Children With Down Syndrome Can Learn

Teaching Down Syndrome

Although Home is Where the Smart Is is packed with information in its 104 pages, it is not an exhaustive work. It's a consideration of the basics of teaching your child with Down syndrome, starting from birth through the foundational elementary years. What's inside: Why Down syndrome is Not mental retardation .page 14 How you really can reat Down syndrome. . page 17 How you can save frustration and diapers with an old method of potty training . pg 49 How you can keep that tongue from sticking out . page 38, 69 The fastest way to teach your child to read . page 60 Developmental milestones, word lists, websites and resources . page 90 And, if you must be involved with the public school system, basic guidelines for Individual Educational Plans (Ieps) and 15 snippy questions to ask educators.

Teaching Down Syndrome Summary


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Down syndrome Differences in the Brain

Down syndrome occurs in one out of every 800 to 1000 live births (National Down syndrome Society, 1999). It can usually be diagnosed early due to many phenotypic differences and is conclusive with a blood test. Most individuals with Down syndrome have an IQ that falls within the mild (IQ 50 to 70) to moderate range (IQ 35 to 50) of mental retardation (National Down syndrome Society, 1999). An initial pathological inspection of the Down syndrome brain appears to reveal a reduced brain weight (Benda, 1969 Benda, 1971 Friede, 1975 Urich, 1976 Whalley, 1982 Wisniewski et al., 1985 Coyle et al., 1986). Benda (1971) also reported a compression of the occipital lobes. A few studies have reported a narrowed superior temporal gyrus in approximately 50 of cases (Friede, 1975 Urich, 1976 Zellweger, 1977 Kemper, 1988). Two separate studies have also reported a hypoplasia of the frontal lobes (Benda, 1971 Crome & Stern, 1972). Other cortical abnormalities are reported on neural density. Many...

Down syndrome

Down syndrome is the most common cause of mental retardation and it affects approximately 1 in 1000 live births. The incidence rises with advancing maternal age at the time of conception (15-29 years, 1 in 1500 30-34 years, 1 in 800 35-39 years, 1 in 270 40-44 years, 1 in 100 over 45 years, 1 in 50). Approximately 94 per cent of cases of Down syndrome are caused by trisomy 21, 3.5 per cent by translocation, and 2.5 per cent by mosaicism. The cause of trisomy 21 is not known, but the general likelihood of recurrence is 1 per cent. Those with Down syndrome have characteristic facial and other clinical features which include short stature, round skull, brachycephaly, typical eye signs such as 'mongoloid slope' of the palpebral fissures, the 'epicanthic fold' in which the upper eyelid overlaps the lower at the inner canthus, and 'Brushfield spots' (a fine white speckling of the iris). Other eye abnormalities include premature development of cataracts, myopia, blocked tear duct,...

Additional Components of the Alzheimers Pathology

In an Alzheimer's diseased brain, the abnormalities of the key proteins Ap and tau result in a complex pathological cascade. The relative importance of the various components and the sequential evolution of this cascade is the subject of ongoing investigations. The simplified scheme of Fig. 3 attempts to highlight some of the most notable participants of this pathological cascade. Neurons possess APP molecules in their cell membrane and also in membranes of cell organelles (typically rough endoplasmic reticulum, Golgi complex, endosomes). In the cell surface the action of a-secretases (1) releases soluble APPa fragments which are regarded as neurotrophic molecules (Fig. 3). This is the APP nonamyloidogenic pathway, precluding the formation of Ap peptides. The APP amyloidogenic pathway (3) involves the sequential cleavage of APP in its p and y sites releasing Ap peptides. This process apparently involves an intracellular cycle and some of the Ap material accumulates abnormally in...

Cholinergic Neurodegeneration in Alzheimers Disease

Abstract Neurotrophins play an important role in the survival, differentiation, and maintenance of neurons selectively involved in a number of disorders of the nervous system. Nerve growth factor (NGF) plays a vital role for basal forebrain cholinergic neurons (BFCNs), including the maintenance of the cholinergic phenotype in adults. Recognition of this role has suggested the use of NGF to ameliorate the loss of these neurons in Alzheimer's disease (AD). While clinical studies directed at supplying NGF to patients continue to be pursued, fundamental questions remain as to the relationship between selective vulnerability of cholinergic neurons and the actions of NGF. In this chapter, we review the structure and function of the basal forebrain cholinergic system, its role in higher cognitive functions, and the importance of NGF actions on these cells. Studies that link changes in NGF signaling to the degeneration of BFCNs are then discussed, as are current approaches to NGF-related...

Failed NGF Signaling in Alzheimers Disease

These findings suggest two views for how NGF signaling might be disrupted in AD. In the first, reduced availability of NGF receptors would play a defining role in BFCN degeneration by compromising NGF signaling and the retrograde transport of such signals to the cell bodies of these neurons (Mufson, Kroin, Sendera, & Sobreviela, 1999 Salehi et al., 2003 Salehi et al., 2000). In the second, a failure in retrograde signaling unrelated to receptor availability would be responsible. On the basis of in vitro and in vivo experiments, this could result in downregulation of receptor gene expression and a further decline in NGF delivery. Each view is consistent with the evidence suggesting continued synthesis and presence of NGF in the BFCN projection areas together with reduced levels of NGF in BFCN cell bodies. Discerning between the alternatives requires experiments in mouse models in which BFCN pathogenesis can be examined. To study these alternatives, during the last few years, we have...

