Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling

Frontiers in Pediatrics

article

Nidia Moreno-Corona¹  Marina Cavazzana¹  Laurence Perrin⁴  Anne Durandy¹  Saba Azarnoush⁴  Sven Kracker¹  Loïc Chentout¹  Lucie Poggi¹  Romane Thouenon¹  Cecile Masson¹  Melanie Parisot⁵  Lou Le Mouel⁴  Capucine Picard¹  Isabelle André¹ 

[1] Université de Paris, Imagine Institute;Laboratory of Human Lymphohematopoiesis;Necker Hospital, Biotherapy and Clinical Investigation Centre—APHP;Hospital Robert Debré;Institut Imagine-Structure Fédérative de Recherche Necker, Université de Paris;Necker Hospital, Pediatric Hematology-Immunology and Rheumatology Unit;Paris Hospital, Study Center for Primary Immunodeficiencies—APHP

关键词: APDS2;    PI3K signaling;    PIK3R1;    primary immunodeficiency;    neurodevelopmental impact;   

DOI  :  10.3389/fped.2021.688022

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Activated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene responsible for an alternative splice product and a shortened protein. The clinical presentation of APDS2 patients is highly variable, ranging from mild to profound combined immunodeficiency features as massive lymphoproliferation, increased susceptibility to bacterial and viral infections, bronchiectasis, autoimmune manifestations, and occurrence of cancer. Non-immunological features such as growth retardation and neurodevelopmental delay have been reported for APDS2 patients. Here, we describe a patient suffering from an APDS2 associated with a Smith–Magenis syndrome (SMS), a complex genetic disorder affecting, among others, neurological manifestations and review the literature describing neurodevelopmental impacts in APDS2 and other PIDs/monogenetic disorders associated with dysregulated PI3K signaling.

【 授权许可】

CC BY