SNP Shot: Genomic Insights

Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a genetic disorder impacting both bone development and the immune system. Symptoms of SPENCDI can manifest anytime between infancy and adolescence.

SPENCDI is characterized by several bone issues, including flattened vertebrae (platyspondyly), abnormal long bone ends (metaphyseal dysplasia), and lesions detectable via x-ray on long bones and vertebrae. Problems with cartilage, a key skeletal component during development, further contribute to skeletal issues. Individuals with SPENCDI frequently exhibit areas where cartilage hasn't transformed into bone and may develop benign cartilage tumors (enchondromas). These bone and cartilage abnormalities contribute to short stature in individuals with SPENCDI.

Individuals with SPENCDI experience a variety of immune system dysfunctions. Many exhibit autoimmune reactions, where the immune system mistakenly attacks the body's own tissues and organs. This can result in conditions like thrombocytopenia (low platelet count), hemolytic anemia (premature red blood cell destruction), hypothyroidism (underactive thyroid), or chronic inflammatory diseases like systemic lupus erythematosus or rheumatoid arthritis. Furthermore, affected individuals often have impaired immune cells that struggle to proliferate and fight off infections from bacteria and viruses, leading to frequent fevers and recurring respiratory infections.

Neurological complications can also occur in some SPENCDI patients, including muscle stiffness (spasticity), impaired coordination (ataxia), and intellectual disability. Brain calcifications (abnormal calcium deposits) may also be present.

Due to the complexity of immune system impairments, individuals with SPENCDI often have a reduced lifespan, though survival rates vary considerably.

Inheritance:

SPENCDI follows an autosomal recessive inheritance pattern. This means that an individual must inherit a mutated copy of the responsible gene from *both* parents to develop the condition. The parents, who each carry only one copy of the mutated gene, are usually asymptomatic (do not show signs or symptoms).