Minor group antigens also may uncommonly contribute to

Hemolytic anemias, transfusions, and trauma associated with hematomas result in increased bilirubin load and are causes of indirect hyperbilirubinemia in any age group. Infants with galactosemia and hypothyroidism may present initially with indirect hyperbilirubinemia in the newborn period. Congenital infections (eg, cytomegalovirus, toxoplasmosis) that cause systemic illness may be associated with hemolysis and indirect hyperbilirubinemia, in addition to hepatitis and direct hyperbiliru-binemia. Indirect hyperbilirubinemia may be exaggerated in the presence of the following risk factors Asian or Native American race, prematurity, polycythemia, male sex, Down syndrome, oxytocin induction, delayed stooling, and having a sibling with a history of neonatal jaundice.

Chromosome Abnormalities in Clinical Medicine

Cytogenetics became of clinical interest in the late 1950s, when the association between particular syndromes and chromosomal aneuploidy (e.g. Down syndrome and trisomy 21) was established. A decade later banding techniques were developed that allowed the unequivocal identification of individual chromosomes and their subdivision into visually recognisable zones or 'bands'. More recently, the development of FISH (fluorescence in situ hybridisation) has allowed chromosome structure to be examined in even finer detail. One outcome has been the delineation of a group of syndromes that are characterised by sub-microscopic chromosome deletions (e.g. Williams syndrome and microdeletion of chromosome 7) which can be delineated by specific, suitably labelled DNA probes. Cytogenetics is now used as a diagnostic tool for a variety of clinical disciplines and increasingly in the diagnosis and management of cancer.

Prenatal Genetic Diagnosis

Detection of trisomy 21 (Down syndrome) is the most common indication for prenatal diagnosis in the United Kingdom, accounting for approximately 37 000 procedures per annum. Rapid interphase FISH on uncultured cells from an amniotic fluid sample allows a result for chromosome 21 copy number to be obtained in 24-48 h rather than the 7-14 days required for conventional chromosome analysis. The screen can also be set up to co-detect aneuploidy for 13, 18, X and Y (Figure 4.2(b)). In addition, enumerators for the sex chromosomes can allow for rapid fetal sexing, for instance in cases of sex-linked genetic disorders. The ability to reliably and efficiently access fetal cells (or fetal DNA) from the maternal circulation for genetic diagnoses would clearly be of considerable clinical value. FISH has been used to successfully determine chromosome copy number after isolation of suitable target cells e.g. nucleated red blood cells (NRBCs) . Typically, methods involve one or more enrichment...

Differential Diagnosis

Consider toxicity, metabolic encephalopathy, chromosomal disorder (eg, Prader-Willi syndrome, trisomy 21), infection, periventricular leukomalacia, cerebrovascular accident, hypoxic ischemic encephalopathy, trauma (intracranial hemorrhage), cerebral palsy, benign congenital hypotonia, mass (tumor, cyst).

Cytogenetic Studies May Help To Localise Genes Contributing To Bipolar Disorder

One of the earliest areas of interest was chromosome 21, stemming from the longheld idea that Down's syndrome (trisomy 21) as a condition is mutually exclusive with bipolar disorder. This is not the case, and there are good descriptions of both mania and depression in Down's syndrome, although the risk of bipolar disorder may be decreased, and unipolar disorder is held by some to be increased in frequency. Trisomies involving the sex chromosomes have also been implicated, but the initial studies were not well controlled, and more recent work has not provided good evidence that they are a substantial risk factor for bipolar disorder (Mors et al., 2001).

Hereditary and Genetic Aspects Genetic Syndromes

The proportion of childhood leukemia due to inherited genetic mutations is quite small, with estimates ranging from 2 to 5 percent.73-75 Down syndrome is the most common genetic syndrome associated with childhood acute leukemia, with afflicted children experiencing nearly a 20-fold increased risk of developing either ALL or AML.76 Intriguingly, there are reports of as high as a 600-fold increased risk for one particular subtype of myeloid leukemia (AML-M7).77 It is unknown why children with Down syndrome are at such an increased risk. Several research groups are focusing attention on genes on chromosome 21, given that one of the most common acquired abnormalities present in the leukemia cells of children without Down syndrome is an extra copy of chromosome 21.78-80 Other syndromes associated with childhood leukemia include Bloom syndrome, ataxia telangiectasia, Shwachman syndrome, and neurofibromatosis 1.81-84

Neurological Disorders and Neurodegenerative Diseases

Enhanced interleukin production in the central nervous system has been observed following injuries or local infections and in neurodegenerative diseases, such as Alzheimer's disease and in trisomy 21. Enhanced IL-1 synthesis is thought to occur in early stages of Alzheimer's disease, provoking the induction of jS-amyloid precursor synthesis and gliosis.

