STAC3 disorder, also known as Native American myopathy, is a rare inherited condition that primarily affects skeletal muscles from birth, classifying it as a congenital myopathy. While initially identified in individuals from the Lumbee Native American tribe in North Carolina, it can affect individuals from any ethnic background worldwide, despite its higher prevalence in this specific population.
Genetic Cause of STAC3 Disorder
STAC3 disorder stems from mutations in the STAC3 gene. This gene provides instructions for making the STAC3 protein, which plays a role in the contraction of skeletal muscles. Muscle contractions are initiated by changes in the concentration of ions within muscle cells.
The STAC3 protein assists in triggering the release of calcium ions inside muscle cells for muscle contraction. It interacts with two structures in muscle cells, the dihydropyridine receptor (DHPR) and ryanodine receptor 1 (RYR1), which are crucial for calcium ion movement. A disruption in this calcium ion release prevents muscles from contracting normally, leading to the muscle weakness observed in STAC3 disorder.
The inheritance pattern for STAC3 disorder is autosomal recessive. This means an individual must inherit two altered copies of the STAC3 gene, one from each parent, to develop the condition. Parents who carry one altered copy of the gene are typically asymptomatic carriers.
Key Characteristics and Symptoms
Congenital Myopathy
Individuals with STAC3 disorder often present with muscle weakness (myopathy) and poor muscle tone (hypotonia) from birth. In infants, this manifests as “floppiness,” reduced head control, and a weak cry. This muscle weakness can also lead to difficulties with feeding and swallowing in early infancy and delayed development of motor skills, such as sitting, crawling, standing, and walking.
Characteristic Facial Features
Many affected individuals exhibit distinctive facial features. These can include drooping eyelids (ptosis), sunken cheeks, and a mouth often held open with downturned corners. Other observed facial characteristics include a small lower jaw (micrognathia) and an opening in the roof of the mouth (cleft palate).
Skeletal and Orthopedic Issues
Beyond muscle weakness, individuals with STAC3 disorder frequently experience skeletal and orthopedic concerns. These can include congenital joint deformities (contractures), such as clubfoot. As they grow, there is also a tendency to develop abnormal spinal curvatures like scoliosis (side-to-side) or kyphosis (forward rounding), often combined as kyphoscoliosis.
Other Health Considerations
Another health consideration for individuals with STAC3 disorder is an increased susceptibility to malignant hyperthermia. This is a severe reaction to certain anesthetic drugs used during surgery or other invasive procedures. The reaction typically involves a dangerously high body temperature, rigid muscles, and a rapid heart rate.
Diagnosis and Evaluation
Diagnosis of STAC3 disorder typically begins with a thorough clinical evaluation, based on characteristic symptoms and physical findings. The presence of congenital muscle weakness, distinct facial features, and musculoskeletal anomalies often prompts further investigation.
The definitive diagnosis of STAC3 disorder is confirmed through molecular genetic testing. This involves a blood test that specifically looks for mutations within both copies of the STAC3 gene. Sequence analysis is a common method used to detect these small genetic changes.
While genetic testing is the gold standard, other supportive tests may be used to assess the extent of muscle involvement or rule out other conditions. These can include a muscle biopsy, which examines a small sample of muscle tissue under a microscope, or electromyography (EMG), which evaluates the electrical activity of muscles. These additional tests provide supplementary information but do not replace definitive genetic confirmation.
Managing the Condition
Management of STAC3 disorder focuses on providing supportive care and maximizing an individual’s function and overall quality of life, as there is currently no cure. A multidisciplinary team approach is typically employed, involving various specialists to address diverse needs.
Physical therapy is a core component of management, aiming to improve muscle strength, enhance mobility, and prevent or manage joint contractures. Therapists use exercises, stretching, and sometimes serial casting or splinting to maintain range of motion. Occupational therapy assists individuals in developing strategies and using adaptive devices for daily activities, such as feeding and dressing, with greater independence.
Speech therapy is also important for addressing feeding difficulties, swallowing issues, and speech delays commonly associated with the disorder. Therapists may work on strengthening oral motor muscles and developing communication strategies. Ongoing monitoring for orthopedic complications like scoliosis is also necessary, and surgical intervention may be considered if spinal curvature progresses.
Respiratory complications also require close attention, including restrictive lung disease due to muscle weakness affecting breathing. Regular respiratory function testing and, in some cases, ventilatory support may be required. Due to the susceptibility to malignant hyperthermia, medical alert information is crucial to ensure specific anesthetic agents are avoided during any surgical procedures.