The SAGE Handbook of Developmental Disorders

Patricia Howlin, Tony Charman, Mohammad Ghaziuddin, Patricia Howlin, Tony Charman, Mohammad Ghaziuddin

• Publisher: SAGE Publications Ltd
• Year: 2011
• ISBN:
  9781473971219
• Edition: 1
• Topic: Psychology
• Subtopic: Clinical Psychology
• Index: Psychology

Over the last four decades, breakthroughs in genetic knowledge, together with the emergence of disciplines devoted to the scientific study of developmental disorders have resulted in much greater awareness of the many different behavioural and genetic phenotypes involved. It is now evident that not only do different disorders have different causes and different manifestations, but different neurological and biochemical bases, different responses to intervention, and different life courses.

Reflecting the enormous changes that have taken place in our knowledge and understanding of developmental disorders, this groundbreaking international volume brings this vast and complex field together for the first time. The Editors have collected together the world?s leading academic scholars and clinicians, to explore how current research across a range of different disciplines can inform clinical practice and help to improve the lives of individuals and their families.

PART 1

Overview

Introduction

Profound changes have occurred in the science and practice of intellectual disability over the past two decades. Apart from the change in terminology from ‘mental retardation’ to ‘intellectual disability’ (Schalock et al., 2007), progress in basic science and clinical practice has shifted the landscape—motivating us to commission leading scholars worldwide to contribute to this volume in order to capture the current state of knowledge and point to new areas of enquiry in the decades ahead.

GENETICS

The last decade has seen a revolution in our knowledge about the genetic basis of intellectual and neurodevelopmental disorders. From the discovery in the late 1950s that trisomy of chromosome 21 was the cause of Down syndrome (Fidler & Daunhauer, Chapter 1), through the knowledge that fragile X syndrome is nearly always caused by expansions of a CGG repeat in the 5′ untranslated region (5′UTR) of the fragile X mental retardation 1 (FMR1) gene (Hagerman, Turk, Schneider & Hagerman, Chapter 3), to the discovery in 1999 that mutations in the X-linked gene for the methyl CpG binding protein (MECP2) were the cause of Rett syndrome (Kerr, Chapter 8), it is now understood that most neurodevelopmental conditions have a genetic basis. However, despite much progress, the underlying genetic basis of other disorders, such as developmental language disorder (Norbury, Chapter 16) and autism spectrum disorders (Lord, Kim & DiMartino, Chapter 14) has remained more elusive. In other cases, genetic subtyping has led to important discoveries, for example, the realization that Prader–Willi syndrome had two different genetic causes: deletion involving the PWSCR of chromosome 15 of paternal origin or the inheritance of two maternally derived, but no paternally derived, chromosome 15s—referred to as maternal uniparental disomy (mUPD) (Whittington & Holland, Chapter 6). This has also led to important clinical observations, with the latter mUPD subtype but not the deletion subtype being highly associated with adult psychosis.

BASIC SCIENCE IMPROVEMENTS

Improvements in perinatal and post-traumatic medicine mean that intellectual disability and other medical sequelae are found in increasing numbers of individuals who are born very preterm (Wolke, Chapter 25) or who have suffered traumatic brain injury (Mandalis, Muscara & Anderson, Chapter 23). Other neurodevelopmental disorders result from different environmental factors such the fetal alcohol spectrum disorders (O’Malley, Chapter 24) and extreme environmental deprivation (Rutter & Azis-Clauson, Chapter 26). In both the latter examples, longitudinal studies have begun to tease out the organic effects of such insults, for example, microcephaly from the post-insult environmental circumstances that may provide protection.

NEUROPSYCHOLOGY

Other important breakthroughs have come from detailed neuropsychological study of profiles on different sets of cognitive skills, despite the presence of low IQ. For example, in individuals with Williams syndrome there is a relative weakness in visuospatial construction (assessed by the pattern construction subtest) and relative strengths in auditory short-term memory and language, even in low-functioning individuals (Plesa Skwerer & Tager-Flusberg, Chapter 5). Individuals with Velo-cardio-facial syndrome also tend to show an uneven neuropsychological profile with a discrepancy between verbal and performance IQ in 22q11DS, whereby verbal IQ (VIQ) exceeds performance IQ (PIQ) (Sundram & Murphy, Chapter 11).