Hereditary and Genetic Aspects Familial Patterns and Associations

Although there are several case reports of more than one case of leukemia occurring in the same family, these associations could either reflect similar environmental influences, or shared genetic factors.73,149,150 As with childhood leukemia, however, these familial associations only account for a very small proportion of cases. In contrast to twin studies in children, studies in adults do not show any concordance for the development of leukemia.151 Interestingly, one report found an increased risk of leukemia among parents of children with Down syndrome.152 Finally, a recent report suggested that although the risk of leukemia in individuals with Down syndrome is highest in childhood, there is an elevated risk throughout life.153

Rheumatologic or inflammatory disorders

Infants with Down syndrome can develop a transient leukemoid reaction with extremely high WBC count, consisting mostly of neutrophils and immature myeloid elements, which resolves spontaneously. Blood smear can resemble that seen in chronic myelogenous leukemia.

What Makes The Brain Intelligent

What can we learn about the neurobiological basis of intelligence by studying people with aberrations of intelligence Autism, mental retardation, and Down syndrome manifest a variety of intellectual deviations from low intelligence quotient (IQ) to aspects of genius. Most research on these disorders has focused on the underlying etiology. Independently, intelligence researchers have sought to understand the neurobiology of intelligence. We will review brain research in autism, mental retardation, and Down syndrome, and try to relate relevant findings to intelligence research. Neuropathological data allow an in vitro look at the brain. The advent of brain imaging technologies such as Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) allow an in vivo look at the working brain. After a brief review of some animal work and intelligence research, we will review studies on autism, mental retardation, and Down syndrome, especially those that include an...

Prevention of mental disorders

Mental disorders with known aetiology this mostly includes those disorders demonstrated to have an organic basis, ranging from the 'historical' general paresis and dementing disorders (e.g. vascular dementia, pellagra, and dementias associated with infectious and parasitic diseases such as malaria and HIV infection) to several forms of mental retardation (Down syndrome, fetal alcohol syndrome, phenylketonuria, and mental retardation due to iodine deficiency).

Mental disorders with known aetiology

As for mental retardation, up to 15 per cent of cases could be prevented by dealing with the causes that lead to it. A recent WHO publication (2) has set detailed guidelines for the prevention of some forms of this condition, namely, Down syndrome, fetal alcohol syndrome, phenylketonuria, and iodine deficiency syndrome. These preventive actions are both efficient and affordable even in very poor regions of the world. The primary prevention of Down syndrome can be successfully achieved through the control of the age at which women become pregnant ideally, the age range can be very useful for the in utero diagnosis of Down syndrome (as well as of other problems and malformations). Wherever it is culturally, morally, and legally acceptable and permitted, a therapeutic abortion can be seen as another primary prevention measure. Fig. 1 Estimated risk of Down syndrome by related age. (Data from Gottesman.(5))

Other Mutations Implicated in the Pathogenesis of AML

The function of a number of key transcription factors that regulate normal hematopoietic development is disrupted in AML due to the presence of inactivating or dominant negative mutations (see Table 30-3). The first such example to be identified involved the AML1 gene, which was found to be mutated in familial platelet disorder (FPD reviewed in Reference 2). This rare autosomal dominant condition is characterized by progressive pancytopenia and dysplasia and ultimately progresses to AML in a high percentage of cases. AML1 is mutated in approximately 3 to 5 of sporadic cases of AML, particularly those with acquired trisomy 21 and cases with minimal differentiation (French-American-British FAB type M0 details of FAB classification of AML are provided in Reference 7). Indeed, AML1 mutations are detected in up to 25 of M0 cases and are frequently biallelic. GATA1 is a key transcription factor involved in megakaryocytic differentiation and is mutated in cases of transient abnormal...

Confirmed risk factors

At the present time, only four risk factors for Alzheimer's disease can be regarded as confirmed beyond reasonable doubt (1314) old age, a family history of dementia, Down syndrome, and apolipoprotein E (ApoE) genotype. Down syndrome People with Down syndrome always develop Alzheimer's disease pathology before the age of 40 years. Their increased risk is due to their having an extra copy of the b-amyloid precursor gene, which is on chromosome 21 (see above). However, declines in everyday functioning are often not seen until a much older age. The reason for the lag between pathology and clinical changes is not understood.

What are Possible Causes to the Low IQ of Mental Retardation

Pulsifer (1995) reviewed pathological and imaging data of the five major identifiable prenatal causes of mental retardation in order to identify the neuropsychology of mental retardation. After a review of the literature, Pulsifer reported on both neuroanatomical abnormalities and cognitive deficits in each and every disorder. After reviewing fetal alcohol syndrome, Down syndrome, fragile X syndrome, Prader-Willi syndrome, Angelman syndrome and idiopathic mental retardation, Pulsifer found only two neuroanatomical sites with abnormalities common to all disorders the hippocampus and cerebellum. Cognitive deficits common to all disorders were in attention, sequential information processing, and short-term memory. Functional analysis of idiopathic mental retardation is very much in its infancy. Most functional information on idiopathic mental retardation has been obtained using GMR with PET scanning. Chugani and colleagues (1987) performed the first functional study on individuals with...

