Clinical heterogeneity in families with multiple cases of inborn errors of immunity.

BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve.

Rapid Assessment of Avoidable Blindness in Kurdistan, Iran.

PURPOSE: To determine the magnitude and causes of blindness and visual impairment (VI) in Kurdistan, using the Rapid Assessment of Avoidable Blindness methodology. METHODS: In this population-based cross sectional study, 99 clusters were selected through probability proportional to size sampling. Visual acuity (VA) was measured using a standard tumbling "E" chart. Ophthalmologists examined participants with VA < 6/18 in both eyes. The cause of VI in the better eye or the most treatable cause was considered as the primary cause of VI. RESULTS: A total of 3203 (response rate: 92.4%) individuals aged 50 years and older participated, of whom 1657 (51.7%) were female. The standardized prevalence of blindness, severe visual impairment (SVI), and moderate visual impairment (MVI) based on available correction (presenting VA) were 2.1% (1.5-2.6), 1.7% (1.2-2.2), and 9.6%(8.4-10.8), respectively. The proportion of avoidable causes of blindness, SVI, and MVI were 58.1%, 78.4%, and 83.4%, respectively. The most common cause of blindness and SVI was cataract (27.4% and 60.8% respectively), followed by age-related macular degeneration (25.8% and 13.7%, respectively). The leading causes of MVI were uncorrected refractive errors (RE) (37.2%) and cataract (33.6%). CONCLUSION: The prevalence of blindness in the study population seems comparable to the region. According to our results, blindness, SVI, and MVI were mostly due to avoidable causes. Cataract and refractive errors are the principal causes of blindness and VI in Kurdistan.