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Understanding Chromosome Disorders and their Implications for Special Educators

Linda Gilmore

Queensland University of Technology Brisbane, Australia

Address for correspondence

Dr Linda Gilmore Faculty of Education Queensland University of Technology Victoria Park Road Kelvin Grove QLD 4059 Australia

Phone +61 7 3138 9617 Fax +61 7 3138 3987 Email: [email protected]

Running head: CHROMOSOME DISORDERS 2

Abstract

More children are now being diagnosed with chromosome abnormalities. Some chromosome disorder syndromes are relatively well known, while others are so rare that there is only limited evidence about their likely impact on learning and development. For educators, a basic level of knowledge about chromosome abnormalities is important for understanding the literature and communicating with families and professionals. This paper describes chromosomes, and the numerical and structural anomalies that can occur, usually spontaneously during early cell division.

Distinctive features of various chromosome syndromes are summarised before a discussion of the rare chromosome disorders that are labelled, not with a syndrome name, but simply by a description of the chromosome number, size and shape.

Because of the potential within-group variability that characterises syndromes, and the scarcity of literature about the rarer chromosome disorders, expectations for learning and development of individual students need to be based on the range of possible outcomes that may be achievable.

Keywords: chromosomes, chromosome disorders, chromosome abnormalities, rare chromosome disorders, developmental outcomes Running head: CHROMOSOME DISORDERS 3

Introduction

Many children who attend special education settings are identified as having

chromosome disorders that account for their disabilities. Some chromosome

disorders, such as , are relatively well known while others are much less familiar or virtually unknown. For the majority of educators who have little or no training in biology, understanding the complexities of genetics and chromosome disorders can be both daunting and challenging. Yet a basic level of knowledge about the underlying cause of a child’s disability is important if teachers are to provide the

necessary support for learning and development. This paper begins by presenting

basic information about chromosomes and chromosome abnormalities. The

developmental consequences of the more common chromosome disorder syndromes are then summarised before the focus turns to the rare, and at times apparently unique, chromosome disorders that are now being diagnosed with increasing frequency.

Chromosomes Abnormalities

In every cell of the human body (except for the egg or sperm cells and red

blood cells) there are 23 pairs of chromosomes. These are numbered from 1 to 22,

largest to smallest, with the 23rd pair consisting of the sex chromosomes: for females,

two X chromosomes; for males, one X and one (Turnpenny & Ellard,

2005). The descriptors 46,XX or 46,XY are used, respectively, to refer to a female or

male with the normal complement of chromosomes.

Deviations from this normal complement occur in 0.5 to 1% of live births and

more than half of all (Carey, 2003; Gardner & Sutherland, 2004;

Haydon, 2008). Varying amounts of chromosome material may be lost, duplicated or

rearranged in some way. These anomalies can be inherited from a parent or, more

commonly, occur spontaneously when chromosomes fail to separate properly during Running head: CHROMOSOME DISORDERS 4

early cell division. The factors that cause these spontaneous errors are largely

unknown, but are presumed to be “accidental”. Older mothers are more likely to

conceive a child with a chromosome disorder. Maternal age has consistently been

associated with Down syndrome and other chromosome disorders (Hook, 1981;

Morris, Wald, & Mutton, 2003) with the risk rising dramatically with advanced

reproductive age.

A number of terms are used when describing chromosome abnormalities.

These include the letters p and q which refer, respectively, to the shorter and longer

arms of the chromosome. These two arms are joined in the middle by a centromere,

and the tips of the chromosome are known as telomeres. As shown in Figure 1, a

numbering system is used to identify precise regions, bands and sub-bands along the

chromosome (Carey, 2003).

INSERT FIGURE 1 ABOUT HERE

Chromosome deletions result from breakages and subsequent loss of material,

either at the end of a chromosome (terminal ) or at some point within the

chromosome (interstitial deletion). In the example shown in Figure 1, brackets have

been inserted to illustrate the region that has been lost for a person with deletion

16q11.2q13. Breakages may also result in extra chromosome material (i.e., a third

copy of a segment) being present, an anomaly that is referred to as a duplication or

partial . The most common chromosome disorder, Down syndrome, usually involves a third complete copy of (i.e., Trisomy 21).

