candidate genes identified biallelic germline mutations in SLC29A3 in the FHC family and in two families with familial RDD (Morgan NV et al. 2010). SLC29A3 encodes an intracellular equilibrative nucleoside transporter (hENT3) with affinity for adenosine.

Furthermore, germline mutations in SLC29A3 have also been described in two rare autosomal recessive disorders with overlapping phenotypes:

• H syndrome (MIM 612391), characterized by cutaneous hyperpigmentation and hypertrichosis, hepatomegaly, cardiac abnormalities, hearing loss, and hypogonadism (Elbarbary NS et al. 2013)
• and
• PHID syndrome (pigmented hypertrichosis with insulin-dependent diabetes mellitus).

Rosai-Dorfman disease is a rare histiocytic disorder that most commonly presents as bilateral cervical lymphadenopathy in children and young adults. It occurs quite predominantly sporadically, and in very rare cases, familial occurrence has been demonstrated. In a significant proportion of patients, the disease occurs extranodally. It was classified as part of the "R group" of histiocytoses by the Histiocyte Society in 2016. Cutaneous Rosai-Dorfman disease is considered a distinct disease entity that falls into the "C group" of histiocytoses according to this classification system (Bruce-Brand C et al. 2020).

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