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

OBJECTIVE: Majeed syndrome (MJS) is an autosomal recessive, systemic autoinflammatory disease (SAID) caused by biallelic loss-of-function variants in the LPIN2 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 LPIN2 and other genes associated with SAIDs. METHODS: 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 LPIN2. We reviewed the literature for all published studies of mutation-positive MJS patients and have summarized their clinical features and disease-causing variants. RESULTS: 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 LPIN2 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. CONCLUSION: 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.

Macrodystrophia Lipomatosa: A Single Large Radiological Study of a Rare Entity.

INTRODUCTION: We present one of the largest case series of Macrodystrophia lipomatosa, a rare congenital disorder of localized gigantism characterized by overgrowth of all the mesenchymal elements, predominantly involving the fibroadipose tissue. AIMS: To detail the radiological features, pattern of distribution, associated conditions and to suggest an appropriate terminology to describe the condition. METHODS AND MATERIAL: It is a retrospective study. Data from PACS server dating from 2000 and 2018 was used. The cases with isolated enlarged limb or digit/digits with or without nerve involvement were included in the study. STATISTICAL ANALYSIS USED: Frequency and percentage were used for analysis of categorical variables. RESULTS: A total of 31 cases was included for the final analysis, out of which 19 were males and 12 were females. Unilateral limb involvement was seen in 30 cases. The most common pattern identified was the 'nerve territory oriented' type in 28 cases confined to the hand or foot, 'diffuse or pure lipomatous' type in one case and mixed type was seen in two cases. The most common nerve territory involved was along the median nerve in the upper limb and along the medial plantar nerve in the lower limb. Neural involvement was seen in 16 cases of the upper limb and 10 cases of the lower limb. Syndactyly was seen in two cases, polydactyly in one case and symphalangism in one case. CONCLUSIONS: A diagnosis of macrodystrophia lipomatosa can be confidently made in cases with congenital isolated limb or digit/digits enlargement with or without fibrolipohamartoma of nerve. Radiographs and ultrasound are sufficient along with clinical examination to make accurate diagnosis. MRI is useful for assessing the extent and for planning surgery.