Shwachman Syndrome

At a glance

A rare congenital defect characterized by exocrine pancreatic insufficiency with neutropenia (60% of cases) and growth retardation. Other features may include recurrent and fatal infections, aplastic anemia, leukemia, skeletal abnormalities (metaphyseal dysostosis, thoracic dystrophy), hepatic failure, and ichthyotic skin changes.

Synonyms

Shwachman-Diamond Syndrome; Burke Syndrome; Shwachman-Bodian Syndrome.

History

Named after Harry Shwachman, US pediatrician in 1964.

Incidence

Approximately 1:50,000 live births.

Genetic inheritance

Autosomal recessive but may occur sporadically.

Pathophysiology

A multiorgan condition due to mutation of SBDS gene on 7q11.21. Reduction in pancreatic exocrine function that is partly a result of fatty infiltration of the pancreas; evidenced by low or absent amylase, lipase and trypsin activity resulting in malabsorption, and the need for enzyme supplementation. Endocrine pancreatic function not affected. Skin sweat test is normal. Bone marrow has varying degrees of hypoplasia resulting in intermittent neutropenia and thrombocytopenia. Neutrophil chemotaxis is impaired.

Diagnosis

Based on clinical scenario in addition to evidence of pancreatic exocrine insufficiency, intermittent or persistent neutropenia and thrombocytopenia, and abnormal neutrophil chemotaxis. Hypoplastic bone marrow may be present.

Clinical aspects

Initially, neonates may present with failure to thrive, diarrhea, feeding difficulties, and hypotonia. Growth retardation persists into adulthood. Although pancreatic exocrine function is abnormal, endocrine function is normal. Motor and speech development are invariably delayed and intelligence quotient low. Skeletal abnormalities are common and include metaphyseal dysplasia in long bones, knees, wrists, ankles, and vertebrae. Clinodactyly or duplication of the thumb has been described. Ribs are frequently short, resulting in a narrow thoracic cavity. This frequently improves with age. Chest wall compliance is reduced and lung compliance is normal. Forced expiratory volume at 1 second (FEV1) and forced vital capacity (FVC) are usually reduced. Renal tubular dysfunction may be present. Myocardial fibrosis and cardiomegaly have been described and may make patients extremely sensitive to chemotherapy-induced cardiotoxicity. Leukemic transformation has been described in 5 to 33% of patients.

Precautions before anesthesia

Hematologic: evaluate for evidence of pancytopenia and correct abnormalities preoperatively. Pulmonary function testing particularly in patients with chest wall abnormalities. Cardiac function: particularly echocardiogram following chemotherapy. Airway: potential risk of subglottic stenosis.

Anesthetic considerations

Patient cooperation may be limited as a consequence of developmental delay. Pulmonary function usually is not severely impaired. Consider side effects of steroids and chemotherapeutic agents used in treatment of malignant transformation and bone marrow transplantation.

Pharmacological implications

Cardiac-depressant drugs should be used with care. Corticosteroid coverage following steroid use.

References