As well as deletions and duplications, chromosome material can potentially be

rearranged in various ways. Broken segments of two or more chromosomes may

exchange places. Known as translocations, such rearrangements may have little

impact on health and development provided all the chromosome material is still Running head: CHROMOSOME DISORDERS 5 present in each cell and the translocation is thus balanced. However, there are likely to be problems with reproduction, and in future generations there is a substantial risk of unbalanced rearrangements that result in missing or additional chromosome material (i.e., deletions or duplications). Other chromosome anomalies include inversions, which involve two breakages followed by reconnection of the intervening segment in reverse order, and rings that are formed when both chromosome tips break off and the two sticky ends join to form a circle.

Chromosome Disorder Syndromes

Some of the more common chromosome abnormalities have been classified as syndromes. The best known is Down syndrome which is usually caused by an extra chromosome 21 in every cell of the body. Cases have been reported in which only a proportion of cells have the additional chromosome (known as Trisomy 21) and in these cases, developmental outcomes depend on the type and number of cells that are affected (de A. Moreira, San Juan, Pereira, & de Souza, 2000; Fishler, Koch,

& Donnell, 1976). A small percentage of individuals with Down syndrome have a section of chromosome 21 attached to another chromosome, most commonly chromosome 14.

Other trisomy syndromes include Patau (Trisomy 13) and

(Trisomy 18). In the relatively small proportion of 13 and 18 that result in live births, developmental consequences are more severe than those associated with

Down syndrome, and few children survive to adulthood (Baty, Jorde, Blackburn &

Carey, 1994; Crider, Olney, & Cragan, 2008). The only other trisomy syndromes that are survivable involve the sex chromosomes, X or Y. An additional copy of the leads to (47,XXY) in males, or XXX syndrome in females, while an additional Y chromosome produces XYY syndrome (Leggett, Running head: CHROMOSOME DISORDERS 6

Jacobs, Nation, Scerif, & Bishop, 2010). Further additions of the sex chromosomes are possible – for instance, XXXX ( X) or XXXXX (). There

is one survivable condition that involves a complete missing chromosome. Turner

syndrome results from the absence of one X chromosome, producing the

45,X in affected females (Powell & Schulte, 2011). In some cases, only part of the

second X chromosome is missing.

Apart from these syndromes which involve changes in the total number of

chromosomes, there are many others that result from structural changes to one or

more chromosomes. These include Wolf-Hirschhorn, Cri du Chat, Williams, Smith-

Magenis, and Velocardiofacial syndromes which involve deletions on chromosomes

4p, 5p, 7q, 17p and 22q, respectively. Deletions on the long arm of inherited from the father produce Prader-Willi syndrome while the same deletion on the maternally derived chromosome produces . Other less familiar chromosome deletion syndromes include Jacobsen (deletion on 11q) and

Miller-Dieker, which results from a deletion on 17p, but at a different breakpoint from

Smith-Magenis syndrome.

There is considerable variability in the developmental consequences associated with these chromosome disorder syndromes. Most involve some degree of but the level of impairment is very variable, both within and across syndromes. More severe levels of intellectual impairment are associated with

Angelman, Smith Magenis, and . Intelligence is usually within the average range for girls and women with , although learning difficulties, especially in mathematics, are common (Mazzocco & Hanich, 2010;

Rovet, 2004). Some individuals with Velocardiofacial syndrome may have intellectual ability within the average to low average range, while others affected by Running head: CHROMOSOME DISORDERS 7

the syndrome will have mild to moderate intellectual impairment (Furniss, Biswas,

Gumber, & Singh, 2011).

Profiles of cognitive strengths and weaknesses are evident too. For instance,

children with tend to have relative strengths in language and

auditory memory, but weaknesses in visuospatial skills (Mervis & John, 2010).

