In addition to a SCID phenotype, compound heterozygous and homozygous hypomorphic mutations were identified among six families presenting with a hyper-IgE phenotype, characterized by moderate to severe atopic dermatitis, significant elevations in IgE and connective tissue abnormalities; dysmorphic appearance and neurocognitive impairment were also common to all three patient cohorts. The gene discussed is IGHE; the disease is atopic eczema.