SHANK3

What is SHANK3 syndrome?

SHANK3 gene is located on chromosome 22, on the q arm (22q13.3) and encodes a scaffolding protein that regulates synaptic development, function, and plasticity. SHANK3 gene has an important role in the assembly of postsynaptic signalling molecules and consequently affects brain development. SHANK3 syndrome is also referred to as 22q13.3 deletion syndrome or Phelan-McDermid syndrome.1,2SHANK3 syndrome is a neurodevelopmental disorder characterised by hypotonia (low muscle tone), intellectual disability (mild to severe), global developmental delay, and autism. Challenges with attention (e.g., attention deficit hyperactivity disorder, ADHD) and schizophrenia are also noted. Fine and gross motor difficulties are common. 1,2,3,4

 

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

There is much variation in the developmental presentation of children with SHANK3 syndrome. The presence and severity of other associated features (e.g., intellectual disability) may also affect speech development. Based on present research, children with SHANK3 syndrome will take more time to reach developmental speech and language milestones relative to peers, while other children with SHANK3 syndrome are unable to speak verbally. 2,4

There is large variation in speech and language abilities of individuals with SHANK3 syndrome.2,4 SHANK3 syndrome has been associated with Childhood Apraxia of Speech (CAS). CAS is a motor speech disorder affecting production, sequencing, and stress of speech.4

There is considerable variability between individuals with this condition. Currently, there is not enough data to inform exactly how speech develops overtime and when certain milestones can be anticipated. Some individuals do not develop enough verbal speech to rely on this for their daily communication needs. These individuals require augmentative and alternative communication (AAC) systems to communicate, whilst other individuals can rely on verbal speech to communicate.2

The education background of only one individual has been published in the literature so far. This individual attended mainstream school setting.4 However, any individual should be assessed for their needs, and should attend the most appropriate education setting based on their needs, the supports available in different educational settings and of course taking into consideration local educational policies.

At present, speech and language therapies are focused on the individual’s specific speech and language needs. A speech pathology assessment will pinpoint the specific areas for support, taking into consideration the goals for the individual/family. Children who have few spoken words or some words that are unclear, may benefit from augmentative and alternative communication (AAC) options (e.g., sign language, electronic speech generating devices).

For verbal children who have CAS, the Nuffield Dyspraxia Programme version 3 (NDP-3) or the Rapid Syllable Transition Treatment (ReST), are two programs which have been proven to be effective in a randomised controlled trial.5 There are currently a number of other CAS focused therapies undergoing rigorous clinical testing, including Dynamic Tactile Temporal Cueing.6 One treatment that is often used for children who are minimally verbal and who benefit from tactile prompts (prompts to the lips, cheek etc) to help stimulate speech production is Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT). 7,8 Yet to date, none of these therapies have not been specifically trialled with children with neurogenetic conditions. Further to the speech production therapies, children who have delayed language also require early intervention programs targeting early language development.9

For information and support on childhood apraxia of speech: https://www.apraxia-kids.org

References

  1. Ebert, D. H., & Greenberg, M. E. (2013). Activity-dependent neuronal signalling and autism spectrum disorder. Nature, 493(7432), 327-337.
  2. De Rubeis, S., Siper, P. M., Durkin, A., Weissman, J., Muratet, F., Halpern, D., ... & Kolevzon, A. (2018). Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Molecular autism, 9(1), 1-20.
  3. Gauthier, J., Champagne, N., Lafrenière, R. G., Xiong, L., Spiegelman, D., Brustein, E., ... & Gourion, D. (2010). De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. Proceedings of the National Academy of Sciences, 107(17), 7863-7868.
  4. Kaspi, A., Hildebrand, M. S., Jackson, V. E., Braden, R., Van Reyk, O., Howell, T., ... & Morgan, A. T. (2022). Genetic aetiologies for childhood speech disorder: novel pathways co-expressed during brain development. Molecular psychiatry, 1-17.
  5. Murray, E., McCabe, P., & Ballard, K. J. (2015). A randomized controlled trial for children with childhood apraxia of speech comparing rapid syllable transition treatment and the Nuffield Dyspraxia Programme–Third Edition. Journal of Speech, Language, and Hearing Research, 58(3), 669-686.
  6. Strand, E. A. (2020). Dynamic temporal and tactile cueing: A treatment strategy for childhood apraxia of speech. American Journal of Speech-Language Pathology, 29(1), 30-48.
  7. Morgan, A. T., Murray, E., & Liegeois, F. J. (2018). Interventions for childhood apraxia of speech. Cochrane Database of Systematic Reviews, (5).
  8. Namasivayam, A. K., Huynh, A., Granata, F., Law, V., & van Lieshout, P. (2021). PROMPT intervention for children with severe speech motor delay: a randomized control trial. Pediatric research, 89(3), 613-621.
  9. Ebbels, S. H., McCartney, E., Slonims, V., Dockrell, J. E., & Norbury, C. F. (2019). Evidence‐based pathways to intervention for children with language disorders. International journal of language & communication disorders, 54(1), 3-19.

Proudly in partnership with