PIK3R1-Related Immunodeficiency and SHORT Syndrome
Autosomal dominant
PIK3R1 makes a regulatory part of the PI3K enzyme, which controls cell growth and immune cell signalling. Changes that reduce PI3K signalling cause SHORT syndrome, while specific changes that increase PI3K-delta activity in immune cells cause activated PI3K-delta syndrome 2 (APDS2). Changes may be inherited or arise de novo.
Signs and symptoms
In APDS2, recurrent chest, ear and sinus infections begin in childhood, often with enlarged lymph nodes and spleen, persistent viral infections and some people have a hyper-IgM pattern. Some people also have growth delay. There is an increased risk of lymphoma. SHORT syndrome features are described separately.
What a diagnosis changes
APDS2 is managed by immunology teams, with antibody replacement and antibiotics as needed. Leniolisib, a PI3K-delta inhibitor, is recommended as first-line treatment for significant lymphoproliferative disease, and stem cell transplant is reserved for severe or treatment-refractory cases. Genetic counselling is recommended; each child of an affected person has a 1 in 2 chance of inheriting the change, and relatives can be tested.
Genes analysed
Specific forms also covered
Includes 2 related subtypes ↓Hide subtypes ↑
- immunodeficiency 36 with lymphoproliferation
- SHORT syndrome
