Trisomy 21 Ebook

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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Aetiological Classification

The frequent association of ARM with common chromosomal anomalies is well known (e.g. Down syndrome, trisomy 18, 13q-, cat-eye syndrome (CEM), or genetic syndromes such as Currarino syndrome, FG syndrome, VATER association and others 14, 17, 22, 35, 39, 42, 48, 75, 80, 82, 85, 95, 98, 99, 111, 115, 123 . Teratogenic effects of certain agents such as thalidomide, oestrogen and ethanol intake has also been well described 8, 61, 89 . In a study of 1,846 babies with ARM 24 , chromosomal anomalies were found in 11 , the most frequent form being perineal fistula. The frequencies of trisomy 21, 13, and 18 among babies with ARM were 15, 30, and 90 times higher, respectively, in comparison to neonates in the general population (Table 2.3). 2.4.2 Down Syndrome The ARM occurs more frequently with Down syndrome than in the general population and there is a higher rate of deformities without fistula 11, 116 . In a study of 1,992 patients with ARM in Japan 30 , Down syndrome was seen in 101...

In the Twentieth Century

Distal Colostogram

Reports recognizing associated anomalies in other midline structures such as esophageal atresia and tracheoesophageal fistula, duodenal atresia, neural tube defects (tethered cord), vertebral anomalies, sacral anomalies, genitourinary anomalies, and instances of congenital heart disease that accompanied imperforate anus became prominent 19, 30, 41, 51, 103, 117, 118, 147, 171 . Acronyms like VATER and VACTERL describe instances of ARM with many of these associated conditions 41, 51, 74, 78, 131 . Certain genetic abnormalities were noted to coexist with ARM, including instances of trisomy 13-15, 16-18, and 21 (Down syndrome) 41, 43, 165 . The absence of associated rectal fistulae in the latter group also became apparent 43, 165 . ARM were also noted to be associated with the cat-eye syndrome (otic atresia and coloboma), Currarino syndrome (rectal stenosis, sacral anomalies, presacral teratoma, or anterior meningocele) and occasionally Hirschsprung disease 24, 29, 41, 86, 89, 98, 104 ....

Environmental Factors

Zlotogora J, Abu-Dalu K, Lernau O, Sagi M, Voss R, Cohen T (1989) Anorectal malformations and Down syndrome. Am J Med Genet 34 330-331 65. Clarke SA, Van der Avoirt A (1999) Imperforate anus, Hirschsprung's disease, and trisomy 21 a rare combination. J Pediatr Surg 34 1874

From the amyloid protein A4 to isolation of the first Alzheimers disease gene amyloid A4 precursor protein APP

The steadily emerging amyloid hypothesis received perhaps its greatest infusion of support in the early 1980s when Dr. George Glenner, an amyloidologist, entered the scene and argued that amyloid was the central player in AD pathology (Glenner 1981). By the summer of 1983, Glenner and his assistant, Cai'ne Wong, had started obtaining their first amino acid sequences from cerebral blood vessel amyloid isolated from a patient with Down syndrome (Tanzi and Parson 2000). In May, 1984, they published the first sequence of the 4 kDa peptide (called the amyloid p protein), which was found to be the major component of p-amyloid (Glenner and Wong 1984a). In a follow-up paper in August 1984, Glenner and Wong (1984b) showed the same amino acid sequence for amyloid p-protein deposits in both Down syndrome and AD and, since Down syndrome is caused by trisomy 21, made the prophetic statement that a genetic defect causing AD might be localized on chromosome 21. A year later, Colin Masters, who had...

Reasoning Intelligence

A study of mild retardation and Down Syndrome reported by Haier and colleagues in 1995 showed higher brain GMR in both groups compared to matched controls. They speculated that a failure of normal developmental neural pruning could be the basis for a person having too many synaptic connections and redundant brain circuitry resulting in inefficient problem solving, low IQ, and high GMR. Standard score images for each retarded subject revealed considerable heterogeneity of GMR patterns. In the same study, MRI was used to measure brain volume. For the combined samples of mildly retarded, Down Syndrome, and controls, there was an inverse relationship between GMR and IQ and an inverse relationship between GMR and brain volume. There also was a positive relationship between brain size measured by MRI and IQ, consistent with many other studies. Clearly, the use of brain imaging to study complex reasoning in humans has potential for elucidating the biological...