Pathophysiology of OSAS

The etiology of OSAS is uncertain and multifactorial. For OSAS to occur there must probably be a combination of three factors altered airway structure, diminished neuromuscular control, and miscellaneous factors, such as genetic and hormonal influences. Thus, one child with a narrow airway due to adenotonsillar hypertrophy with a high ventilatory drive may not develop OSAS. An intense local and systemic inflammation tends to presents in these patients. In the upper airway, this process may promote oropharyngeal inspiratory muscle dysfunction and amplify both upper airway narrowing and collapsibility thereby worsening the frequency and duration of apneas during sleep. Adenotonsillar hypertrophy is the commonest condition associated with childhood OSAS. The lymphoid tissue in the upper airway increases in volume from birth to 12 years of age with a peak between 3 and 6 years of age. This coincides with the peak incidence of childhood OSAS. Craniofacial anomalies due to narrowing of the...

Frequencies in populations Factors affecting frequencies

These processes give rise to variation in prevalence in different communities and at different times for all degrees of intellectual impairment. This is not surprising, given the varying social determinants of population frequency of the causes of neurological impairment. These social factors (e.g. diet in neural tube defects patterns of fertility in Down syndrome alcohol price and supply in fetal alcohol syndrome consanguinity in recessive genetic disorders) are most likely to offer scope for prevention. Preventive interventions have been successful for some disorders in some communities, creating another source of variation in frequency.

Descriptive epidemiology of severe intellectual impairment IQ

Point prevalence varies between similar birth cohorts (concurrent age groups) in different communities (e.g. 1.62 1000 children born 1951-55 in Salford, United Kingdom, and 7.34 1000 children born in 1957 in Amsterdam). Greater variation is expected in developing countries, (lJ) especially where there is one dominant cause such as iodine deficiency disease, where congenital hypothyroidism can affect more than 10 per cent of village populations. Down syndrome is often the largest aetiological group, especially in communities with traditions of late marriage, large families, and taboos against contraception and or abortion, and where early mortality is low. Mortality and survival vary greatly, generally related to the 'development status' of the community. 3. A similar pattern of temporal variation is common throughout the developed world. Age-specific prevalence was generally low (1.8-4.0 in 1000) for children born in the early 1950s, and high (3.3-5.5 in 1000) for those born in the...

Developing countries17

Rigorous studies are more difficult and good record systems less common in developing countries, so there are few reliable sources for estimating prevalence, but data available suggest differences related to the varying spectrum of organic causes, mortality, and social situations. fy,1.6.) Developing countries are not all the same for example the high infant mortality of most African countries is not shared by China. In some, cretinism due to iodine deficiency disease is an overwhelming cause and can affect over 10 per cent of village populations before salt iodization or similar programmes have much impact. Children with Down syndrome do not generally survive in communities with high infant mortality.

Medical and genetic issues

The availability of a thorough medical assessment is a necessary component of the psychiatric assessment of children with mental retardation to both establish the cause of the mental retardation and define the presence of any associated medical condition that might contribute to, or complicate, the emotional and behavioural problems. Young people with mental retardation have an increased risk of medical problems particularly those that involve the brain, such as epilepsy and cerebral palsy. Specific medical complications are associated with known causes of mental retardation such as cardiac and bowel problems that occur in Down syndrome and hearing impairment associated with rubella embryopathy.

Behavioural phenotypes

Down syndrome The overall rates of psychopathology are lower than in other children with mental retardation, but at around 20 to 30 per cent are still higher than the general population2.' which dispels the myth that these children are always easy 'Prince Charmings'.(30) Children with Down syndrome are more likely to present with externalizing disorders such as oppositional conduct and attention-deficit problems. (31) This pattern changes in adolescence and young adulthood when persons with Down syndrome are more likely to suffer affective disorders and dementia. (32>

Physical Exam Key Points

Airway, breathing, circulation (ABCs). Focus on the ABCs. Is airway patent Check for potential obstruction (eg, copious secretions, loose teeth, large tongue, small jaw, tonsillar hypertrophy). Children with certain genetic syndromes, such as trisomy 21 and Pierre-Robin sequence, pose intrinsic increased risk based on their anatomy.

Prevalence of particular mental illness

A prevalence rate of about 12 per cent for both mild and severe dementia in the mentally retarded who are aged 65 and older is similar to that found in the general public.(33) Both senile dementia and cerebral arteriosclerotic dementia occur. The predisposition of people with Down syndrome to develop Alzheimer-type dementia during middle age is well established.(33) The prevalence rates of clinical dementia range from 6 to 45 per cent, although an Alzheimer-type neuropathology is virtually universally present in the brains of individuals with Down syndrome dying after the age of 35 and increases in magnitude with the years.

