The autosomal dominantly inherited periodontal EDS (pEDS) is characterized by severe, early onset periodontitis. Clinical symptoms start in childhood with extensive gingivitis leading to destruction of the periodontium and premature tooth loss in adolescence. Other clinical features include pretibial hyperpigmentation, acrogeria, vulnerable skin and gums, abnormal scarring, generalized joint hypermobility, and easy bruising. Rupture of arteries and internal organs and CNS involvement in the form of microangiopathy and leukoencephalopathy have also been described in individual cases.
In 2003, a candidate region was located on chromosome 12p13.1, but no gene was identified. In 2016, complementary exome analysis of 19 families identified pathogenic variants in C1R in 15 families and in C1S in two families. The C1R and C1S genes, which are directly adjacent in region 12p13.1, encode the C1r and C1s subunits of the complement pathway. The proteins form a heterotetramer that combines with six C1q subunits. The pathogenic variants identified so far lead to intracellular retention of the complement complex and endoplasmic reticulum enlargement.
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