A case of Myhre syndrome mimicking juvenile scleroderma
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CASE REPORT
Open Access
A case of Myhre syndrome mimicking juvenile scleroderma Barbara Jensen1*, Rebecca James2, Ying Hong1, Ebun Omoyinmi1, Clarissa Pilkington3, Neil J. Sebire4, Kevin J. Howell5, Paul A. Brogan1,3 and Despina Eleftheriou1,3,6
Abstract Background: Myhre syndrome is a genetic disorder caused by gain of function mutations in the SMAD Family Member 4 (SMAD4) gene, resulting in progressive, proliferative skin and organ fibrosis. Skin thickening and joint contractures are often the main presenting features of the disease and may be mistaken for juvenile scleroderma. Case presentation: We report a case of a 13 year-old female presenting with widespread skin thickening and joint contractures from infancy. She was diagnosed with diffuse cutaneous systemic sclerosis, and treatment with corticosteroids and subcutaneous methotrexate recommended. There was however disease progression prompting genetic testing. This identified a rare heterozygous pathogenic variant c.1499 T > C (p.Ile500Thr) in the SMAD4 gene, suggesting a diagnosis of Myhre syndrome. Securing a molecular diagnosis in this case allowed the cessation of immunosuppression, thus reducing the burden of unnecessary and potentially harmful treatment, and allowing genetic counselling. Conclusion: Myhre Syndrome is a rare genetic mimic of scleroderma that should be considered alongside several other monogenic diseases presenting with pathological fibrosis from early in life. We highlight this case to provide an overview of these genetic mimics of scleroderma, and highlight the molecular pathways that can lead to pathological fibrosis. This may provide clues to the pathogenesis of sporadic juvenile scleroderma, and could suggest novel therapeutic targets. Keywords: Scleroderma, Myhre syndrome, SMAD4
Background Myhre syndrome is a genetic disorder often presenting in infancy, caused by a gain of function mutation in the SMAD family member 4 (SMAD4) gene causing progressive, proliferative fibrosis, occurring spontaneously or following trauma, in addition to a unique set of clinical phenotypic features described below [1–4]. Clinical manifestations of Myhre syndrome include: cardiovascular involvement in up to 70% of patients (congenital heart defects, long- and short-segment stenosis of the * Correspondence: [email protected] 1 Infection, Immunity and Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK Full list of author information is available at the end of the article
aorta and peripheral arteries, pericardial effusion, constrictive pericarditis, restrictive cardiomyopathy, and arterial hypertension); respiratory manifestations (choanal stenosis, laryngotracheal narrowing, obstructive airway disease, or restrictive pulmonary disease); gastrointestinal symptoms (pyloric stenosis, duodenal strictures, severe constipation); hearing loss, mild to moderate development delay, dysmorphic features and skin involvement (skin sclerosis, particularly involving the
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