Chapter References

Epilepsy in Down syndrome. In Epilepsy and mental retardation (ed. M. Sillanpaa, L. Gram, S.I. Johannessen, and T. Tomson). Wrightson Biomedical, Petersfield. 25. Stafstrom, C.E. (1999). Mechanism of epilepsy in mental retardation insights from Angelman syndrome, Down syndrome and fragile X syndrome. In Epilepsy and mental retardation (ed. M. Sillanpaa, L. Gram, S.I. Johannessen, and T. Tomson), pp. 7-40. Wrightson Biomedical, Petersfield.

Elderly people with mental retardation Life expectancy

People with mental handicap have an increased risk of death compared with the general population. Whereas the majority of deaths (83 per cent) in the whole population occur in people aged 65 years and over, less than 50 per cent of deaths among people with mental retardation are in this age group. (25> However, lifespan is known to be increasing within this group, especially for people with Down syndrome, as a result of medical advances, better quality of care, and new surgical techniques.(26>

Mental health needs

Psychiatric and behavioural disorders increase with age. Among people with Down syndrome the neuropathological changes of Alzheimer's dementia are universal after the age of 35 years, although clinical dementia is not inevitable. Dementia occurs more frequently among elderly people with mental retardation than among the general population, and with the increasing longevity of people with mental retardation the number with dementia is rising. (37) The distress that can result from dementia, both for the elderly people and for their carers, requires understanding and effective management.

The effect of diagnosis

Down syndrome is the most common disorder recognizable at birth and known to be likely to be associated with mental retardation. Despite screening in early pregnancy, it is still common but is now often the child of younger parents. Genetic diagnosis of unusual children is more rapid than hitherto. Parents are almost without exception relieved by a clear diagnosis, an explanation of why it has happened, and an estimate of future risk. Most families are also greatly helped by meeting others with similar problems. Parent support groups for each specific diagnosis are now worldwide and recruits are quickly introduced to information via the Internet. The diagnosis can have implications for other members of the family, as with fragile X syndrome or tuberose sclerosis, as some relatives may have a minor form or be carriers, with a risk of further children in the family being affected. Genetic counselling is essential and may be requested very early on, even preconception. To be...

Indications For Chromosomal Evaluation

Human Metaphases

Women with AMA are at increased risk of carrying a fetus with a chromosomal abnormality, especially trisomy 21, and are routinely offered an amniocentesis. A number of maternal serum screening tests such as maternal serum a-fetoprotein, unconjugated estriol, human chorionic gonadotrophin, and dimeric inhibin A have been developed. Women with abnormal values are also at higher risk for certain chromosomal anomalies and, therefore, are candidates for amniocentesis. This is especially important for women under the age of 35 because most cases of Down syndrome occur in this group, but these women are not generally offered amnio-centesis on the basis of age alone. Amniocentesis is also indicated when one of the parents is known to be a carrier of a balanced chromosomal rearrangement that could be passed to offspring in an unbalanced form. In addition, this procedure is performed as a follow-up to the finding of fetal anomalies on ultrasound and to clarify possible mosaicism seen...

Constitutional Chromosomal Abnormalities

Microsatellite Instability

Trisomy 21 (Down syndrome) is the most common of all autosomal trisomies to survive to term and is seen in 1 in 700 live births. Even so, 60 of cases of trisomy 21 abort spontaneously. About 94 of cases of trisomy 21 are the sporadic, noninherited type that result from meiotic nondisjunction, whereas 4-5 result from inherited Robertsonian translocations or isochromosomes of the long arm of chromosome 21, and 1-2 are mosaic, resulting from mitotic nondisjunction early in embryogenesis. A very small portion of full trisomy 21s are the result of gonadal mosaicism of a parent. This phenomenon accounts for the rare cases of recurrent complete tri-somy 21 reported in some families. Mosaicism usually results in a milder phenotype. Life expectancy for individuals with Down syndrome is greater than 45 yr (27). There are dozens of relatively minor abnormalities seen in trisomy 21 and no patient exhibits all of them. Most of these findings are not particularly abnormal by themselves, but...

Sleep Disordered Breathing in Special Populations

Half of all children with Down syndrome have SDB. However, symptoms of daytime sleepiness and sleep disruptions at night may be due to non-neurological factors such as maxillofacial abnormalities, large tonsils or adenoids, micrognathia, large tongues, or other abnormalities. Sleep disorders often occur in patients with neuromuscular disease because of associated weakness in respiratory muscles, which is further exacerbated by hypotonia during sleep. In disorders such as Duchenne's muscular dystrophy, daytime pulmonary function studies do not predict the degree of apneic events during sleep. Rather, these patients can have nocturnal oxygen desaturation, significant sleep fragmentation, recurrent hypoventilation, and reduced REM sleep. These patients are also at increased risk for aspiration during sleep. Diagnosis and treatment of SDB in these patients can be an important part of comprehensive management.

