DYRK1A

What is DYRK1A syndrome?

Dual specificity tyrosine phosphorylation regulated kinase 1 A, DYRK1A, plays a significant role in brain development and regulating cell proliferation, including shaping the brain and monitoring the structure of neuronal components. DYRK1A is a protein kinase found in the ‘Down syndrome region’ of chromosome 21, that is critical for nervous system development.

Variations in the DYRK1A gene cause DYRK1A syndrome; a rare condition with a recognisable but heterogeneous phenotype, including a spectrum from mild to severe intellectual disability (ID), speech and language disorders, epilepsy, microcephaly, delayed growth, autism, feeding difficulties, facial gestalt, and vision defects.

For further information contact:

For further information, do get in touch with the CRE Speech and Language research team at:

Email: geneticsofspeech@mcri.edu.au

Phone: (03) 9936 6334

Frequently asked questions

  • Feeding difficulties: in infancy and early childhood, most children experience feeding difficulties. These feeding difficulties are commonly supported with modified diets, and alternative feeding methods (e.g., tube feeding). Later in childhood, many children have oral aversions and sensitivities to food textures which leads to them eating a limited range of foods.1,2
  • Epilepsy: about one-third of children have epilepsy and take medication to control seizures.1,2
  • Vision: most children also have vision impairment, and many require glasses.1
  • Fine & gross motor delay: seeking support from occupational and physiotherapists for these difficulties.1
  • Surgeries: surgeries in this group are common, including surgeries to address vision impairment, gastrointestinal and urinary tract problems, musculoskeletal issues, and adenoidectomies and tonsillectomies.1
  • Heart: approximately one-quarter of individuals have cardiac defects.
  • Behavioural difficulties: these included diagnoses of autism spectrum disorder, attention deficit hyperactive disorder and anxiety.3 Whilst incidence of autism spectrum disorder is high, social motivation is also high in children with DYRK1A syndrome.
  • Sleep disturbances: for example, difficulty falling and staying asleep and waking early.
  • Intellectual disability: all individuals have intellectual disability, ranging from mild to severe in nature.1
  • Slow growth and microcephaly (small head)1,3,5

The age at which children say their first words is very delayed compared to typically developing children. Most children say their first when they are older than 18 months old (for typically developing children this occurs around 12 months old). Many individuals acquire few if any spoken words (often referred to as ‘minimally verbal’) and rely on other forms of communication (Augmentative and Alternative Communication, AAC).1,2,4

If a child begins speaking most will exhibit features of dysarthria, a neuromotor speech disorder. Some will also have another motor speech disorder too, called Childhood Apraxia of Speech (CAS). These motor speech conditions can occur at the same time in the same person.1

Some individuals learn to use single, spoken words but do not learn to combine words using speech to make sentences.1,2 Most individuals who are minimally verbal or have very unclear speech use augmentative and alternative communication (AAC). A small number of individuals do learn to use speech in conversation and converse with others and be understood but usually have dysarthria and/or CAS.1

There is no research on speech and language interventions that are specifically designed for individuals with DYRK1A gene variations. At present an individualised approach should be taken to assessment and management to ensure therapies are tailored to and optimised for each child.

For minimally verbal individuals, interventions often involve the use of AAC communication aides such as key word signing, Picture Exchange Communication Systems® and communication books and boards that contain pictures the child can point to. Speech generating devices (voice output communication aides) are often used and these enable the individual to communicate using an electronic voice. Speech generating devices, also known as high-tech graphic AAC or high-tech AAC, are recommended in this group, as vision and motor impairments can make use of other AAC, such as sign language, difficult.1

For children with CAS, currently there are several treatments for CAS, such as the Nuffield Dyspraxia Programme version 3 (NDP-3) and the Rapid Syllable Transition Treatment (ReST) which are supported by the highest level of evidence at present.6

Due to the prevalence of intellectual disability, most children attend specialist schools.

In the main speech and language study available to date, there were 12 adolescents and young adults with DYRK1A syndrome. As in childhood, there was a range of speech and language skills. Some individuals were minimally verbal and used AAC, and others could engage in conversation independently.1 Likewise, some participants had mildly impaired expressive and receptive language skills, whilst others had severely impaired receptive and expressive language skills.1

There was not yet been any research into how communication changes across the lifespan in DYRK1A syndrome. However, many individuals have been reported to show growth in their speech and language skills well into adolescence and young adulthood.1

References

  1. Morison, L. D., Braden, R. O., Amor, D. J., Brignell, A., van Bon, B. W., & Morgan, A. T. (2022). Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments. European Journal of Human Genetics, 1-12.
  2. van Bon, B. W., Coe, B. P., de Vries, B. B., & Eichler, E. E. (2015). DYRK1A-related intellectual disability syndrome. GeneReviews.

  3. van Bon, B.W., Coe, B.P., Bernier, R., Green, C., Gerdts, J., Witherspoon, K., Kleefstra, T., Willemsen, M.H., Kumar, R., Bosco, P. and Fichera, M., 2016. Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID. Molecular psychiatry21(1), 126-132.

  4. Earl, R. K., Turner, T. N., Mefford, H. C., Hudac, C. M., Gerdts, J., Eichler, E. E., & Bernier, R. A. (2017). Clinical phenotype of ASD-associated DYRK1A haploinsufficiency. Molecular autism8(1), 1-15.

  5. Courraud, J., Chater-Diehl, E., Durand, B., Vincent, M., del Mar Muniz Moreno, M., Boujelbene, I., ... & Piton, A. (2021). Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder. Genetics in Medicine23(11), 2150-2159.

  6. Morgan, A. T., & Vogel, A. P. (2009). A Cochrane review of treatment for childhood apraxia of speech. European journal of physical and rehabilitation medicine45(1), 103-110.

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