Current review of pediatric Fas-associated death domain protein deficiency: expanding clinical and therapeutic perspectives.

FADD

Pathogenic FADD variants with defective lymphocyte apoptosis, dysregulated T-cell proliferation and elevated soluble FAS ligand and interleukin-10

This systematic literature review (PubMed, Cochrane, Scopus to 2 July 2026, with independent screening and data extraction) retained ten articles describing 18 children with FADD deficiency. Parental consanguinity was reported in 10 of 12 patients (83.3%) and median age at onset was 0.8 years, with fever-related encephalopathy, lymphoproliferation and invasive pneumococcal disease as the main presentations. Double-negative T cells were elevated in 9 of 10 patients, and the most common variant was c.350G>A, followed by c.315T>G. Six patients (33%) died, mostly in the context of pneumococcal infection, and no deaths were reported among patients with a lymphoproliferative phenotype or among the 2 hematopoietic stem cell transplant recipients.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Ten articles for 18 patients: the synthesis describes an ultra-rare disease and allows no therapeutic conclusion, transplantation being documented in only 2 children. Its practical use is to flag the clues (recurrent febrile encephalopathy, liver involvement, consanguinity) that should prompt exome/genome sequencing and immunological work-up. The review protocol is not stated as registered in the abstract.

Analysis by Dr Thibaut Benquey