Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

Abstract

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9) L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP).

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

“…Immunological anomalies occur occasionally; if unusually frequent or severe infections are present, further studies are indicated 62 . Thrombocytopenia has been reported but is usually non-progressive and asymptomatic 63,64 , and specific testing is not needed.…”

AFF3, a susceptibility factor for autoimmune diseases, is a molecular facilitator of immunoglobulin class switch recombination

“…S1). The GWAS data suggest that AFF3 is associated with both rheumatoid arthritis and T1D (3)(4)(5)(6)(7)(8)(9)(10)(11) and that its expression is restricted to the lymphocytes and brain in mice and humans (12,13). While the function of AFF3 is thought to be related to transcriptional elongation based on the structural and biochemical similarity of AFF3 to AFF1/4 (14), the role of AFF3 in the immune system has not been investigated.…”

“…More than 10 GWAS have identified the AFF3 gene as being associated with autoimmune diseases (3)(4)(5)(6)(7)(8)(9)(10)(11). Although the mRNA expression of AFF3 is known to be restricted to the lymphocytes and brains of mice and humans (12,13), the functions of AFF3 in the immune system have not been studied.…”