STAC3 Disorder

Excerpt

Clinical characteristics: STAC3 disorder is characterized by congenital myopathy, musculoskeletal involvement of the trunk and extremities, feeding difficulties, and delayed motor milestones. Most affected individuals have weakness with myopathic facies, scoliosis, kyphosis or kyphoscoliosis, and contractures. Other common findings are ptosis, abnormalities of the palate (including cleft palate), and short stature. Risk for malignant hyperthermia susceptibility and restrictive lung disease are increased. Intellect is typically normal. Originally described in individuals from the Lumbee Native American tribe (an admixture of Cheraw Indian, English, and African American ancestry) in the state of North Carolina and reported as Native American myopathy, STAC3 disorder has now been identified in numerous other populations worldwide.

Diagnosis/testing: The diagnosis of STAC3 disorder is established in a proband with suggestive clinical findings and biallelic pathogenic variants in STAC3 identified by molecular genetic testing.

Management: Treatment of manifestations: At present, no treatment halts or reverses the manifestations of STAC3 disorder. Treatment of musculoskeletal involvement is symptomatic and ideally provided by a multidisciplinary neuromuscular team to address the following:

1. Occupational and physical therapy needs regarding range of motion and mobility

2. Use of adaptive devices for mobility and activities of daily living

3. Feeding difficulties

4. Speech delays

5. Scoliosis

6. Respiratory insufficiency

Due to the medical comorbidities in STAC3 disorder, decisions regarding type and timing of cleft palate surgery should be determined by a multidisciplinary craniofacial team. Depending on the structure of the managing craniofacial team, interventions for ptosis may be undertaken by an ophthalmologist as part of team care, or as an insertion intervention.

Surveillance: Routine monitoring of growth, musculoskeletal complications (e.g., scoliosis and/or joint contractures), speech development, swallowing function, respiratory function, and educational needs.

Agents/circumstances to avoid: Anesthetic agents with a high risk of triggering malignant hyperthermia.

Genetic counseling: STAC3 disorder is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Unless the reproductive partner of an affected individual also has STAC3 disorder or is a carrier, offspring will be obligate heterozygotes (carriers) for a pathogenic variant in STAC3. Once the STAC3 pathogenic variants have been identified in an affected family member, carrier testing of at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.