Schizophrenia as a disorder of brain maturation

There is evidence from clinical research implicating aberrant neurodevelopmental processes in the pathophysiology of schizophrenia, (.33> but there is also a growing literature suggestive of progressive deterioration in the disease for at least some patients. (3i> It should be noted that abnormal neurodevelopmental processes are not mutually exclusive of neurodegenerative mechanisms in the pathogenesis of complex neuropsychiatric disorders. Indeed, while some genetic disorders are purely developmental (e.g. fragile X syndrome) and others purely neurodegenerative (e.g. Huntington's disease), some have both developmental and degenerative pathologies (e.g. Down syndrome). Based on the neuropathological literature of the last 30 years some suggestions can be made concerning the pathophysiology of schizophrenia.

Behavioural phenotypes in relation to mental illness

Down syndrome has always been associated with specific patterns of language, cognitive, and social development. In most studies these persons were found to exhibit muted affect and have deficient language development, and yet they showed particular strengths in socialization. The tendency for such individuals to develop Alzheimer dementia has been often described. The occurrence of affective disorder among Down syndrome subjects had attracted the attention of scientists recently. In an examination of the psychiatric disorders of a group of 378 adults with Down syndrome, Collacot et al.(42,) found presenile dementia in 4.3 per cent of the subjects (versus only 0.3 per cent of controls with other forms of mental retardation). One or more episodes of depressive illness were diagnosed in 11.3 per cent of the Down syndrome patients, but in only 4.3 per cent of the controls with other types of mental retardation. Other types of psychiatric and behavioural disorders were significantly less...

The Examination Of The Pediatric Patient

Congenital craniofacial syndromes are associated with OSA. Children who have syndromes with craniosynostosis, such as Apert's syndrome, Crouzon's disease, Pfeiffer's syndrome, and Saethre-Chotzen syndrome abnormalities of the skull base and accompanying maxillary hypoplasia may have nasopharyngeal obstruction (126). Children with syndromes that involve micrognathia, such as Treacher Collins syndrome, Pierre Robin syndrome, and Goldenhar's syndrome, become obstructed at the hypopharyngeal level and children with trisomy 21 often have a narrow upper airway combined with macroglossia and hypotonic musculature predisposing them to OSA (126).

Acute Megakaryoblastic Leukemia M7

Acute megakaryoblastic leukemia (AMkL) is a rare form of AML. It occurs particularly in infants children younger than 2 years and in adults older than 50 years and represents 10 percent of childhood AML and 0.5 to 1 percent of adult AML.98,99 AMkL is a heterogeneous disease, comprising at least three entities M7 with t(1 22)(p13 q13), M7 in Down syndrome (DS), both found in infants and young children, and M7 without DS and without t(1 22), the latter having a typical AML age distribution increasing with age.100

Syndromal mental retardation

A number of syndromes associated with mental retardation have been found to be due to chromosomal rearrangements among which Down syndrome (trisomy 21) is by far the most common (accounting for about a third of all cases with moderate to severe retardation). Chromosomal rearrangements can be extremely complex, as can the nomenclature used to describe them. Abnormalities of the number of chromosomes result in aneuploidy. Deletion of part or an entire chromosome is termed monosomy (or haploinsufficiency) an extra copy of either part of or an entire chromosome is called trisomy. A general term to describe either loss or excess of chromosomal material is aneusomy. Both Down syndrome and Turner syndrome are due to an abnormal number of chromosomes, an extra chromosome 21 in the case of Down syndrome and a single X (without a Y) in the case of Turner syndrome. Epstein has argued that the phenotypes of the aneuploid syndromes (of which these are just two examples) cannot be due to...

Neurogenetic syndromes with behavioural phenotypes

Comprehensive study of children with different neurogenetic disorders may increase our appreciation for the relative contribution of genetic variables in the pathogenesis of specific affective and behavioural disorders. Behavioural phenotypes have been studied most extensively in Down syndrome (mimicry), (8) fragile X syndrome (gaze aversion, hyperkinesia, autistic-like behaviour),(9) Williams syndrome (sociability, hyperverbal behaviour, and visuospatial deficits), fy0,,11 Lesch-Nyhan syndrome (compulsive self-injury and aggression), ( 2.,13 and 14 and Prader-Willi syndrome (hyperphagia, obsessive-compulsive behaviour). l6 The number of identifiable behavioural phenotypes is growing with careful observations of behaviours in neurogenetic disorders. (5) Besides behaviours, particular temperamental features have also been considered in these disorders. However, when studying temperament, the appropriate measures must be chosen. For example, when Down syndrome, proposed to be linked to...

The Molecular Line

These efforts continued in the 1950s with the establishment of the number of human chromosomes at 46 and the discovery of the chromosome abnormalities Down syndrome (trisomy 21), Turner syndrome (45,X), and Klienfelter syndrome (47,XXY) (13). This was an impressive start for the discipline of cytogenetics. Although these advances are some of the earliest representations of how medical molecular biology is practiced, the fundamental science was advancing at a remarkable rate. Chargaff determined that the ratio of the nucleic acid bases was always 1 1, an important breakthrough for determining the structure of DNA (13,14). Combined with the crystallography work of Rosalind Franklin and Maurice Wilkins that showed an orderly, multiple polynucleotide chain, helix structure, James Watson and Francis Crick were able to propose a structure for DNA (16).

