Segmental progeroid syndromes

Cellular and organismal aging is one of the most complex biological process, and one of the few which ultimately affects every human being. Hereditary syndromes with clinical signs of premature aging, also known as Segmental progeroid syndromes (SPS), are rare hereditary diseases in which the affected individuals show signs of premature aging in more than one organ or type of tissue. These fascinating syndromes, somewhat mimicking physiological aging, are characterized by broad clinical and genetic heterogeneity.

Typical signs of premature aging in SPS is the premature onset of the following symptoms or disorders:

• Graying/loss of hair
• Hearing loss
• Cataracts
• Scleroderma-like skin changes
• Type 2 diabetes mellitus
• Osteoporosis
• Atherosclerosis and coronary heart disease
• Various malignant tumors

For more than 15 years, we have been working on the identification and functional characterization of new genetic causes of segmental progeroid syndromes. In close collaboration with the International Registry of Werner Syndrome and The Progeria Research Foundation, we have identified and functionally characterized several novel monogenic causes for these extremely exciting, clinically and genetically very heterogeneous group of diseases (e.g. SPRTN, MDM2, LEMD2, POLR3A, TOR1AIP1, MTX2...).

Elucidating the genetic and molecular causes of these special diseases continues to be the central theme of the Institute. Furthermore, we strongly believe that the understanding of disease pathology of SPS will shed light on the molecular basis of general aging processes in humans.