MedGen

Immunodeficiency-90 with encephalopathy, functional hyposplenia, and hepatic dysfunction (IMD90) is a autosomal recessive complex immunologic disorder with systemic manifestations in addition to primary immunodeficiency. Affected individuals usually present in infancy or early childhood with recurrent fevers and bacterial or viral infections associated with central nervous system symptoms, including irritability, drowsiness, variable seizures, and white matter abnormalities on brain imaging. There is also liver involvement and functional hyposplenism, causing increased susceptibility to invasive pneumococcal infection, which may be fatal. Susceptibility to viral infections likely results from impaired interferon immunity, and bacterial infections likely result from splenic dysfunction. A subset of patients have congenital cardiac malformations. Most individuals demonstrate developmental delay and speech delay. Laboratory findings in affected individuals are similar to those seen in autoimmune lymphoproliferative syndrome (ALPS; 601859), including high-circulating CD4-/CD8-/TCR-alpha-beta+ (double-negative) T-cell (DNT) counts, and elevated IL10 (124092) and FASL (TNFSF6; 134638) levels, but the clinical features are somewhat different from ALPS: massive lymphadenopathy and autoimmune features are not observed in IMD90 (summary by Bolze et al., 2010, Savic et al., 2015 and Kohn et al., 2020). [from OMIM]

Multiple types of congenital heart defects-8 (CHTD8) is characterized by cardiac septal defects, double-outlet right ventricle, unbalanced complete atrioventricular canal, and valvular anomalies, as well as vascular anomalies including dextroposition of the great arteries, anomalous pulmonary venous return, and superior vena cava to left atrium defect. Patients may also exhibit laterality defects, including dextrocardia, atrial isomerism, dextrogastria, left-sided gallbladder, and intestinal malrotation (Zaidi et al., 2013; Granadillo et al., 2018). [from OMIM]

A persistent left superior vena cava (PLSVC) that drains into the left atrium instead of the right atrium via the coronary sinus, resulting in a right to left sided shunt. [from HPO]