Disorders

ADHD
Attention-deficit/hyperactivity disorder is characterized by persistent patterns of inattention or hyperactivity-impulsivity (or both) that are more severe or more frequent than would be expected from the patient’s developmental level. Some features must have been present before the age of 7 years (although the diagnosis may have been made by then).

Diagnostic criteria

DSM-IV criteria
DSM-IV subdivides attention-deficit/hyperactivity disorder into three types:
· combined type;
· predominantly inattentive type;
· predominantly hyperactive-impulsive type.
For each of these types, the following diagnostic criteria must be met:
· some symptoms of hyperactivity-impulsivity or inattention were present and caused impairment before the age of 7 years;
· the symptoms cause impairment in at least two settings (e.g. school or work and home);
· there is clear evidence of significant social, academic or occupational impairment;
· the symptoms do not occur only during the course of pervasive developmental disorder, schizophrenia or another psychotic disorder, and they are not better accounted for by another mental disorder.
The type of attention-deficit/hyperactivity disorder is defined by the following criteria:
· in the combined type, both criteria A1 and A2 (which follow) have been met in the past 6 months;
· in the predominantly inattentive type, criterion A1 has been met for the past 6 months but criterion A2 has not;
· in the predominantly hyperactive-impulsive type, criterion A2 has been met for the past 6 months but criterion A1 has not.

Criterion A1 (criteria for inattention)
Criterion A1 states that at least six of the following must have been present for at least 6 months to a maladaptive degree that is inconsistent with the development level of the patient:
· often fails to give close attention to details or makes careless mistakes in schoolwork, work or other activities;
· often has difficulty sustaining attention in tasks or play;
· often seems not to listen when spoken to directly;
· often does not follow through on instructions and fails to finish schoolwork, tasks or workplace duties;
· often has difficulty organizing tasks and activities;
· often avoids or dislikes or is reluctant to engage in tasks that require sustained mental effort;
· often loses things that are necessary for tasks or activities;
· often easily distracted by extraneous stimuli;
· often forgetful in daily activities.

Criterion A2 (criteria hyperactivity-impulsivity)
Criterion A2 states that at least six of the following must have been present for at least 6 months to a maladaptive degree that is inconsistent with the development level of the patient.
The hyperactivity criteria are:
· often fidgets with hands or feet or squirms when sitting;
· often leaves seat in classroom or at other times when remaining seated is expected;
· often runs about inappropriately or climbs excessively (in adults, this feature may be limited to feelings of restlessness);
· often has difficulty playing or engaging in leisure activities quietly;
· often `on the go’ or often acts as if `driven by a motor’
· often talks excessively.
The impulsivity criteria are:
· often blurts out answers before questions have been completed;
· often has difficulty awaiting turn;
· often interrupts or intrudes on others.

ICD-10 criteria
ICD-10 defines the same disorder as `disturbance of activity and attention’, one of the `hyperkinetic disorders’.
The ICD-10 criteria are almost identical to the DSM-IV criteria in the items listed. However, ICD-10 has more stringent requirements as to the number and types of criteria that must be present for the diagnosis to be made – it requires at least six of the inattention items, at least three of the hyperactivity items and at least one of the impulsivity items.
ICD-10 also subdivides the disorder differently, depending on whether conduct disorder is also present.

Symptoms and Signs

It is usual for parents to have observed excessive motor activity when the patient was a toddler, often when the child first began to crawl or walk. The pattern of clinical features largely depends on the age of the patient. The disorder should be described as being of the predominantly inattentive type, the predominantly hyperactive-impulsive type or the combined type on the basis of the features for the past 6 months; it is possible for patients to change between types.
In preschool children, the following may be seen:
· temper tantrums;
· argumentative behavior;
· aggression;
· fearlessness (which often leads to frequent accidental injury);
· boisterous behavior;
· sleep problems.
In school-age children, the following may be seen:
· difficulties at school;
· poor peer relationships;
· development of comorbid disorders (e.g. conduct disorder, oppositional defiant disorder, Tourette syndrome, mood disorders, anxiety disorders).
In adolescents, the following may be seen:
· an internal sense of restlessness, as described by the patient;
· failure to complete independent academic work;
· poorly organized approaches to school and work;
· poor follow-through on tasks;
· risk-taking behaviors.

