SNP Shot: Genomic Insights

Poikiloderma with neutropenia (PN) is a rare condition affecting both the skin and the immune system. The disorder typically starts with a bumpy rash between 6 and 12 months of age, progressing from the limbs to the trunk and face. Around age 2, the rash fades, leaving behind a characteristic pattern of skin changes: patches of darker and lighter skin (hyperpigmentation and hypopigmentation) mixed with small, visible blood vessels under the skin (telangiectases). This combination of symptoms is referred to as poikiloderma. Other skin manifestations can include thickened skin on the palms and soles (palmoplantar keratoderma), small calcium deposits forming nodules under the skin (calcinosis cutis), especially around joints like knees and elbows or on the ears, and slow-healing skin sores (ulcers). Individuals with PN may also have thick, misshapen nails (pachyonychia), fragile teeth, and reduced bone density.

A key feature of PN is chronic neutropenia, a persistent deficiency of neutrophils. Neutrophils are essential white blood cells that fight infection and contribute to inflammation control. Due to neutropenia, individuals with PN are more susceptible to infections, particularly recurrent sinus infections and pneumonia, especially during early childhood. Many develop bronchiectasis, a condition causing damage to the bronchial tubes, leading to potential breathing difficulties. While infections may become less frequent after childhood, affected individuals often experience chronic cough or reactive airway disease throughout their lives. Reactive airway disease includes conditions like asthma, where the airways narrow abnormally in response to triggers (e.g., smoke, viral infections), causing wheezing and shortness of breath.

Research suggests a possible increased risk of cancer in individuals with PN. However, the precise level of risk remains unclear due to the limited number of diagnosed cases. A few individuals with PN have developed squamous cell carcinoma (a type of skin cancer), myelodysplastic syndrome (MDS, a precancerous blood disorder), or acute myelogenous leukemia (AML, a blood cancer that can develop after MDS).

Some people with PN may also develop distinctive facial features over time. These features can include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), a flattened or sunken midface (midface hypoplasia), a small nose with a depressed nasal bridge, and a protruding chin (prognathism). Short stature and hypogonadotropic hypogonadism (a condition affecting hormone production crucial for sexual development) may also occur.

Inheritance:

PN is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. The parents, who each carry only one copy of the mutated gene, are usually asymptomatic carriers.