Contiguous Gene Disorders

Key Features

• Williams syndrome

  • Deletes the gene for elastin and other neighboring genes at 7q11.23

  • Duplication of chromosome 7q11.23 results in a syndrome that includes speech delay and features of autistic spectrum disorders

• Smith-Magenis syndrome

  • Associated with microdeletion of 17p11

  • Duplication of 17p11 produces Potocki-Lupski syndrome

• Velocardiofacial syndrome (Deletion 22q11 syndrome)

  • Duplication of the 22q11 region produces a mild and highly variable phenotype that ranges from developmental delays and learning disabilities to functionally normal

  • Also known as DiGeorge syndrome

  • Originally described in newborns with cyanotic congenital heart disease, usually involving

    • Great vessel abnormalities

    • Thymic hypoplasia leading to immunodeficiency

    • Hypocalcemia due to absent parathyroid glands

Clinical Findings

• Williams syndrome

  • Characterized by

    • Short stature

    • Congenital heart disease (supravalvular aortic or pulmonic stenosis)

    • Coarse, elfin-like facies with prominent lips

    • Hypercalcemia or hypercalciuria in infancy

    • Developmental delay

    • Neonatal irritability evolving into an overly friendly personality

  • Natural history includes

    • Progression of cardiac disease

    • Predisposition to hypertension and spinal osteoarthritis in adults

  • Mild to moderate intellectual deficits

• Smith-Magenis syndrome

  • Characterized by

    • Prominent forehead

    • Deep-set eyes

    • Cupid-shaped upper lip

    • Self-mutilating behavior

    • Sleep disturbance

    • Intellectual disabilities

  • Some patients also have seizure disorders, hearing loss, thyroid disease, and immunological and lipid abnormalities

  • Potocki-Lupski syndrome is characterized by

    • Growth failure

    • Variable levels of cognitive deficiencies

    • Autistic features

    • Structural abnormalities of the heart (occasionally)

• Velocardiofacial syndrome (Deletion 22q11 syndrome)

  • Characteristics include

    • Mild microcephaly

    • Palatal clefting or incompetence

    • Speech and language delays

    • Congenital heart disease (great vessel abnormalities, tetralogy of Fallot, and a variety of other abnormalities)

  • Some affected individuals are predisposed to psychosis

Diagnosis

• Suspected on the basis of an abnormal phenotype

• Confirmed via microarray

Treatment

• Williams syndrome

  • Calcium restriction may be necessary in early childhood to prevent nephrocalcinosis

• Smith-Magenis syndrome

• Velocardiofacial syndrome (Deletion 22q11 syndrome)