Epicanthal Folds

A crescentic fold of skin usually extending bilaterally between the upper and lower eyelids and covering the medial angle of the eye. This rare congenital anomaly is harmless and typical in eastern Asians. However, it also occurs with Down's syndrome (trisomy 21 syndrome). Thirty per cent of newborns have epicanthal folds until the age of six months. Where one fold is more pronounced, it can simulate esotropia. The nasal bridge becomes more pronounced as the child grows, and most epicanthal folds disappear by the age of four.

Cycloplegic Agents

Systemic toxicity is hallmarked by flushing (reddening) of skin, dryness of skin and mouth, irregular and rapid pulse, hallucination, speech difficulty, and loss of coordination. Physicians, technicians, and parents should all be aware of these symptoms, especially when cycloplegics are given to children. Also, these drugs should be administered carefully to those with Down syndrome, who tend to have an increased response to these medications.

MtDNA maintenance

Damage and extends the life span of transgenic Drosophila melanogaster (85). Other evidences for this hypothesis are the high level of oxidative damage and its accumulation with age, the correlation between oxidative damage and maximum life span potential, and the increased oxidative damage and premature aging found in people with Down syndrome (86).

Glutamine excess

Elderly individuals, patients with Alzheimer's dementia, or Down syndrome showed increased glutamine toxicity in peripheral lymphocytes compared to controls 72 . Aside from these sporadic and somewhat anecdotal reports of toxicity, glutamine appears to be quite safe. Even with high intakes of glutamine, the concentrations of ammonia and glutamate are not greatly increased, and the plasma concentrations of other amino acids, hormones, and electrolytes are not altered 85 .

Alzheimers Disease

Alzheimer's disease is associated with diffuse neuron injury and death, with senile plaques and neurofibrillary tangles. The average duration of the disease is 10 years, during which afflicted persons progress from mild memory loss to the need for 24-hour supervision to total dependency and death. Risk factors for Alzheimer's disease are age, a family history of the disease, and Down syndrome.


The first chromosomal abnormality was described by Lejeune in 1959. He discovered that there was an extra copy of chromosome 21 in Down syndrome (4). Later that same year, other researchers reported that Turner syndrome had a 45,X chromosome complement (5) and that Klinefelter syndrome had an 47,XXY chromosome complement (6). A woman with 47,XXX was also described (7). The following year, the other common autosomal trisomies (trisomy 13 and 18) were described (8,9). Also in 1960, Nowell and Hungerford described the first consistent chromosomal change seen in cancer. They noticed that in chronic myelogenous leukemia (CML), one chromosome 22 was always unusually small. They dubbed this small chromosome the Philadelphia (Ph) chromosome after the city in which it was discovered. Lejeune described the first deletion syndrome in 1963 and 1964 when he reported that deletion of the short arm of chromosome 5 (cri du chat syndrome) was seen in patients with a catlike cry and phenotypic...

Postnatal Diagnosis

Interphase FISH can be performed on uncultured blood smears (Figure 4.2(c)) or cells grown in short-term in vitro culture and a result obtained within 24 h (McKeown et al., 1992). This approach can also be used for rapid confirmation of chromosomal sex in newborns with ambiguous genitalia.

Concluding Remarks

Down syndrome is associated with an estimated 20-fold increased risk. Neurofibromatosis type 1, Bloom syndrome, ataxia telangiectasia, and Langerhans cell histiocytosis, among others, are associated with an elevated risk. Down syndrome and neurofibromatosis 1 are strongly associated. Familial monosomy 7 and several other genetic syndromes are also associated with increased risk.

Mental disorders

Therefore a strategic shift is necessary in order to obtain greater efficiency in the successful prevention of some mental disorders. The first step is for an effort to be as specific as possible in relation to the target condition for instance Down syndrome or phenylketonuria instead of mental retardation, fetal alcohol syndrome and delirium tremens instead of alcoholism, and vascular dementia and dementia following brain injury instead of dementia in general.


Based on this review of autism, Down syndrome, and mental retardation, six factors may be linked to intelligence. These are brain size, brain metabolism, neu-ronal dendritic development, cerebellum size, brain stem size, and hippocampus size. It is interesting to note the lack of cortical areas implicated in this review. Higher intelligence is traditionally thought to be located in the frontal lobes. However, the frontal lobes are rarely implicated in the literature. It is important to discern if the abnormality is causing a low intelligence or if the low intelligence is causing the abnormality. It is equally important to keep in mind that these abnormalities may be affecting performance and not intelligence. Anderson (in press) recently completed an analytic review of the brain size IQ relationship. Anderson reviewed studies of brain size and intelligence and reported positive correlations of anywhere from r 0.35 to r 0.69. Autism is frequently associated with macrocephaly or a big...