Similarly, those with Velocardiofacial (Furniss et al., 2011) and Turner (Hong, Kent,

& Scaletta Kesler, 2009) syndromes often perform less well with visuospatial and nonverbal tasks than on tasks requiring auditory/verbal ability. By contrast, the cognitive profile for children with Down syndrome shows relative strengths in visuospatial skills and weaknesses in verbal abilities (Fidler, Hepburn, & Rogers,

2006).

In addition to cognitive impairments, there may be problems in areas such as

communication, attention, executive functioning, and behaviour. For some

syndromes, there are distinctive phenotypic features including hyperphgagia

(compulsive eating and food obsessions) in Prader Willi (Whittington & Holland,

2010), and self-injurious behaviour in Smith Magenis (Dykens & Smith, 1998) and

Cri du Chat (Collins & Cornish, 2002) syndromes. Relative strengths are sometimes

displayed, such the desire for social interaction in Angelman (Oliver et al., 2007),

Williams (Jones et al., 2000) and Down (Fidler et al., 2006) syndromes, although

over-friendliness and hypersociability can create social vulnerability.

Mental health problems are also relatively common in chromosome disorder

syndromes. These include attention deficit disorder, phobias and anxiety associated

with Williams syndrome (Stinton, Elison, & Howlin, 2010); repetitive, ritualistic behaviours in Prader-Willi syndrome (Greaves, Prince, Evans, & Charman, 2006); and high rates of anxiety and depression, attention deficit, and psychotic disorders Running head: CHROMOSOME DISORDERS 8

such as schizophrenia in Velocardiofacial syndrome (Gothelf, Frish, Michaelovsky,

Weizman, & Shprintzen, 2009).

Rare Chromosome Disorders

There is also a wide array of less common or less distinctive chromosome disorders that occur in live births but which are not identified by a syndrome name.

Rather, they are labelled using a description of the chromosome number, size and shape, called the karyotype. Such labels create difficulties for families who need to communicate their child’s disorder to others, and potential confusion for education systems and service providers who are required to categorise the disability.

Diagnoses such as “Deletion 4q33qter with Duplication 10p13pter” are not easily understood! (In this example, the affected individual has both a deletion of the end segment of the long arm of , from 4q33 to the end (ter = terminal) as well as a duplication of the end segment of the short arm (p) of chromosome 10.)

Furthermore, many chromosome disorders are often so rare that there are currently few or no other cases with the same anomaly reported in the literature or recorded on clinical databases anywhere in the world, making prognosis difficult and approaches to intervention uncertain (Gilmore & Campbell, 2006).

Although the overwhelming majority of rare chromosome disorders are known only by their (description of chromosomes), a few have been given syndrome names in recent years. These include Koolen-DeVries syndrome which

results from a microdeletion of 17q21.31 and Kleefstra syndrome that involves a

deletion at 9q34.3. In Pallister-Killian syndrome, some cells of the body have a small

additional chromosome comprising two copies of the p arm of chromosome 12 (i.e.,

mosaic tetrasomy 12p). Another unusual anomaly is seen in individuals with Emanuel

syndrome who have an extra chromosome made up of the top (p arm) and middle Running head: CHROMOSOME DISORDERS 9

(centromere) of plus the bottom (q arm) of . (For

information about these and a wide range of other rare chromosome disorders see

www.rarechromo.org.)

Across all available literature about rare chromosome disorders, characteristics

such as growth retardation, developmental delay, intellectual disability, delayed or

impaired speech, behaviour problems and sensory deficits are frequently documented.

For the overwhelming majority of the vast number of reported chromosome abnormalities that are survivable, however, research has involved only small samples or individual case reports and, as mentioned above, for some anomalies there is a total absence of literature. Even when published reports are available, they are likely to be biased towards individuals with more severe developmental outcomes, and are thus not a portrayal of the range of outcomes that are potentially achievable (see Gilmore,

2009).

