DYRK1A Syndrome

Clinical characteristics: DYRK1A syndrome is characterized by intellectual disability including impaired speech development, autism spectrum disorder including anxious and/or stereotypic behavior problems, and microcephaly. Affected individuals often have a clinically recognizable phenotype including a typical facial gestalt, feeding problems, seizures, hypertonia, gait disturbances, and foot anomalies. The majority of affected individuals function in the moderate-to-severe range of intellectual disability; however, individuals with mild intellectual disability have also been reported. Other medical concerns relate to febrile seizures in infancy; the development of epilepsy with seizures of the atonic, absence, and generalized myoclonic types; short stature; and gastrointestinal problems. Ophthalmologic, urogenital, cardiac, and/or dental anomalies have been reported.

Diagnosis/testing: The diagnosis of DYRK1A syndrome is established in a proband with suggestive findings and a heterozygous pathogenic variant in DYRK1A identified by molecular genetic testing.

Management: Treatment of manifestations: Educational and therapy programs to address the specific needs identified; routine treatment of epilepsy under the care of a neurologist; standard treatment for orthopedic, dental, cardiac, urogenital, ophthalmologic, constipation, and other medical issues.

Surveillance: Regular monitoring and guidance for educational and behavior problems, growth parameters and nutritional status, and safety of oral intake; regular lifelong follow up as determined by specialists for issues present affecting heart, eyes, and teeth.

Genetic counseling: DYRK1A syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. If the DYRK1A pathogenic variant identified in the proband is not identified in either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism. Once the DYRK1A pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.