Phenotype/genotype relationships in sickle cell disease: a pilot twin study

Area of Science:

• Genetics
• Hematology
• Pediatrics

Background:

• Sickle cell disease (SCD) is a group of inherited red blood cell disorders.
• Understanding the interplay of genetic and non-genetic factors is crucial for managing SCD complications.

Purpose of the Study:

• To investigate the influence of genetic and non-genetic factors on hematology, growth, and clinical features in sickle cell disease.
• To compare the concordance of various parameters between identical twins and sibling pairs with SCD.

Main Methods:

• Studied nine identical twin pairs (six with sickle cell disease, three with sickle cell-haemoglobin C disease).
• Utilized a comparison group of 350 age- and gender-matched sibling pairs with an age difference of <5 years.
• Assessed concordance for numerical data, physical growth parameters, hematological markers, and clinical complications.

Main Results:

• Identical twins exhibited significantly higher correlations than siblings for attained height, weight, fetal hemoglobin, total hemoglobin, mean cell volume, mean cell hemoglobin, and total bilirubin.
• Twins showed concordance in splenomegaly, priapism susceptibility, and menarche onset.
• Other clinical complications displayed discordance in prevalence and severity between twins.

Conclusions:

• Physical growth and hematological characteristics in sickle cell disease are substantially influenced by genetic factors.
• Non-genetic factors contribute to the variability observed in the clinical manifestations and disease severity of sickle cell disease.