Authors: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mefford HC, Stephens K, Amemiya A, Ledbetter N
CLINICAL CHARACTERISTICS: WAC-related intellectual disability (ID) is typically characterized by variable degrees of global developmental delay and/or intellectual disability. Behavioral abnormalities including anxiety, attention deficit/hyperactivity disorder, and/or autism spectrum disorder are observed in the majority of older children and adults. Most affected infants have significant but nonspecific features at birth such as neonatal hypotonia and feeding problems. Some affected individuals come to medical attention with respiratory or vision problems. Facial features may be mildly dysmorphic, but are nonspecific. To date, 18 individuals have been identified with WAC-related ID.
DIAGNOSIS/TESTING: The diagnosis of WAC-related ID is established in a proband by identification of a heterozygous pathogenic variant in WAC on molecular genetic testing.
MANAGEMENT: Treatment of manifestations: Standard treatment of global developmental delay/intellectual disability, behavioral abnormalities, neonatal hypotonia, and feeding problems. Surveillance: Regular dietary evaluation in infancy to ensure optimal nutritional status; routine monitoring of developmental progress and educational needs; assessment for anxiety, attention, and aggressive or self-injurious behavior.
GENETIC COUNSELING: WAC-related ID is inherited in an autosomal dominant manner. With the exception of one family with presumed parental germline mosaicism, all individuals diagnosed to date have the disorder as the result of a de novo pathogenic variant. Once the WAC pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.