Oxidative Stress From Secondary to Primary Event

Original descriptions of oxidative stress (Martins et al. 1986 Smith et al. 1991) were dismissed as epiphenomena (Mattson et al. 1995), based on the notion that plaques and NFT were long-lived and hence expected to accumulate oxidative damage similar to in other long-lived proteins such as collagen (Monnier and Cerami 1981). Amyloid-P in vitro was found to be toxic via an oxidative mechanism (Yankner et al. 1989), placing oxidative stress as a secondary event. This toxicity in vitro is related to its ability to bind to iron (Schubert and Chevion 1995 Rottkamp et al. 2001). Cell culture studies aside, what happens in vivo Proponents of the longevity notion were somewhat correct long-lived proteins do accumulate oxidative damage. However, the majority of the oxidative damage that is found in AD is short-lived. Indeed, oxidized RNA is markedly increased in neurons in AD (Nunomura et al. 1999) and Down syndrome

Structure Transcripts and Alternative Splicing of the Tau Gene

Hyperphosphorylated, MT-dissociated tau protein is the major component of intracellular neurofibrillary tangles (NFTs), a hallmark of almost all types of neurodegeneration including Alzheimer's disease and the adult dementia that accompanies Down syndrome (Billingsley and Kincaid 1997 Lovestone and Reynolds 1997). NFTs, in the absence of extracellular amyloid deposits, define several neurodegenerative diseases grouped under the term tangle-only tauopathies (Ingram and Spillantini 2002 Sergeant et al. 2005). Among them are progressive supranuclear palsy (PSP), corti-cobasal degeneration (CBD), Pick's disease (PiD), argyrophilic grain disease, and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Hyperphosphorylated tau is also found in patients suffering from myopathies NFTs form in the brains of sufferers from myotonic dystrophy type 1 (DM 1), a pleiotropic disorder whose symptoms include dementia (Modoni et al. 2004 Sergeant et al. 2001) and NFT-like...

Tau Connection to Disease Epilogue

Skewed ratios of tau isoforms clearly influence the activity and effects of tau besides the well-documented results of altered exon 10 inclusion, excess inclusion of exons 2 and 3 causes gliopathy and spinal cord degeneration (Higuchi et al. 2002) and tau is cleaved to its N-terminal fragment very early in neuronal apoptosis, in turn becoming an effector of the process (Canu et al. 1998 Fasulo et al. 2000). Moreover, tau transcription decreases greatly in neuronal cells vulnerable to apoptosis (Esclaire et al. 1998), whereas it increases in sufferers of Down syndrome, who often develop early-onset dementia (Mehta et al. 1999 Oyama et al. 1994).

Should Everyone Be Tested

One fact emerges from this back-of-the-envelope analysis. Until the unit cost of DNA testing drops by a factor of 2-5, it is unlikely that we will see a significant effort to screen millions of young Americans to identify CF carriers. The trump card that could refute this prediction is malpractice litigation. If even a single couple who gave birth to a child with CF successfully sued their physician for failing to alert them to the availability of the carrier test, CF testing would rapidly become widespread. During the late 1970s and early 1980s, lawsuits or fear of them accelerated the pace of prenatal screening for Down syndrome and for spina bifida (see Chapter 8).

Genetics of Cloacal Exstrophy

Cloacal Exstrophy may be a spontaneous error of development that is due to either a somatic mutation or a complex gene-environment interaction 17 . However, within a group of 232 families, 4 multiplex families were identified, suggesting some genetic component in the causation of these anomalies. A single case report of cloacal exstrophy due to an unbalanced translocation between the long arm of chromosome 9 and the long arm of the Y chromosome lends further support to this hypothesis 18 . In a review of 22 cases of cloacal exstrophy, Husmann reported 1 female with trisomy 21 and 1 mosaic (45XO 46XX) 19 .

Ap appears to be a critical component of the pathophysiological cascade that leads to dementia

The observation that all known genetic causes of AD, including PS1, PS2, APP mutations, trisomy 21, and even apoEs4, cause changes in Ap metabolism and elevated plaque deposition leads to the conclusion that Ap is central to the disease process (Selkoe 2000). Yet how Ap disrupts neural function remains uncertain.

