Encephalopathy

CLINICAL CHARACTERISTICS

encephalopathy (-E) is characterized by moderate-to-severe developmental delay / intellectual disability, structural brain abnormalities, and often infantile hypotonia and seizures. Other less common findings include dystonia, reduced vision, behavior issues, growth delay, gastrointestinal (GI) problems, genitourinary (GU) abnormalities in males, and cutaneous mastocytosis.

DIAGNOSIS/TESTING: The diagnosis of encephalopathy (-E) is established in a proband by identification of a heterozygous pathogenic variant by molecular genetic testing.

MANAGEMENT

Developmental delay / intellectual disability, hypotonia, seizures, poor vision, behavior issues, growth delay, GI problems, GU abnormalities in males, and cutaneous mastocytosis are managed as per standard care. Follow up of the common manifestations at each clinic visit.

GENETIC COUNSELING

-E is inherited in an autosomal dominant manner and is typically caused by a pathogenic variant. If the pathogenic variant identified in the proband is not identified in one of the parents, the risk to sibs is low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.