MDS in Children

MDS in childhood accounts for less than 10 percent of all malignancies in this age group,186 and very heterogeneous disease. It may develop de novo or after chemotherapy or radiation therapy. Constitutional conditions such as Down syndrome are present in one-third of children with MDS.187 The classification of MDS in childhood using FAB criteria has been the subject of some controversy.188 The frequency of FAB subtypes of MDS in childhood differs from those observed in adults. Approximately 50 percent of children with de novo MDS have chromosomal abnormalities, with monosomy 7 (-7) or partial deletion of the long arm of chromosome 7 seen in 30 to 40 percent of cases (H. Hasle, personal communication). Monosomy 7 is found in all MDS subgroups. In addition hematological features of some nonclonal disorders such as mitochondriopathies may be indistinguishable from the true clonal MDS RARS.185,188


Infantile spasms occur usually at the ages of 4 to 6 months and in 90 per cent of cases during the first year of life. The events resemble the Moro reflex with sudden, brief flexion of neck and trunk, raising both arms forwards or sideways, sometimes with flexion at the elbows, and flexion of legs at the hips. Less often, the legs extend at the hips. At the early stage flexion of neck may be the only or main feature this may be followed by more complex and dramatic attacks later on. A cry is often associated with the attack either as part of the attack or occurring afterwards as an expression of disquiet. The spasms are usually symmetric, but may be asymmetric or even unilateral. The EEG is chaotic with slow waves of high voltage intermixed with diffuse or asynchronous spikes in both hemispheres or in the contralateral hemisphere in unilateral cases. This pattern is called hypsarrhythmia. Infants with unilateral spasms need to be examined using a positron emission tomography scan, as...

Health needs

There is an increased risk for a number of medical conditions in people who have Down syndrome,(34) including sensory impairments, thyroid disease, leukaemia, and atlantoaxial instability. The later sequelae of congenital heart disease include pulmonary hypertension and congestive heart failure.

Mental illness

In the early months following the birth of a child recognized as having a major developmental disorder such as Down syndrome, there was clearly much distress and disappointment, but little evidence that the mothers had a higher incidence of postpartum psychiatric disorder. Later in the childhood of the affected child, particularly in families with many other problems, depression was more common in the mothers of children with Down syndrome than in mothers of normal children. But when the mothers of children with a variety of disorders all producing intellectual deficit were compared with mothers of children with Down syndrome, there were less reported health problems in the Down group. Children with brain damage and severe hyperkinesis and those with autism were rated as the most stressful. Hyperkinesis and autism both occur in Down syndrome and their families report a similar degree of stress, as recorded by questionnaire. For all families with a retarded child, many of the same...

Hsr Cytogenetics

Neuroblastoma Facts

Interestingly, there appears to be an excess incidence of neuroblastoma in patients with 45,X (Turner) syndrome and perhaps trisomy 13, whereas trisomy 21 (Down syndrome) appears to be associated with a decreased risk for developing neuroblastoma (Satge et al. 2003 Blatt et al. 1997 Satge et al. 1998). pathways for GDNF. J Cell Sci 116 3855-3862 Satge D, Sasco AJ, Carlsen NL, Stiller CA, Rubie H, Hero B et al. (1998) A lack of neuroblastoma in Down syndrome a study from 11 European countries. Cancer Res 58 448-452 Satge D, Moore SW, Stiller CA, Niggli FK, Pritchard-Jones K, Bown N et al. (2003) Abnormal constitutional karyotypes in patients with neuroblastoma a report of four new cases and review of 47 others in the literature. Cancer Genet Cyto-genet 147 89-98 Shojaei-Brosseau T, Chompret A, Abel A, de Vathaire F, Raquin MA, Brugieres L et al (2004) Genetic epidemiology of neu-roblastoma a study of 426 cases at the Institut Gustave-Roussy in France. Pediatr Blood Cancer 42...

Classifying causes

Chromosomal disorders include all mental retardation caused by a proven chromosomal aberration or a clinically obvious chromosomal syndrome such as Down syndrome. However, chromosome analysis should be performed in Down syndrome because translocation, mosaicism, or other abnormalities are found in 5 per cent of cases. Chromosomal anomalies associated with retardation account for up to 40 per cent of severe cases, and 10 to 20 per cent of mild cases. ( ,5,,8.,9and 19


Chromosome mutations involve changes in the structure of a chromosome or the loss or gain of a chromosome. Three types of chromosome mutations are shown in Figure 12-6. A deletion is the loss of a piece of a chromosome due to breakage. In an inversion, a chromosomal segment breaks off, flips around backward, and reattaches. In a translocation, a piece of one chromosome breaks off and reattaches to a nonhomologous chromosome. In nondisjunction (NAHN-dis-JUNGK-shuhn), a chromosome fails to separate from its homologue during meiosis. One gamete receives an extra copy of a chromosome, and another gamete receives no copies. An example of non-disjunction that results in Down syndrome is shown in Figure 12-7. Some chromosome mutations are the loss or gain of entire chromosomes. The mutation that gives a person three copies of chromosome 21 results in Down Syndrome. Some chromosome mutations are the loss or gain of entire chromosomes. The mutation that gives a person three copies of...