Salih Myopathy

Excerpt

Clinical characteristics: Salih myopathy is characterized by muscle weakness (manifesting during the neonatal period or in very early infancy) and delayed motor development; children acquire independent walking between ages 20 months and four years. In the first decade of life, global motor performance is stable or tends to improve. Moderate joint and neck contractures and spinal rigidity may manifest in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction manifests between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.

Diagnosis/testing: The diagnosis of Salih myopathy is established in a proband with corresponding clinical phenotype and biallelic pathogenic truncating variants in exons 359, 360, and 361 of TTN identified by molecular genetic testing.

Management: Treatment of manifestations: Care, best provided by a multidisciplinary team, includes stretching exercises and physical therapy; assistive mechanical devices for sitting and ambulation as needed. Education regarding correct posture for lying prone and sitting and Garchois brace when needed for scoliosis. Annual influenza vaccine and available immunizations for respiratory illnesses; aggressive treatment for lower respiratory tract infections. Treat heart failure and cardiac arrhythmia as soon as they are evident. Educate parents/caregivers on symptoms of cardiac manifestations; CPR training for parents/caregivers. Cardiac transplantation may be considered for progressive dilated cardiomyopathy and heart failure refractory to medical therapy. Appropriate technical support in educational settings; social work and family support as needed.

Surveillance: Clinical examination and radiographs as needed for orthopedic complications (e.g., foot deformity, joint contractures, spinal deformity). Annual evaluation of respiratory function beginning at age ten years. EKG, 24-hour Holter EKG, and echocardiogram every six months beginning at age five years. Assess family needs at each visit.

Agents/circumstances to avoid: Ibuprofen in those with evidence of cardiomyopathy and congestive heart failure.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk sibs of an affected individual in order to identify as early as possible those who would benefit from monitoring of motor development and cardiac function so that treatment can be instituted promptly.

Genetic counseling: Salih myopathy is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a TTN truncating variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial TTN pathogenic variants. Once the TTN pathogenic variants have been identified in an affected family member, heterozygote testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.