Shwachman-Diamond syndrome
Shwachman-Diamond syndrome is an inherited condition that primarily affects the bone marrow, pancreas, and skeletal system.
Overview
Shwachman-Diamond syndrome is an inherited condition that impacts multiple body systems. The most significant effects are seen in the bone marrow, which produces blood cells, and the pancreas, which is essential for digestion. Skeletal abnormalities are also a common feature of the disorder.
Symptoms
The symptoms of Shwachman-Diamond syndrome are variable and can affect several parts of the body:
- Bone Marrow Dysfunction: Malfunctioning bone marrow often fails to produce enough neutrophils (a type of white blood cell), leading to neutropenia. This increases vulnerability to infections such as pneumonia, otitis media, and skin infections. Less commonly, shortages of red blood cells (causing fatigue and weakness) or platelets (causing bruising and bleeding) occur.
- Pancreatic Insufficiency: Most infants do not produce enough digestive enzymes, leading to difficulty absorbing nutrients. Symptoms include fatty, foul-smelling stools (steatorrhea), slow growth, and failure to thrive.
- Skeletal Abnormalities: Many individuals experience problems with bone formation and growth, particularly in the hips and knees. Low bone density and short stature are common. Some infants are born with a narrow rib cage, which can cause breathing difficulties.
- Other Complications: The condition may affect the liver, heart, endocrine system, eyes, teeth, and skin. Delayed speech and motor skill development have also been reported.
Causes & Risk Factors
The condition is primarily caused by mutations in the SBDS gene, which is involved in the formation of ribosomes—the cellular structures that create proteins. A shortage of functional SBDS protein is thought to impair ribosome formation, though the exact mechanism leading to the syndrome's symptoms remains under investigation.
Other genes, including DNAJC21, EFL1, and SRP54, have also been linked to the condition in a small percentage of cases.
Complications
Individuals with Shwachman-Diamond syndrome face an increased risk of serious blood-related disorders, including:
- Myelodysplastic syndrome (MDS)
- Acute myeloid leukemia (AML)
Inheritance
Most cases are inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell contain mutations. Typically, parents are unaffected carriers. In rare instances, the condition may be inherited in an autosomal dominant pattern, or result from a new (de novo) mutation.