Familial AD and Risk Factors

Established genetic factors implicated in AD include mutations in APP (chromosome 21), mutations in presenilin 1 (PS1 chromosome 14) and PS2 (chromosome 1), and the susceptibility allele of ApoE4 (chromosome 19 Price et al. 1998 Hardy 2006a Ghiso and Wisniewski 2004 Bertram and Tanzi 2005). Autosomal dominant mutations in APP, PS1, or PS2 usually cause disease earlier than occurs in sporadic cases, with the maj ority of mutations in APP, PS1 and PS2 influencing BACE1 and y-secretase cleavages of APP to increase the levels of all Ap species or the relative amounts of toxic Ap42 (Ghiso and Wisniewski 2004). Individuals with duplications of APP (Rovelet-Lecrux et al. 2006) or with trisomy 21 (Down's syndrome Hardy 2006a) have an extra copy of APP and develop AD pathology relatively early in life. The presence of ApoE4 predisposes to later onset AD and some cases of late-onset fAD (Bertram and Tanzi 2005 Corder et al. 1994).

Brushfield Spots And Hypotonia

Brushfield Spots Images Trisomy

This infant with Zellweger syndrome had marked hypotonia and shows the typical appearance of the head and face, the single palmar creases, and clinodactyly. There is commonly ulnar deviation with simian creases of the hand. Brushfield's spots also occur in infants with Zellweger syndrome. Because of the hypotonia, craniofacial findings, Brushfield's spots, and simian creases, these infants often are mistaken for infants with trisomy 21. Figure 3.208. This infant with Zellweger syndrome had marked hypotonia and shows the typical appearance of the head and face, the single palmar creases, and clinodactyly. There is commonly ulnar deviation with simian creases of the hand. Brushfield's spots also occur in infants with Zellweger syndrome. Because of the hypotonia, craniofacial findings, Brushfield's spots, and simian creases, these infants often are mistaken for infants with trisomy 21.

Segregation of a missense mutation in the amyloid protein precursor gene with familial Alzheimers disease

Swedish Mutation

It has been known for more than 50 years that families exist in which AD has an early onset (< 60 years) and is inherited as an autosomal dominant trait (Familial Alzheimer's disease (FAD) Lowenberg and Waggoner 1934), but the techniques of molecular genetics only made analysis of these families feasible in the late 1980s. Initial studies of FAD focused on chromosome 21 because individuals with Down Syndrome all develop AD and Ap is derived from a precursor, p-amyloid protein precursor (APP), that is encoded by a gene on chromosome 21 (Goldgaber et al. 1987b Kang et al. 1987 Robakis et al. 1987b Tanzi et al. 1987). However, the APP gene was quickly excluded in several families (Tanzi et al. 1987 Van Broeckhoven et al. 1987). At this time, FAD was assumed to be a homogeneous disorder therefore, exclusion of APP in one family was thought to exclude the gene in all families.

Plantar Crease Is Absent -when

Newborn Ape

This infant with trisomy 21 has a single palmar crease. There is no clinodactyly but there is hypoplasia of the middle phalanx of the fifth finger as noted by the decreased distance between the finger creases. The single palmar crease is seen in about 45 of infants with trisomy 21 and is a finding in many other syndromes. Figure 4.54. This infant with trisomy 21 has clinodactyly but normal palmar creases. Clinodactyly with an absent or hypoplastic middle phalanx of the fifth finger is present in about 50 of infants with trisomy 21. Figure 4.55. The gap between the first and second toes (sandal or thong sign) is a typical finding in trisomy 21. The feet are broad and short. The plantar surfaces are creased with a deep long furrow (ape-line) between the first and second toes.

Intracranial Calcification

Intracranial Calcification Torch

Dysplasia, Fahr syndrome,Down syndrome, tuberous sclerosis, pseudo-TORCH syndrome, Aicardi-Gou-tieres syndrome, Kearns-Sayre syndrome, carbonic anhydrase II deficiency, and COFS syndrome (Linna et al. 1982). CT scanning reveals calcium deposition in the basal ganglia (striatum and pallidum) in about 50 of patients with Cockayne syndrome (Jin et al. 1979 Houston et al. 1982). The dentate nuclei of the cerebellum and the cortex of the brain are also frequently involved. Microcephaly and patchy demyeli-nation, often severe, of the subcortical white matter are additional neuropathologic findings (Gorlin et al.

