Majeed Syndrome: Five Cases With Novel Mutations From Unrelated Families in India With a Review of Literature.

Abstract

Majeed syndrome (MJS) is an autosomal recessive, systemic autoinflammatory disease (SAID) caused by biallelic loss-of-function variants in the <i>LPIN2</i> gene. It is characterized by early-onset chronic recurrent multifocal osteomyelitis (CRMO), dyserythropoietic anemia, and neutrophilic dermatosis. We analyzed a cohort of uncharacterized Indian patients for pathogenic variants in <i>LPIN2</i> and other genes associated with SAIDs. We performed whole-exome sequencing (WES) for 1 patient and next-generation sequencing (NGS) targeted gene panel for SAIDs in 3 patients. One patient was a referral from neurology after clinical exome sequencing identified a novel variant in <i>LPIN2</i>. We reviewed the literature for all published studies of mutation-positive MJS patients and have summarized their clinical features and disease-causing variants. We describe the largest series of patients with MJS outside of the Middle East. All 5 patients are homozygous for novel, possibly pathogenic variants in the <i>LPIN2</i> gene. Two of these variants are missense substitutions, and 3 are predicted to alter transcript splicing and create a truncated protein. In addition to the classical features of CRMO and anemia, patients exhibited previously unreported features, including abdominal pain, recurrent diarrhea/ear discharge, and erythema nodosum. Patients with MJS may present initially to different specialists, and thus it is important to create awareness in the medical community. In India, consanguinity is a common sociocultural factor in many ethnic communities and an abbreviated NGS gene panel for autoinflammatory diseases should include MJS. The unavailability of interleukin 1 inhibitors in some countries poses a treatment challenge.