DYRK1A syndrome is a rare genetic disorder that impacts neurodevelopment. It is caused by a variation on the DYRK1A gene, which has a significant role in brain development. The condition is characterized by a range of developmental and physical traits, which become apparent at a young age. Understanding this syndrome begins with its genetic origins and how those changes affect an individual’s growth and function.
The Genetic Basis of DYRK1A Syndrome
DYRK1A syndrome originates from the DYRK1A gene on chromosome 21. This gene provides instructions for making a protein kinase, an enzyme active in the brain. This kinase helps regulate other proteins and directs processes like the growth and specialization of neurons, supporting early brain development.
The syndrome occurs when one of the two copies of the DYRK1A gene is altered. This can be due to a pathogenic variant, like a mutation, or a larger deletion of the chromosome segment that includes the gene. This is known as haploinsufficiency, where one functional copy of the gene is not enough to support typical brain development.
The genetic change is almost always spontaneous, or de novo. This means the alteration occurred randomly in an egg or sperm cell or during early fetal development. Because it is not inherited, genetic testing of parents shows they do not carry the same gene variant found in their child.
Prevalence and Diagnosis
DYRK1A syndrome is a rare condition, with a prevalence estimated at less than one in a million people. However, it accounts for approximately 0.1% to 0.5% of individuals with an intellectual disability or autism. This suggests that while rare in the general population, it is a more frequent cause within specific neurodevelopmental diagnoses. As of 2022, around 600 families were connected with an international support association, and by 2024, one medical clinic had identified 238 people with the syndrome.
The number of diagnosed individuals is increasing due to advances in genetic testing. In the past, many with the syndrome likely remained undiagnosed or misdiagnosed. The accessibility of comprehensive genetic tests, like chromosomal microarray analysis and whole exome sequencing, has improved identification of the genetic cause of a child’s developmental delays. These technologies can detect both gene deletions and smaller sequence variants.
A definitive diagnosis is established through molecular genetic testing that identifies a pathogenic variant in the DYRK1A gene. While physical features or developmental patterns may lead a clinician to suspect the syndrome, only genetic testing can confirm it. The increased use of this testing is expected to reveal that the condition is more common than once believed.
Common Characteristics and Symptoms
Individuals with DYRK1A syndrome often share a combination of physical, developmental, and behavioral characteristics. One of the most common physical traits is microcephaly, or a smaller than average head size. Some have a recognizable facial appearance, which can include deep-set eyes, prominent ears, a short nose with a broad tip, and a small chin. Feeding difficulties are also frequent, sometimes starting in the neonatal period and potentially requiring tube feeding.
Developmentally, the syndrome is characterized by global developmental delay. This includes delays in motor skills, though most children learn to walk, sometimes with an unsteady gait. Speech and language development is significantly impaired, with receptive language (understanding) often stronger than expressive language (speaking). Most individuals function in the moderate-to-severe range of intellectual disability.
Behavioral characteristics are prominent, with a high overlap with autism spectrum disorder (ASD). Other common behaviors include anxiety, hyperactivity, sleep disturbances, and stereotypic or repetitive movements. Febrile seizures during infancy are common, and some individuals may later develop epilepsy with various seizure types.
Inheritance and Recurrence Risk
Since most cases are caused by de novo genetic variants, the risk of parents having a second child with the syndrome is very low, estimated at approximately 1%. This small chance is due to a rare possibility called parental germline mosaicism. This occurs when a fraction of a parent’s egg or sperm cells contains the genetic variant even though it is not present in their blood cells.
While the condition is rarely inherited from an unaffected parent, an individual with DYRK1A syndrome has a different risk of passing it on. As an autosomal dominant disorder, an affected person has a 50% chance of passing the pathogenic DYRK1A variant to each of their children.