Distended Veins In Scalp

Scalp Vein

Extreme hypotonia in a term infant who appears to slip through die hands of her examiner when held upright under the arms. Most term newborns can maintain the head in the same plane as the trunk when lifted by the arms or ventrally suspended. Extreme head lag is a sign of hypotonia that can be seen in infants with Down syndrome, prematurity, or brain damage.

Chromosomal Disorders

Wolf Hirschhorn

Chromosomal abnormalities are fairly common. They occur in about 1 in every 200 deliveries, although many of these infants are phenotypically normal. In addition, 50 of all spontaneous abortions involve a chromosomal abnormality. Nondisjunction, where an extra chromosome (or part of a chromosome) is present (e.g., trisomy 21), is the most common cause of chromosomal disorders. Translocation syndromes, where chromosomal material breaks off from one chromosome and translocates to another, may not have classic clinical findings and may be difficult to diagnose. Usually infants with balanced translocations are only carriers and do not demonstrate clinical manifestations, while unbalanced translocations result in clinical signs. A deletion occurs when chromosomal material is missing from either the upper (p) or lower (q) arms of a chromosome (e.g., cri du chat syndrome with deletion of the upper short arm of chromosome 5 5p-). An abnormal number of X or Y chromosomes can also result in...

Musculoskeletal Disorders

Microcephalic Newborns

Chest radiograph showing 11 ribs. The presence of 11 ribs is not an uncommon finding in normal infants but occurs with greater frequency in infants with Down syndrome. Note the cardiac enlargement and enlarged thymus. Figure 1.1. Chest radiograph showing 11 ribs. The presence of 11 ribs is not an uncommon finding in normal infants but occurs with greater frequency in infants with Down syndrome. Note the cardiac enlargement and enlarged thymus.

Robinow Syndrome Type

Nursing Diagnosis Feet

The typical appearance of an infant with trisomy 21 (Down syndrome). Note die marked hypotonia, flat facies, single palmar crease and separation of the first and second toes. The abdominal surgery was for the common finding of duodenal atresia. There is a burn at the left knee which occurred during surgery. The incidence of trisomy 21 is 1 in 700 newborns. The typical findings in trisomy 21 include hypotonia, poor Moro's reflex, hyperflexibility of joints, excess skin at the back of the neck, a flat facial profile, slanted palpebral fissures, dysplasia of the pelvis, and hand and feet abnormalities. Figure 4.40. The typical appearance of an infant with trisomy 21 (Down syndrome). Note die marked hypotonia, flat facies, single palmar crease and separation of the first and second toes. The abdominal surgery was for the common finding of duodenal atresia. There is a burn at the left knee which occurred during surgery. The incidence of trisomy 21 is 1 in 700 newborns. The...

Genetics molecular biology and animal modeling of Alzheimers disease

Christine Van Broeckhoven

Our group at the Center for Research in Neurodegenerative Disease, at the University of Toronto, first became interested in several aspects of the biology of Alzheimer's disease (AD) during the early 1980s. The relative homogeneity of the clinical and neuropathological features of (AD) had led to the prevailing assumption that AD was likely to be a single homogeneous disorder. At that time, standard biochemical methods were being applied to dissect the protein composition of both the amyloid plaque and the neurofibrillary tangle (NFT). While these biochemical studies were on the edge of providing important clues to the biochemical pathogenesis of AD, mechanistic insights into the disease remained elusive. One notable exception was the observation that AD clustered in some families and was often inherited as an autosomal dominant trait. This observation alone, however, was insufficient to provide much traction. Indeed, some early attempts to define the chromosomal location of the...

Do Mutations Cause Crime

Testicular Atrophy Picture

In 1958, the French geneticist, Jerome Lejeune, discovered that persons with Down syndrome had 47 chromosomes (the normal complement plus an extra number 21), thus confirming a hypothesis about the cause of Down syndrome that had been proposed nearly 30 years earlier. This extremely important discovery triggered huge interest among other scientists. Over the next few years, other researchers made rapid progress in finding abnormal numbers of chromosomes and associating them with physical or mental abnormalities. But no one was prepared for Dr. Jacobs' report.

