Behavioral Phenotypes and Genetic Syndromes
Over the past few decades genetic advances have resulted in increasing understanding of the etiology of intellectual disability (ID) syndromes while detailed phenotypic descriptions of behavior and mental disorders have become possible with validated and reliable assessment tools. Although the concept that certain ID syndromes are associated with a recognizable physical, behavioral, and cognitive “phenotype” is not new, it has gained considerable popularity among psychiatrists and psychologists working with this population. In this chapter, we will review the key aspects of behavioral phenotypes and genetic testing before describing some of the phenotypes associated with specific syndromes. For terms in italics, see “Glossary.”
Alternative version of a specific gene responsible for variations in characteristics such as blood type.
Abnormal number of copies of sections of the DNA on certain chromosomes. It is usually caused by submicroscopic structural rearrangements such as deletions, duplications, or translocations.
Method for analysis of CNVs in a part of DNA based on microarray technology.
Alleles that determine the phenotype seen in a heterozygote.
Addition of a methyl group to DNA that may affect the expression of genes. An epigenetic mechanism.
Process of determining the order of nucleotides containing four bases [(G) guanine, (A) adenine, (T) thymine, and (C) cytosine] in a segment of DNA.
Any factor which influences the phenotype but is not part of the genotype.
Technique developed in the early 1980s to detect the presence or absence of specific DNA sequences on chromosomes.
A map of positions of known genes on the chromosomes.
A natural process where certain genes are expressed or silenced (without alteration of their genetic code) depending on whether they are inherited from the mother or the father. Genetic conditions associated with imprinting defects include Angelman and Prader–Willi syndromes.
Examination of the genome for common variants in different individuals usually focusing on associations between SNPs and major diseases.
Photographed chromosomes arranged by size.
The tendency of genes close together on the same chromosome to be inherited together.
The presence of certain combinations of alleles of closely linked genes on the same chromosome more often than it would be expected by chance.
This occurs when mutations in genes at different chromosomal loci cause the same phenotype.
Presence of two or more populations of cells with different genotypes in one organism. It results from a mutation during development affecting only a subset of the organism’s cells.
Technique for copying strands of DNA in order to increase the available amount for study and analysis.
A gene that is masked in the presence of a dominant allele.
Lab technique by which the nucleotide sequence for a specific segment of DNA is determined.
A variant DNA sequence in which the base of a single nucleotide has been replaced by another (e.g., cytosine replaced by thymine).
A gene that protects a cell from transforming to a cancerous cell. When this gene is mutated and loses or reduces its function, the cell can progress to cancer, usually in combination with other factors.
Inheritance of both copies of a chromosome from one parent.
Trait that is caused by mutation of a gene located on the X chromosome.
A disorder due to a mutation in a gene on the X chromosome that causes the disease traits to be expressed in all males or females who are homozygous for the gene mutation.
- Antar, L. N., Afroz, R., Dictenberg, J. B., Carroll, R. C., & Bassell, G. J. (2004). Metabotropic glutamate receptor activation regulates fragile X mental retardation protein and Fmr1 mRNA localization differentially in dendrites and at synapses. The Journal of Neuroscience, 24(11), 2648–2655.PubMedCrossRefGoogle Scholar
- Boer, H., Holland, A., Whittington, J., et al. 2002. Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet, 359, 135–136.Google Scholar
- Burnside, R. D., Pasion, R., Mikhail, F. M., Carroll, A. J., Robin, N. H., Youngs, E. L., et al. (2011). Microdeletion/microduplication of proximal 15q11.2 between BP1 and BP2: A susceptibility region for neurological dysfunction including developmental and language delay. Human Genetics, 130, 517–528.PubMedCrossRefGoogle Scholar
- De Waele, K., Ishkanian, S. L., Bogarin, R., Miranda, C. A., Ghatei, M. A., Bloom, S. T., et al. (2008). Long acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader-Willi syndrome. European Journal of Endocrinology, 159, 381–388.PubMedCrossRefGoogle Scholar
- DYSCERNE—Angelman Syndrome Guideline Development Group (2010) Management of Angelman syndrome: A clinical guideline. Retrieved from http://www.dyscerne.org/dysc/digitalAssets/0/263_Angelman_Guidelines.pdf
- Hatton, D. D., Sideris, J., Skinner, M., Mankowski, J., Bailey, D. B., Roberts, J., et al. (2006). Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP. American Journal of Medical Genetics, 140, 1804–1813.Google Scholar
- Jones, A. C., Shyamsundar, M. M., Thomas, M. W., Maynard, J., Idziaszczyk, S., Tomkins, R., et al. (1999). Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. American Journal of Human Genetics, 64(5), 1305–1315.PubMedCrossRefGoogle Scholar
- Karayiorgou, M., Morris, M. A., Morrow, B., Shprintzen, R. J., Goldberg, R., Borrow, J., et al. (1995). Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proceedings of the National Academy of Sciences of the United States of America, 92, 7612–7616.PubMedCrossRefGoogle Scholar
- Morris, C. A. (1999 Apr 9). Williams syndrome. [Updated 2006 Apr 21]. In R. A. Pagon, T. D. Bird, C. R. Dolan, et al. (Eds.), GeneReviews™ [Internet]. Seattle, WA: University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1249/
- Northrup, H., Koenig, M. K., & Au, K. S. (1999). Tuberous sclerosis complex. [Updated 2011 Nov 23]. In R. A. Pagon, T. D. Bird, C. R. Dolan, et al. (Eds.), GeneReviews™ [Internet]. Seattle, WA: University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1220/
- Nyhan, W. L., O’Neill, J. P., Jinnah, H. A., Harris, J. C. (2010). Lesch-Nyhan syndrome. [Updated 2010 Jun 10]. In R. A. Pagon, T. D. Bird, C. R. Dolan, et al. (Eds.), GeneReviews™. Seattle, WA: University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1149/
- O’Brien, G., & Bevan, R. (2011). Recent advances in behavioural phenotypes as they affect adults. Advances in Mental Health and Intellectual Disabilities, 5(4), 5–14.Google Scholar
- Saul, R. A., Tarleton, J. C. (1998). FMR1-related disorders. [Updated 2012 Apr 26]. In R. A. Pagon, T. D. Bird, C. R. Dolan, et al. (Eds.), GeneReviews™ [Internet]. Seattle, WA: University of Washington, Seattle. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK1384/
- Shinawi, M., Liu, P., Kang, S. H., Shen, J., Belmont, J. W., Scott, D. A., et al. (2010). Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. Journal of Medical Genetics, 47(5), 332–341.PubMedCrossRefGoogle Scholar
- Stancliffe, R. J., Lakin, K. C., Larson, S. A., Engler, J., Taub, S., Fortune, J., et al. (2012). Demographic characteristics, health conditions, and residential service use in adults with Down syndrome in 25 U.S. states. Intellectual and Developmental Disabilities, 50(2), 92–108.PubMedCrossRefGoogle Scholar
- Wulffaert, J., Berckelaer-Onnes, I., Kroonenberg, P., Scholte, E., Bhuiyan, Z., & Hennekam, R. (2009). Simultaneous analysis of the behavioural phenotype, physical factors, and parenting stress in people with Cornelia de Lange syndrome. Journal of Intellectual Disability Research, 53, 604–619.PubMedCrossRefGoogle Scholar