Incongruent Phenotypic Expression of Autosomal Dominant Hyper IgE Syndrome (AD-HIES) in a Mother and Son

Abstract

AD-HIES has multifarious effects on multiple systems. Although variable expressivity has been described, no reports detail the course of immediate family members with the AD type. Reviewed documented clinical course and studies conducted at WRNMMC and NIH. Mother and son shared the 1909 G-A mutation in the SH2 domain of STAT3. They had near identical clinical courses from birth through infancy, including classic AD-HIES manifestations such as eczema and pulmonary infections; however, their courses subsequently diverged. The mother developed pneumatoceles and bronchiectasis and required a partial lobectomy by three years of age. Diagnosed with AD-HIES at 8 years old, she started SCIG. In early adulthood, her large pneumatoceles became chronically infected with aspergillus, mycobacterium abscesses, and stenotrophomonas. She underwent bilateral lung transplant at age 27 and developed a diaphragmatic aspergilloma resistant to standard antifungal therapies. Two years later, aspergilloma was identified involving her right pulmonary artery causing hypoxia. Isovuconazole led to improvement, but her lung function diminished requiring continuous oxygen. The patient’s son started replacement SCIG and prophylactic antibiotics by the first year of life. His pulmonary and cutaneous complications were mild after infancy. Although, he has small stature and characteristic AD-HIES facies, his course has been relatively benign on treatment. This is the first reported case highlighting marked variable expressivity in AD-HIES of affected immediate family members. The divergent clinical courses may have been influenced by early diagnosis, initiation of SCIG and prophylaxis, and suggests that providers should consider early testing of AD-HIES patients’ offspring.