Prognosis

The clinical features often abate to a greater or lesser extent in late adolescence and adulthood. However, the individual prognosis varies:
· 20-30% of children with attention-deficit/hyperactivity syndrome do not manifest any symptoms as young adults;
· 60-70% of children with attention-deficit/hyperactivity syndrome continue to be troubled by at least one of the disabling core symptoms as young adults;
· 30% of children with attention-deficit/hyperactivity syndrome meet the criteria for the full syndrome at 18 years of age;
· 20-30% of children with attention-deficit/hyperactivity syndrome develop more serious psychopathology, such as substance abuse and antisocial personality disorder.

Angelman Syndrome
In 1965, Dr. Harry Angelman, an English physician, first described three children with characteristics now known as the Angelman syndrome (AS) (1). He noted that all had a stiff, jerky gait, absent speech, excessive laughter and seizures. Other cases were eventually published (2-8) but the condition was considered to be extremely rare and many physicians doubted its existence. The first reports from North America appeared in the early 1980s (9, 10) and within the last ten years many new reports have appeared (11-18). Dr. Angelman relates the following regarding his discovery of this syndrome (19).

“The history of medicine is full of interesting stories about the discovery of illnesses. The saga of Angelman’s syndrome is one such story. It was purely by chance that nearly thirty years ago three handicapped children were admitted at various times to my children’s ward in England. They had a variety of disabilities and although, at first sight, they seemed to be suffering from different conditions, I felt that there was a common cause for their illness. The diagnosis was purely a clinical one because, in spite of technical investigations which today are more refined, I was unable to establish scientific proof that the three children all had the same handicap. In view of this I hesitated to write about them in the medical journals. However, when on holiday in Italy I happened to see an oil painting in the Castelvecchio museum in Verona called . . . a Boy with a Puppet. The boy’s laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children. It was not a name that pleased all parents but it served as a means of combining the three little patients into a single group. Later the name was changed to Angelman syndrome. This article was published in 1965, and after some initial interest, lay almost forgotten until the early eighties.”

AS has been reported throughout the world among divergent racial groups. In North America, the great majority of known cases seem to be of Caucasian origin. Although the exact incidence of AS is unknown, an estimate of between 1 in 15,000 to 1 in 30,000 seems reasonable (16, 20).

Developmental and Physical Features
Angelman syndrome is usually not recognized at birth or in infancy since the developmental problems are nonspecific during this time. Parents may first suspect the diagnosis after reading about AS or meeting a child with the condition. The most common age of diagnosis is between three and seven years when the characteristic behaviors and features become most evident. A summary of the developmental and physical findings has recently been published (21) for the purpose of establishing clinical criteria for the diagnosis and these are listed below. All of the features do not need to be present for the diagnosis to be made, and the diagnosis is often first suspected when the typical behaviors are recognized.
Developmental History and Laboratory Findings
· Normal prenatal and birth history with normal head circumference; absence of major birth defects
· Developmental delay evident by 6 – 12 months of age
· Delayed but forward progression of development (no loss of skills)
· Normal metabolic, hematologic and chemical laboratory profiles
· Structurally normal brain using MRI or CT (may have mild cortical atrophy or dysmyelination)

Consensus Criteria for Clinical Features in Angelman Syndrome
Consistent (100%)
· Developmental delay, functionally severe
· Speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
· Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs
· Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span
Frequent (more than 80%)
· Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2
· Seizures, onset usually < 3 years of age
· Abnormal EEG, characteristic pattern with large amplitude slow-spike waves
Associated (20 – 80%)
· Strabismus
· Hypopigmented skin and eyes
· Tongue thrusting; suck/swallowing disorders
· Hyperactive tendon reflexes
· Feeding problems during infancy
· Uplifted, flexed arms during walking
· Prominent mandible
· Increased sensitivity to heat
· Wide mouth, wide-spaced teeth
· Sleep disturbance
· Frequent drooling, protruding tongue
· Attraction to/fascination with water
· Excessive chewing/mouthing behaviors
· Flat back of head

Genetic basis of AS
For several decades the chromosome study of AS individuals revealed no abnormalities, but with the development of improved methods a very small deleted area was found in chromosome 15. Molecular methods such as FISH (fluorescence in situ hybridization) now demonstrate a deletion in about 70% of individuals with AS. The deleted area, although extremely small, is actually quite large when viewed at the molecular level. It is believed to be about 4 million base pairs in length, enough to contain many genes.
The deleted region on chromosome 15 is known to contain genes that are activated or inactivated depending upon the chromosome’s parent of origin (i.e., a gene may be turned on on the chromosome 15 inherited from the mother but off on the chromosome 15 inherited from the father). This parent-specific gene activation is referred to as genetic imprinting. Because the deletions seen in AS only occur on the chromosome 15 inherited from the mother, the gene(s) responsible for AS were predicted to be active only on the maternal chromosome 15. Disruption of genes that are active on the paternally-derived chromosome 15 is now known to cause another developmental disorder termed the Prader-Willi syndrome (PWS). The PWS gene(s) are actually located close to the AS gene, but they are different.

