Identification of a novel rare genetic disease : “MADaM” syndrome

Mandibuloacral dysplasia syndromes (MAD) are premature aging syndromes belonging to the clinical spectrum of “progeroid laminopathies”, including Hutchinson-Gilford Progeria ( These disorders are associated to nuclear altered morphology and function. Dr. Annachiara De Sandre-Giovannoli and Pr. Nicolas Lévy, with a large national and international consortium, identified that biallelic null mutations of the MTX2 gene, encoding a mitochondrial membrane protein, cause a novel form of MAD, called « MADaM » syndrome. Patients present with a premature aging clinical phenotype very similar to that of Progeria patients, including growth retardation, arterial calcification and severe hypertension, renal glomerulosclerosis, bone resorption and cutaneous anomalies. They show that loss of the protein MTX2 causes several cellular dysfunctions, including resistance to induced apoptosis, increased cell senescence and secondary nuclear morphological defects, establishing a pathophysiological link with premature aging laminopathies and likely explaining common clinical features.

Nature Communications 2020 Sep 11;11(1):4589. doi: 10.1038/s41467-020-18146-9.