BRPF1

What is BRPF1-related disorder?

Haploinsufficiency of BRPF1 can cause BRPF1-related disorder, also known as BRPF1-associated intellectual developmental disorder with dysmorphic facies and ptosis.1,2Most reported individuals with BRPF1-related disorder have vision impairment and intellectual disability (mild to moderate), although some individuals with BRPF1-related disorder do not have intellectual disability. 1,2,3 A smaller number of individuals have epilepsy (approximately 1 in 5 individuals). Some individuals have dysmorphic facial features, infant feeding impairment, gross motor delay, hypotonia (low muscle tone), and skeletal abnormalities. A small number of individuals have autism and/or attention deficit hyperactive disorder.1,2,3 BRPF1 encodes for bromodomain and PHD finger-containing protein 1, a multivalent chromatin regulator with three histone-binding domains and one non-specific DNA-binding module. BRPF1 also has several motifs that interacts with and activates three lysine acetyltransferases, also known as KAT6A, KAT6B and KAT7.

 

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 BRPF1-related disorder. The presence and severity of other associated features (e.g., intellectual disability) may also affect speech development. Based on present research, children with BRPF1-related disorder will take more time to reach developmental speech and language milestones relative to peers.1,2,3

There is large variation in speech and language development of individuals with BRPF1-related disorder.1,2 One speech condition that has been linked to BRPF1-related disorder is Childhood Apraxia of Speech (CAS). 3 CAS is a motor speech disorder affecting production, sequencing, and stress of speech. Another feature of speech reported in BRPF1-related disorder is inconsistent phonological delay and disorder.3

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. 3  Adults in the literature engage in paid employment and work independently, using speech to engage in these activities of daily living.1,2

Of the individuals reported to date in the scientific literature, some individuals attend mainstream school with support, and others attend specialist school settings.1,2,3 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.4 There are currently a number of other CAS focused therapies undergoing rigorous clinical testing, including Dynamic Tactile Temporal Cueing.5 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). 6,7 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.8

Further information and support

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

Email our team at angela.morgan@mcri.edu.au or geneticsofspeech@mcri.edu.au to learn more about our current research with individuals with BRPF1-related disorder.

References

  1. Mattioli, F., Schaefer, E., Magee, A., Mark, P., Mancini, G. M., Dieterich, K., ... & Piton, A. (2017). Mutations in histone acetylase modifier BRPF1 cause an autosomal-dominant form of intellectual disability with associated ptosis. The American Journal of Human Genetics, 100(1), 105-116.
  2. Yan, K., Rousseau, J., Littlejohn, R. O., Kiss, C., Lehman, A., Rosenfeld, J. A., ... & Yang, X. J. (2017). Mutations in the chromatin regulator gene BRPF1 cause syndromic intellectual disability and deficient histone acetylation. The American Journal of Human Genetics, 100(1), 91-104.
  3. 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.
  4. 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.
  5. 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.
  6. Morgan, A. T., Murray, E., & Liegeois, F. J. (2018). Interventions for childhood apraxia of speech. Cochrane Database of Systematic Reviews, (5).
  7. 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.
  8. 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.

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