SNP Shot: Genomic Insights

Severe congenital neutropenia (SCN) is a disorder characterized by a heightened risk of recurring infections. Individuals with SCN have a deficiency of neutrophils, a type of white blood cell crucial for fighting infection and managing inflammation. This neutrophil deficiency, known as neutropenia, is present at birth or shortly thereafter, leading to frequent infections from infancy, including infections of the sinuses, lungs, and liver. Affected individuals may also experience fevers, inflamed gums (gingivitis), and skin inflammation. About 40% of those with SCN exhibit reduced bone density (osteopenia), potentially progressing to osteoporosis, a condition causing bones to become increasingly fragile and prone to fractures. Bone problems can arise at any age, from infancy to adulthood, in individuals with SCN.

Around 20% of individuals with SCN develop blood cancers, particularly myelodysplastic syndrome or leukemia, during adolescence.

Some individuals with SCN may have additional health issues, such as seizures, developmental delays, or abnormalities of the heart or genitals.

Inheritance:

Most SCN cases are sporadic, occurring in individuals with no family history of the condition. While some of these cases are linked to specific gene mutations, the cause remains unknown in others. SCN caused by ELANE gene mutations follows an autosomal dominant inheritance pattern, meaning that one copy of the altered gene in each cell is enough to cause the disorder. Mutations in a few other genes that cause SCN are also inherited in an autosomal dominant pattern. When SCN results from HAX1 gene mutations, it is inherited in an autosomal recessive pattern. This means that both copies of the gene in each cell must be mutated. Individuals with an autosomal recessive disorder inherit one copy of the mutated gene from each parent, who are typically carriers without symptoms. Many cases of SCN are caused by genetic mutations inherited in an autosomal recessive manner. In rare instances, SCN is inherited in an X-linked recessive pattern. In these cases, the responsible gene is located on the X chromosome, one of the sex chromosomes. Males (with one X chromosome) need only one altered copy of the gene to be affected. Females (with two X chromosomes) would require mutations in both copies of the gene to develop the disorder. Consequently, males are more frequently affected by X-linked recessive disorders than females. A key characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.