COMORBIDITY

Another important clinical realization has been the recognition that neurodevelopmental disorders show high levels of comorbidities. For example, epileptic disorders are associated with intellectual disability, autism and psychiatric disorders (Miller & Tuchman, Chapter 21); attention-deficit/hyperactivity disorder (ADHD) is seen at high rates in many other neurodevelopmental conditions, including tuberous sclerosis (de Vries, Chapter 10), fragile X syndrome, autism spectrum disorders and developmental language disorders. It has also been recognized that, while specific genetic mutations account for only a minority of cases of autism spectrum disorders, autistic symptoms are very prevalent in individuals with severe intellectual disability with known genetic causes, including Cornelia de Lange syndrome and cri du chat syndrome (Oliver, Arron, Powis & Tunnicliffe, Chapter 12). However, severe intellectual disability is not universally associated with impaired social interest, as shown by the characteristic social engagement and social interest seen in Rubinstein–Taybi syndrome and Angelman syndrome (Dan & Pelc, Chapter 7). Other behavioural problems are commonly seen in individuals with intellectual disability; for example, sleep disorders are often present in children with epileptic disorders, particularly in individuals with Smith–Magenis syndrome (Sloneem & Udwin, Chapter 9).

INTERVENTION

Across the spectrum of neurodevelopmental disorders, approaches to intervention are very varied. For some disorders, such as developmental language disorder, these are solely psychoeducational (Paul & Gilbert, Chapter 17), while for others, such as Tourette syndrome (Robertson & Cavanna, Chapter 22) and ADHD (Wilens & Spencer, Chapter 13), the primary intervention is pharmacological, albeit increasingly in combination with cognitive behavioural approaches. Generic approaches that support cognitive and adaptive functioning, as well as the facility to communicate wishes and needs, are often used for individuals with global intellectual disability (Shulman, Flores, Iarocci & Burack, Chapter 18) as well as for children with disintegrative disorders (Volkmar, Chapter 20).

ADULT OUTCOMES

Until the last few decades the focus of a volume such as the present one would have been on children with developmental disorders. However, over the past few decades, as increasing numbers of children with the neurodevelopmental disorders covered in this handbook have been followed into adulthood and middle age, we now know more about outcomes than previously. For some conditions, such as autism spectrum disorders (Howlin & Charman, Chapter 15) prognosis is more variable than previously thought and is often highly dependent on environmental factors. It has also become apparent that mental health problems are common in adults with neurodevelopmental disorders, for example, in adults with fragile X syndrome (Schneider & Hessl, Chapter 4) as well as in individuals with intellectual disability of unknown origin (McCarthy & Bouras, Chapter 19). For other disorders particular issues arise, such as the well-established vulnerability to Alzheimer’s disease for people with Down syndrome (Carr, Chapter 2).

CONCLUSIONS

In most developed countries, the philosophy and organization of services has also changed so that the ambition is for individuals with neurodevelopmental disorders to live healthy and happy lives as part of a diverse and inclusive society. Over the next decades further discoveries in basic science, as well as clinical practice, will push forward the development of new interventions to ameliorate the medical, physical and behavioural sequelae that are commonly associated with intellectual disability and will further allow this ambition to be fulfilled.

REFERENCES

Schalock, R.L., Luckasson, R.A., Shogren, K.A., Borthwick-Duffy, S., Bradley, V., Buntinx, W.H.E., et al. (2007) ‘The renaming of mental retardation: understanding the change to the term intellectual disability’, Intellectual and Developmental Disabilities, 45: 116–124.

PART 2

Disorders with a Known Genetic Cause

1

Down Syndrome: General Overview

Deborah J. Fidler, & Lisa A. Daunhauer

BRIEF HISTORICAL PERSPECTIVE

It is difficult to identify when the physical and psychological features associated with Down syndrome were identified as constituting a specific phenomenon. Archeological evidence of the remains of a person with Down syndrome dates back to the seventh century (Roizen, 2007). Some posit that artistic renderings of individuals with Down syndrome can be found in paintings produced as far back as the 1600s (Volpe, 1986). But it is clear that by the middle part of the nineteenth century, recognition of the disorder had entered into the scientific literature. John Langdon Down (1866/1995) and Edouard Seguin (1866) each published work describing a cluster of symptoms associated with intellectual impairments in their patient populations. Down (1866/1995), for example, argued that the unique physical (mainly craniofacial) appearance of the cheeks, eyes, lips, and tongue was so distinct as to be caused by a common cause. He noted that ‘[s]o marked is this, that when placed side by side, it is difficult to believe that the specimens compared are not children of the same parents (p. 55).’ By 1877, the textbook On Idiocy and Imbecility was the first to include a special category on what was then termed ‘Mongolian idiocy’ (Ireland, 1877).

