SNP Shot: Genomic Insights

Chediak-Higashi syndrome is a multi-system disorder that significantly impacts the immune system. It impairs the function of immune cells, making them less effective at combating pathogens like viruses and bacteria. Consequently, individuals with this syndrome often experience frequent and persistent infections, beginning in infancy or early childhood. These infections are often severe and potentially fatal.

A hallmark of Chediak-Higashi syndrome is oculocutaneous albinism, leading to abnormally light pigmentation of the skin, hair, and eyes. Affected individuals typically present with fair skin and light-colored hair, often exhibiting a metallic shine. Oculocutaneous albinism also results in visual impairments, including reduced visual acuity, involuntary, rapid eye movements (nystagmus), and heightened sensitivity to light (photophobia).

Many individuals with Chediak-Higashi syndrome experience blood clotting abnormalities (coagulation defects), resulting in easy bruising and excessive bleeding. In adulthood, the syndrome can also affect the nervous system, leading to symptoms such as weakness, clumsiness, gait disturbances, and seizures.

Without successful treatment, most children with Chediak-Higashi syndrome progress to the accelerated phase. This severe phase is believed to be triggered by a viral infection. During the accelerated phase, white blood cells (normally responsible for fighting infections) undergo uncontrolled proliferation and infiltrate various organs. This phase is characterized by fever, episodes of abnormal bleeding, overwhelming infections, and organ failure. These complications are typically life-threatening during childhood.

A small subset of individuals with Chediak-Higashi syndrome exhibit a milder form of the condition, manifesting later in life. These individuals with the adult-onset form experience less pronounced pigmentation changes and have a lower likelihood of recurrent, severe infections. However, they face a significant risk of developing progressive neurological problems, including tremors, impaired coordination and balance (ataxia), reduced sensation and weakness in the extremities (peripheral neuropathy), and cognitive decline.

Inheritance:

Chediak-Higashi syndrome follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. The parents, each carrying one copy of the mutated gene, are typically asymptomatic carriers.