Can We Improve the Gene Pool

In the United States and Europe, a new and more subtle form of negative eugenics may be emerging. It is technologically enabled, physician supported, and widely embraced by consumers. Simply put, a significant fraction of women, when offered testing that could lead them to avoid the birth of children with serious genetic or congenital disorders, choose to be tested and to abort affected fetuses. Amniocentesis and fetal chromosome analysis became widely available in the 1970s. About 300,000 pregnant women (most 35 and older) in the United States now undergo this test each year. About 1,000 will discover that they are carrying a fetus with Down syndrome, and three-quarters of them will obtain an abortion. About 3 out of 4 of all pregnant women (that is about 3,000,000 women) will, regardless of age, undergo a screening test to see if the fetus may have spina bifida. About 3,000 will eventually discover that they are carrying an affected fetus, and about three-quarters of them will abort.

No Manifest Opening

High and intermediate varieties of anorectal agenesis without fistula are more common in our series and in the Japanese series than in other series. Some of our colleagues have seen this anomaly in association with Down syndrome (R. Chadha, 2005, personal communication). The coexistence of a proximal atresia has been described by Ein 25 , Gangopadhyaya et al. 28 , Sharma et al. 65 , and Rajendran and Varma 54 (Fig. 15.8).

Background

In addition to this project, I did not give up further characterizing polyclonal antibodies to PHF. Nobuyuki Nukina, a senior resident in neurology, took an entirely different approach. Following a report on the purification of so-called SAF (scrapie-associated filaments), he prepared Sarkosyl-insoluble fractions from AD brains and digested a PHF-enriched fraction with proteinase K (Diringer et al. 1983). Unexpectedly, the digested material provided a ladder pattern of anti-PHF-reactive bands. The smallest and strongest band was at about 10 kDa (Nukina and Ihara 1985). This was the first time I saw a distinct anti-PHF-reactive band. Soon after, using a neonatal (three-month-old) Down syndrome brain, Nobuyuki went further and found a distinctly labeled (although somewhat broad) band at about 50 kDa on the blot of the soluble fraction. He quickly confirmed that this strong reactivity was not confined to Down syndrome brain but was a feature of fetal or neonatal brain. Thus, fetal brains...

Molecular Biology

The discovery of GCIs in MSA brains firmly established glial pathology as a biological hallmark of this disorder, akin to the LB of PD. GCIs are argyrophilic and half moon, oval, or conical in shape (Lantos, 1998 Papp et al., 1989). They consist of 20 to 30 nm diameter filaments and contain the classical cytoskeletal antigens, ubiquitin and tau (Lantos, 1998 Cairns et al., 1997a). Furthermore, a-synuclein, a presynaptic protein which is affected by point mutations in some families with autosomal dominant PD (Goedert and Spillantini, 1998) and which is present in LBs (Spillantini et al., 1997), has also been observed in both neuronal and glial cytoplasmic inclusions (Wakabayashi et al., 1998c Arima et al., 1998 Tu et al., 1998) in brains of patients with MSA. The accumulation of a-synuclein into filamentous inclusions appears to play a mechanistic role in the patho-genesis of several a-synucleinopathies including PD, dementia with LBs, Down syndrome, familial AD, sporadic AD, MSA, and...

Pathology

The accumulation of a-synuclein into filamentous inclusions appears to play a key role not only in MSA, but also in a growing number of a-synucleinopathies such as PD, dementia with Lbs (DLB), Down syndrome, familial Alzheimer's disease (AD), and sporadic AD (153). The a-synuclein accumulation in GCIs as well as in neuronal inclusions associated with MSA precedes their ubiquitination (154). Importantly, a-synuclein, but not ubiquitin, antibodies also reveal numerous degenerating neurites in the white matter of MSA cases (154). This suggests that an as yet unrecognised degree of pathology may be present in the axons of MSA cases, although whether neuronal axonal a-synuclein pathology precedes glial a-synuclein pathology has not been examined.

Discussion

Studies performed two decades later, particularly those by Nathan Malamud, established that AD changes in DS were seen in all individuals beyond the age of 40 (Malamud 1972). Moreover, the AD neuropathology in DS was unique to trisomy 21, as it was not seen in mental retardation in general without DS. In the 1970s, the similarity of AD pathology was extended to the ultrastructural level (Burger and Vogel 1973). Therefore, even before the recognition of AD as the most common neurodegenerative disorder with a high prevalence in the mid-1970s, it was well established that the neu-ropathology of AD was fully recapitulated in older DS individuals. Indeed, Malamud and Hirano suggested that the chromosomal abnormalities in Down's syndrome might predispose to development of the neuropathologic changes characteristic of Alzheimer's disease (Malamud and Hirano 1974). The next important milestone was the sequencing of the amyloid protein in meningeal vessels of adults with DS by Glenner in the...