The subsequent search for the underlying etiology of these physical and psychological symptoms continued during the early part of the twentieth century and into the 1950s. Along the way, numerous erroneous etiologies for Down syndrome were put forth in the literature, including maternal tuberculosis during pregnancy and thyroid dysfunction (Clark, 1933; Muir, 1903). Other discoveries that have been borne out were made during this process, such as the recognition that advanced maternal age was a critical contributing factor in Down syndrome (Penrose, 1933, 1934).

There is a historical footnote to the discovery of Down syndrome that includes an unfortunate racial element to the earliest scientific work with this population. John Langdon Down’s original observations in 1866 placed the disorder within an ethnicity-related classification system, wherein the regrettable term ‘Mongolism’ was originated. Though this terminology left a legacy of derogatory racial connotations, Down’s views on ethnicity were actually enlightened for his time, as he argued that if a child with cognitive impairments of one race could show the ‘racial features’ of another race, it ‘proved that racial differences were not specific’ (Brain, 1967: p. 4). Down’s observations regarding the universality of such characteristics even led him to argue against the institution of slavery in the United States during the time of the US Civil War (Brain, 1967). The ethnic classification of such impairments was later publicly refuted by Down’s son, Reginald, a physician who worked in a home established by John Langdon Down for individuals with disabilities (Brain, 1967).

By 1959, Lejeune and his team had linked the disorder via karyotyping to the presence of an extra chromosome 21 (Lejeune et al., 1959). The following year, Polani and colleagues identified a case of Down syndrome caused by the translocation of material from chromosomes 15 and 21 (Polani et al., 1960). Mosaic Down syndrome was subsequently described in the literature in 1961 (Clarke et al., 1961).

EPIDEMIOLOGY

According to the most recent analysis of data from the US-based National Birth Defects Prevention Network, the prevalence of Down syndrome is 1 in every 732 live births when averaged across all maternal ages (Canfield et al., 2006). There is some evidence that the vast majority (80%) of trisomy 21 pregnancies result in miscarriage (Hook et al., 1995). Canfield et al. (2006) found a higher prevalence of Down syndrome in Hispanic families in the United States (prevalence ratio compared to non-Hispanic white families = 1.12) when compared to non-Hispanic white (prevalence ratio = 1.00) and non-Hispanic black families (prevalence ratio = 0.77). Possible explanations for this finding include differential use of prenatal health care, termination rates, and genetic or environmental factors, as well as artifacts of the research methodology employed in the Canfield et al. (2006) study (see Sherman et al., 2007 for a discussion).

Causation

The vast majority of cases of Down syndrome (90–95%) are caused by non-disjunction involving chromosome 21 during meiosis (oogenesis and spermatogenesis). The National Down Syndrome Project, a large-scale US-based epidemiological study of Down syndrome, reported that 93.2% of observed cases were caused by maternal non-disjunction and 4.1% were caused by paternal non-disjunction (Freeman et al., 2007). In a Spanish population-based study of the etiology of Down syndrome, Gomez et al. (2000) found that 88% of observed cases had maternal meiotic origin and 5.6% of the cases observed were of paternal meiotic origin. Of the maternal cases in the Gomez et al. (2000) study, 90.6% occurred in during the first meiotic division and 6.2% occurred during the second meiotic division. In the paternal cases, half occurred during meiosis I and half occurred during meiosis II. There is some suggestion, however, that some meiosis II errors may actually originate in meiosis I (Sherman et al., 2005).

Though non-disjunction during meiosis is the main cause of Down syndrome, accounting for the vast majority of cases, there are two other etiological mechanisms. Roughly 1% of cases of Down syndrome are mosaic in nature (Connor & Ferguson-Smith, 1997). Mosaicism results from errors in mitosis following fertilization, leading to two different cell lines in a developing zygote/embryo (Connor & Ferguson-Smith, 1997). One cell line contains the normal 46 chromosomes and a second cell line contains the additional chromosome 21. In the majority of cases (80%), mosaicism resulted from non-disjunction in mitosis in a zygote that already had trisomy 21. In the remaining cases (20%), mosaicism occurred in a euploid zygote (Connor & Ferguson-Smith, 1997).

Down syndrome can be caused by a translocation of genetic material between chromosome 21 and another chromosome (Connor & Ferguson-Smith, 1997). This is the cause of roughly 4% of case...

Table of contents

• Cover Page
• Title
• Copyright
• Contents
• Contributors
• PART 1 OVERVIEW
• PART 2 DISORDERS WITH A KNOWN GENETIC CAUSE
• PART 3 DISORDERS WITH COMPLEX OR AS YET UNKNOWN CAUSES
• PART 4: ENVIRONMENTALLY INDUCED DISORDERS
• Author Index
• Subject Index