DYRK1A-Related Intellectual Disability Syndrome. 21q22.13q22.2 microdeletion syndrome.
Incidence
DYRK1A-related intellectual disability syndrome is inherited in an autosomal dominant manner. Prevalence: <1 / 1 000 000. To date all affected individuals represent simplex cases (i.e., a single occurrence in a family) resulting from a de novo DYRK1A pathogenic variant. DYRK1A-related intellectual disability syndrome accounted for 0.1%-0.5% of individuals with intellectual disability and/or autism.
Clinical Characteristics
DYRK1A-related intellectual disability 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, a few individuals with mild intellectual disability have been reported. About half of affected individuals develop epilepsy including atonic attacks, absences, and generalized myoclonic seizures. About half of affected individuals develop scoliosis, kyphosis, and/or pectus excavatum. About one third have short stature. Rarely, endocrine problems and dental, ophthalmologic, and/or cardiac anomalies are reported.
Precipitants
None.
Provocation Tests
None.
Diagnostic Procedures
The diagnosis of DYRK1A-related intellectual disability syndrome is established in a proband by identification of a heterozygous pathogenic variant in DYRK1A. No formal clinical criteria exist for diagnosis of DYRK1A-related intellectual disability syndrome. DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion.