Hints for Genetic and Clinical Differentiation of Adult-Onset Monogenic Autoinflammatory Diseases

Table 1

Summary of the main genetic and clinical features of FMF, TRAPS, CAPS, and MKD.

Disease	Gene locus	Inheritance	Protein	Main clinical features
FMF	MEFV; 16p13.3	AR	Pyrin	Fever, serositis, arthritis generally affecting large joints, erysipelas-like rash, and systemic AA amyloidosis in untreated patients
TRAPS	TNFRSF1A; 12p13	AD	Tumor necrosis factor receptor 1	Fever, migrating erythematous skin rash, muscle pain due to monocytic fasciitis, periorbital edema, arthralgia or arthritis, serosal involvement, and systemic AA amyloidosis in untreated patients
FCAS	NLRP3; 1q44	AD	Cryopyrin	Fever, cold-induced urticaria-like rash, conjunctivitis, and arthralgia
MWS				Fever, urticaria-like rash, conjunctivitis, arthralgia, neurosensorial deafness, and risk of amyloidosis
CINCA				Fever, urticaria-like rash, uveitis, papilledema, deforming arthritis mainly involving large joints, chronic aseptic meningopathy, neurosensorial deafness, and risk of amyloidosis
HIDS	MVK; 12q24	AR	Mevalonate kinase	Fever, polymorphous rash, arthralgia, abdominal pain, diarrhea, lymph node enlargement, splenomegaly, and aphthosis
MEVA				Psychomotor retardation, growth delay, progressive cerebellar ataxia, dysmorphisms, and vision deficits in addition to HIDS features

List of abbreviations: AD—autosomal dominant; AR—autosomal recessive; CINCA—chronic infantile neurologic cutaneous and articular syndrome; FCAS—familial cold autoinflammatory syndrome; FMF—familial Mediterranean fever; HIDS—hyperimmunoglobulinemia D syndrome; MEFV—Mediterranean fever; MEVA—mevalonic aciduria; MKD—mevalonate kinase deficiency; MVK—mevalonate kinase; MWS—Muckle-Wells syndrome; NLRP3—NACHT, LRR, and PYD domain-containing protein 3; TNFRSF1A—tumor necrosis factor receptor super family 1A; TRAPS—tumor necrosis factor-associated periodic syndrome.