Spinal Muscular Atrophy, X-Linked Infantile

Clinical characteristics X-linked infantile spinal muscular atrophy (XL-SMA) is characterized by congenital hypotonia and areflexia and evidence of degeneration and loss of anterior horn cells (i.e., lower motor neurons) in the spinal cord and brain stem. Often congenital contractures and/or fractures are present. Intellect is normal. Life span is shortened because of progressive ventilatory insufficiency resulting from chest muscle involvement. Diagnosis/testing The diagnosis of XL-SMA is based on clinical findings; evidence of degeneration and loss of anterior horn cells in the spinal cord and brain stem; normal SMN1 molecular genetic testing; and family history consistent with X-linked inheritance. UBA1 is the only gene currently known to be associated with XL-SMA. Management Treatment of manifestations: Assure adequate caloric intake by caloric supplementation and/or gastrostomy feedings as necessary; manage constipation with diet; provide rigorous pulmonary toilet, supplemental oxygen, and noninvasive ventilatory support; discuss "do not attempt to resuscitate" status with the family before respiratory failure occurs. Orthopedic consultation and physical and occupational therapy to manage contractures. Prevention of secondary complications: Precautions against infection. Surveillance: Routine evaluations by a multidisciplinary team, including neurologic evaluation; assessment of pulmonary function, caloric intake, and weight gain; evaluation for scoliosis and/or kyphosis. Genetic counseling XL-SMA is inherited in an X-linked manner. Carrier females have a 50% chance of transmitting the pathogenic variant with each pregnancy. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will usually not be affected. Affected males do not reproduce. Carrier testing for family members at risk and prenatal testing for at-risk pregnancies are available if the UBA1 pathogenic variant has been identified in the family.