Atypical Karyotypes

The high risk of AD in DS is also associated with early mortality, with an average life expectancy at birth of only 56 years (Baird and Sadovnick,1988). Karyotypic analysis of adults aged over 70 years with DS can provide an opportunity to identify genetic factors associated with longevity. While these cases are rare, they are highly informative and suggest that karyotypes that decrease pAPP load are associated with improved survival and reduced risk of AD. Prasher and colleagues determined the clinical and molecular correlates of partial trisomy 21 in a 78-year-old woman with DS 46,XX,rec(21)dup q, inv(21) (p12q22.1) (Prasher et al., 1998). Although she did not display the full range of stigmata associated with the DS phenotype, she developed several of the characteristic age-related medical conditions, including hypothyroidism, cataracts, hypotonia, and hearing impairment. Analysis of gene sequences on chromosome 21 using fluorescent in situ hybridization showed that the partial...

Newborn Neck Webbing

Jarcho Levin Syndrome

A short neck may result from absence, malformation or coalescence of one or more cervical vertebrae, often giving the impression that the head is resting directly on the shoulders (Klippel-Feil syndrome, Jarcho-Levin syndrome). Neck webbing or high placement of the scapulae can give a similar appearance (Turner's syndrome, Down syndrome, cleidocranial dysostosis).

Turner Syndrome

Turner Syndrome Infant

The gap between the first and second toes (sandal or thong sign) is a typical finding in trisomy 21. The feet are broad and short. The plantar surfaces are creased with a deep long furrow (ape-line) between the first and second toes. Figure 4.56. A close-up view of the broad short foot of an infant with trisomy 21 shows the marked separation of the first and second toes and the deep furrows on the sole. Figure 4.56. A close-up view of the broad short foot of an infant with trisomy 21 shows the marked separation of the first and second toes and the deep furrows on the sole. Figure 4.57. Total radiograph of an infant with trisomy 21 shows the long narrow chest cage with downslanting ribs due to hypotonia. Any infant who is hypotonic has this appearance of the chest cage. The finding of eleven pairs of ribs, as in this infant, is common in Down syndrome but also may occur as a finding in normal infants. The pelvis is a typical mongoloid pelvis. The infant also had congenital...

Are You at High Risk

French Anderson

Interest in the use of molecular markers to find genes that predisposed to Alzheimer disease received great impetus from the stunning success in 1983 of a team led by Jim Gusella, a molecular biologist at the Massachusetts General Hospital, in mapping the gene for Huntington disease, another neurodegenerative disease, to a tiny region on the tip of chromosome 4. At the time, efforts to map disease genes by showing they must be located near established DNA markers seemed quixotic. Given the vast size of the human genome, no one thought that Gusella and his colleagues had a chance. What had seemed impossible suddenly appeared possible. When they quickly succeeded, the whole scientific world took notice. A physician-scientist named Peter St. George-Hyslop quickly took up the challenge to repeat Gusella's feat with Alzheimer disease. He arranged with Gusella to do postdoctoral studies in his laboratory so he could learn to do linkage studies. Long intrigued by the observation that...

Conclusions

The DSM-IV classification of maladaptive levels of intelligence is also a useful model because it illustrates how categorical and dimensional diagnoses are not necessarily mutually exclusive. There are instances of mental retardation that have specific etiologies. Recognizing that psychopathology is generally best classified along continuous distributions does not imply that no instances of qualitatively distinct conditions would not exist or could not be recognized. On the other hand, the categorical diagnoses in the case of mental retardation are generally placed on Axis III as physical disorders (e.g., Down syndrome) that can be traced to a specific biological event (i.e., trisomy 21), and the mental retardation of persons with these categorically distinct disorders is still described well in terms of the continuously distributed cognitive impairments. A general factor of intelligence (ability to reason, plan, solve, learn, and comprehend information) saturates most to all measures...