Overlap of Familial Mediterranean Fever and Hyper-IgD Syndrome in an Arabic Kindred

Abstract

Hyperimmunoglobulinemia D Syndrome (HIDS) has rarely been reported in Arabs. Moreover, the simultaneous presence of mutations in MEFV and MVK segregating in the same family is exceptional. We report an Arabic girl presenting since the age of 8-years with two patterns of recurrent episodes of fever, and associated with a spectrum of clinical features suggestive of overlap between familial Mediterranean fever (FMF) and HIDS. Her 19-year old brother presented since the age of 1 year with prolonged episodes of fever and was diagnosed with HIDS at the age of 7 years based on clinical features and homozygosity for p.V377I mutation in MVK. Shorter episodes of fever and abdominal pain more consistent with FMF ensued since the age of 17 years. Genetic testing done for both patients and all other family members revealed simultaneous presence of mutations in MEFV and MVK but with a variable clinical spectrum ranging from asymptomatic to severe manifestations. Both of our patients are homozygous for p.V377I MVK mutation; the girl is a compound heterozygote for p.E148Q/p.P369S/p.R408G and p.E167D/p.F479L MEFV mutations whereas the brother is a compound heterozygote for p.E148Q/p.P369S/p.R408G and p.M680I MEFV mutations. The clinical implications of having more than one mutation in different genes of monogenic autoinflammatory diseases in the same individual are not clear but may explain atypical clinical manifestations such as the overlap features of both FMF and HIDS in this family.

Molecular genetic evaluation of NLRP3, MVK and TNFRSF1A associated periodic fever syndromes

“…Several recent studies have reported the coexistence of MEFV and NLRP3, TNFRSF1A or MVK gene variants that determined possible synergistic effects (Kubota et al., ; Mereuta et al., ; Moussa et al., ; Timerman & Frank, ). Usage of an NGS panel and identification of double heterozygosities may enable the elucidation of new polygenic inheritance models.…”

Clinical and genetic association, radiological findings and response to biological therapy in seven children from Qatar with non‐bacterial osteomyelitis

“…To our knowledge, our patient is the first reported patient with classic FMF features and multifocal inflammatory bone disease. Rare reports of patients with more than one autoinflammatory gene mutation are emerging in the literature . These observations elicited an interest to expand genetic testing for patient 6 and to test the remaining available patients in our group for the possibility of mutations involving other autoinflammatory disorder genes using the clinically available panel test of seven autoinflammatory diseases.…”

“…There are reports of symptomatic improvement and treatment failures with corticosteroids, methotrexate, sulfasalazine, colchicine and azathioprine. There are only a few reports of the use of anakinra and canakinumab in CRMO and Majeed syndrome, with mixed results . We used monthly canakinumab in one patient with Majeed syndrome after the patient developed dyserythropoietic anemia; this treatment resulted in early signs of responsiveness in terms of fewer clinical complaints and improved anemia as early as 3 months after starting the medication.…”

Hyperimmunoglobulin-D Syndrome in Children: A Review Article

“…Therefore, atypical clinical manifestations such as the overlap features of both FMF and HIDS are reported (16).…”