has material basis in germline mutation in IL6ST hyper-IgE syndrome hyper-IgE recurrent infection syndrome 4A, autosomal dominant https://github.com/monarch-initiative/mondo/issues/5261 https://www.malacards.org/card/hyper_ige_syndrome_4a_autosomal_dominant_with_recurrent_infections UMLS:C5676920 OMIM:619752 An immunologic disorder characterized by recurrent mainly sinopulmonary infections associated with increased serum IgE. The phenotype is variable, even within families. Some patients have onset of symptoms in early childhood and develop complications, including bronchiectasis or hemoptysis, whereas others have later onset of less severe infections. Immunologic workup usually shows normal leukocyte levels, although some patients may demonstrate alterations in lymphocyte subsets, including T cells. Affected individuals also have variable skeletal abnormalities, including high-arched palate, hyperextensible joints, scoliosis, and bone fractures. The IL6ST mutations are loss-of-function, although the truncated mutant proteins are expressed and interfere with the wildtype protein in a dominant-negative manner by disrupting IL6 and IL11 signaling. GARD:0026449 MEDGEN:1809613 MONDO:0800131