Indeed, a close scrutiny of existing literature about rare chromosome disorders reveals that, amidst findings of deficits and adverse developmental outcomes, there are also reports of individuals who are developing quite typically, at least in some domains. There are, for instance, numerous cases of individuals with chromosome deletions or duplications who have intellectual ability within the average range (e.g.,

Bartels, Pütz, Reintjes, Netzer, & Shoukier, 2013; Chen, Cherry, Hahn & Enns, 2004;

Cobb et al., 2010; Gilmore, Cuskelly, Jobling & Smith, 2001; Zarate, Kogan,

Schorry, Smolarek, & Hopkin, 2007). Thus, it is clear that adverse developmental outcomes are not necessarily inevitable.

Implications for Special Educators

For educators in both mainstream and special school settings, a basic

knowledge of genetics and chromosomes is important for understanding relevant Running head: CHROMOSOME DISORDERS 10

literature about a student’s disorder. This knowledge also enables educators to

communicate more effectively with families and professionals. In particular,

knowledge about the types of chromosome anomalies that can occur is valuable for

understanding rare disorders whose diagnosis involves a string of letters and numbers

that are otherwise incomprehensible.

Research about the phenotypic cognitive and behavioural profiles of the more common chromosome disorders enables educators to develop interventions that target a student’s likely strengths and weaknesses, and to anticipate future potential areas of

difficulty. There is, however, an important caution to keep in mind when reading the literature. Descriptions of particular disabilities are generally derived from observations and assessments of a group of individuals with that specific disorder, and conclusions about developmental and learning characteristics (i.e., the behavioural phenotype) are based on these group data. Unfortunately, it is not always apparent that some individuals with a particular disorder may do considerably better than the group, while others may not develop as well. Keeping in mind this caution is important, because to some extent adult expectations are likely to be influenced by the literature about a specific disability. Each child will have individual areas of strength and weakness as well as many personal characteristics that are unrelated to their disorder but which may be overlooked if a student is defined solely by his or her disability label. An evaluation of the literature about a child’s disability is valuable to identify particular features that are likely to be present, so long as there is also a recognition that a specific student may differ in many ways from others with the same diagnosis.

In relation to the rarer chromosome abnormalities, the extremely limited literature means that educators have few available resources for guiding their Running head: CHROMOSOME DISORDERS 11 approaches to teaching students with these disorders. Within education systems that are accustomed to categorising children according to their learning needs and perceived potential, decisions are inevitably hampered by the lack of a recognisable disability diagnosis. Even in instances where single or multiple case reports are available in the published literature, these are unlikely to be representative of others with the same, or similar, chromosome abnormalities. Thus, for these students, expectations need to be cautiously optimistic, rather than constrained by negative case reports in the literature, and decisions about educational placement and intervention need to be based on a combination of evidence that includes comprehensive psycho- educational assessment.

One resource that is likely to be of considerable value to educators is the

Unique Rare Chromosome Disorder Support Group (www.rarechromo.org) which has established a rich database containing the developmental histories of many thousands of individuals with a rare chromosome disorder. The Unique website offers free information leaflets on a wide range of rare chromosome disorders, as well as general information about chromosome abnormalities and their consequences for development and learning. The leaflets, which are derived from a merging of the scientific literature and Unique’s own database, are rigorously produced, medically verified, and regularly updated.

In summary, chromosome disorders are relatively common, and an increasing number of individuals are being diagnosed with rare chromosome disorders that are not identified by a syndrome name. Educators will benefit from a basic level of understanding of genetics that maximises their ability to understand relevant literature and to communicate more effectively with families and professionals. Because of the potential within-group variability that characterises chromosome disorder syndromes, Running head: CHROMOSOME DISORDERS 12 and the scarcity of literature about the rarer chromosome disorders, expectations about future learning and development need to be tentative, taking into consideration the range of possible outcomes that may be achievable for a student with a chromosome disorder, as well as the unique individual, family and contextual characteristics that are also likely to influence development and learning. Running head: CHROMOSOME DISORDERS 13

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Figure 1 Chromosome 16 with the region 16q11.2q13 bracketed