What is a KAT6A-related disorder?
KAT6A-related disorder occurs when there is a change or alteration (like a spelling mistake) to the KAT6A gene, meaning the gene loses or alters its usual function. This results in changes to the usual development patterns in the affected individual.
KAT6A is a gene on the short arm (the ‘p’ arm) of chromosome 8. It is within the band 8p11.21. Whilst the exact function of the KAT6A gene is not yet fully understood, it is part of a group of genes known to affect many body functions. The KAT6A gene makes the KAT6A protein, which then helps to control the production of proteins from other genes. The KAT6A protein is involved in unravelling specific parts of the chromosome so that other proteins can be made. It also modifies proteins once they have been made. Because the KAT6A protein is involved in controlling the expression of many other genes, a variation in the KAT6A gene can cause changes in many different parts of the body. We do not yet fully understand all the functions of the KAT6A gene and protein. 3, 5
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Frequently asked questions
Children with KAT6A variations commonly have intellectual disability, hypotonia (low muscle tone), vision difficulties (including strabismus/crossed-eyes), feeding difficulties, reflux, congenital heart defects, and sleep disturbance. Facial features commonly include microcephaly (small head size), a broad nasal tip that becomes more prominent with age and a thin upper lip.2,3 Behavioural problems and autistic features have been noted. 2
Marked speech and language delay is common alongside intellectual disability in individuals with this condition. Some individuals remain non-verbal into adulthood. 2
It is currently unclear when individuals with a KAT6A gene mutation begin speaking. From the research conducted on the development of these individuals, it has only been identified that speech development is severely impacted. 1,3,4
It is currently unclear whether there are any definitive characteristics of speech in individuals with a KAT6A gene mutation. However, for many of the cases reported, the speech profile is severe. Some report oromotor dyspraxia and verbal dyspraxia (also called Childhood Apraxia of Speech, CAS) as particularly common, but the specific speech profile of KAT6A has not been clearly described. 2
It is currently unclear how an individual with a KAT6A gene mutation will develop their speech over time. Current reports demonstrate variability in speech and language outcome ranging from some children who have limited or no speech into adulthood (referred to as being ‘non-verbal’ or ‘minimally verbal’), while others do develop functional speech and language despite early significant delays. Sign language and communication aids have been reported as helpful to facilitate communication.2
There is no research on speech and language interventions that are specifically designed for individuals with KAT6A 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.
The specific adolescent and adult profile of KAT6A variations is currently unknown.
There is no current research evidence that reports common speech sound development in those with KAT6A variations.
- Eising, E., Carrion-Castillo, A., Vino, A., Strand, E. A., Jakielski, K. J., Scerri, T. S., Hildebrand, M. S., Webster, R., Ma, A., Mazoyer, B., Francks, C., Bahlo, M., Scheffer, I. E., Morgan, A. T., Shriberg, L. D. & Fisher, S. E. (2018). A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development. Molecular Psychiatry, 20(1).
- Kennedy, J., Goudie, D., Blair, E., Chandler, K., Joss, S., McKay, V., Green, A., Armstrong, R., Lees, M., Kamien, B., Hopper, B., Tan, T.Y., Yap, P., Stark, Z., Okamoto, N., Miyake, N., Matsumoto, N., Macnamara, E., Murphy, J.L., McCormick, E., Hakonarson, H., Falk, M.J., Li, D., Blackburn, P., Klee, E., Babovic-Vuksanovic, D., Schelley, S., Hudgins, L., Kant, S., Isidor, B., Cogne, B., Bradbury, K., Williams, M., Patel, C., Heussler, H., Duff-Farrier, C., Lakeman, P., Scurr, I., Kini, U., Elting, M., Rejinders, M., Schuurs-Hoeijmakers, J., Wafik, M., Blomhoff, A., Ruivenkamp, C.A.L., Nibbeling, E., Dingemans, A.J.M., Douine, E.D., Nelson, S.F., DDD Study, Arboleda, V.A., Newbury-Ecob, R. (2019). KAT6A Syndrome: genotype–phenotype correlation in 76 patients with pathogenic KAT6A variants. Genetics in Medicine, 21(4), 850-860.
- Millan, F., Cho, M. T., Retterer, K., Monaghan, K. G., Bai, R., Vitazka, P., Everman, D.B., Smith, B., Angle, B., Roberts, V., Immken, L., Nagakura, H., DiFazio, M., Sherr E., Haverfield, E., Friedman, B., Telegraphi, A., Juusola, J., Chung, W.K., & Bale, S. (2016). Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder. American Journal of Medical Genetics – Part A, 170(7), 1791-1798.
- Tham, E., Lindstrand, A., Santani, A., Malmgren, H., Nesbitt, A., Dubbs, H.A., Zackai, E.H., Parker, M.J., Milan, F., Rosenbaum, K., Wilson G.N., Nordgren, A. (2015). Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features. American Journal of Human Genetics, 96, 507–13.
- Voss, A. K., Thomas, T. (2009). MYST family histone acetylytransferases take center stage in stem cells and development. Bioessays, 31, 1050-1061.