In 1997, a gene within the AS deletion region called UBE3A was found to be mutated in approximately 5% of AS individuals (22, 23). These mutations can be as small as 1 base pair. This gene encodes a protein called a ubiquitin protein ligase, and UBE3A is believed to be the causative gene in AS. All mechanisms known to cause AS appear to cause inactivation or absence of this gene. UBE3A is an enzymatic component of a complex protein degradation system termed the ubiquitin-proteasome pathway. This pathway is located in the cytoplasm of all cells. The pathway involves a small protein molecule, ubiquitin, that can be attached to proteins thereby causing them to be degraded (24). In the normal brain, the copy of UBE3A inherited from the father is almost completely inactive, so the maternal copy performs most of the UBE3A function in the brain. Inheritance of a UBE3A mutation from the mother causes AS; inheritance of a UBE3A mutation from the father has no detectable effect on the child. In some families, AS caused by a UBE3A mutation can recur in more than one family member.

Another cause of AS (2-3% of cases) is paternal uniparental disomy (UPD), where the child inherits both copies of chromosome 15 from the father, with no copy inherited from the mother. In this case, there is no deletion or mutation, but the child is still missing the active UBE3A gene because the paternal-derived chromosomes only have brain-inactivated UBE3A genes.

A fourth class of AS individuals (3-5% of cases) have inherited chromosome 15 copies from both mother and father, but the copy inherited from the mother functions in the same way that a paternal chromosome 15 should function. This is referred to as an “imprinting defect”. Some AS individuals with imprinting defects have very small deletions of a region called the Imprinting Center (IC) (25, 26). The IC regulates the activity of UBE3A from a distant location, but how this regulation occurs is not known. In some cases, AS caused by imprinting defects can recur in more than one member of a family.
These discoveries have led to the realization that there are several genetic “classes” or mechanisms that can cause AS (25, 27). All of these mechanisms lead to the typical clinical features of AS, although minor differences may occur between and within groups. These mechanisms are depicted on the diagram and summarized in the table.

www.angelman.org

Aspergers ……
Asperger’s disorder is a life-long disorder that is usually first diagnosed in childhood and that is characterized by severe impairment in reciprocal social interaction and restricted and repetitive patterns of behavior and interests.

Diagnostic criteria
According to DSM-IV, Asperger’s disorder involves qualitative impairment in social interaction, manifested by at least two of:
· marked impairment in the use of multiple non-verbal behaviors (e.g. eye-to-eye gaze, facial expression, postures and gestures);
· failure to develop relationships with peers at an appropriate developmental level;
· lack of spontaneous seeking to share enjoyment with other people;
· lack of social or emotional reciprocity.
In addition, there must be repetitive and stereotyped patterns of behavior and interests, manifested by at least one of:
· an encompassing preoccupation with at least one stereotyped and restricted interest that is abnormal in itself or abnormal in intensity;
· an inflexible adherence to specific and non-functional routines;
· stereotyped and repetitive motor mannerisms;
· a persistent preoccupation with parts of objects.
The disturbance must cause significant functional impairment, and it must occur in the absence of both significant language delay and significant delay in cognitive development.
Finally, the criteria for another specific pervasive developmental disorder or for schizophrenia must not be met.
The ICD-10 criteria for Asperger’s syndrome are similar in all important respects to the DSM-IV criteria for Asperger’s disorder.

Symptoms and signs
The main clinical features of Asperger’s disorder are:
· a significant impairment in reciprocal social interactions (e.g. a lack of interest in peer relations in individuals aged 3 years and older, a lack of appreciation of social cues and conventions, poor understanding and use of non-verbal social cues, socially inappropriate behaviors, gaze avoidance);
· a significantly restricted repertoire of activities, interests and behaviors (e.g. an obsession with complex specific topics such as sports statistics, ritualized patterns of daily behaviors and exclusion of other activities);
· relatively normal language development in the first 2 years of life – language is lucid with good grammar appropriate to the age of the patient, although it may be stiff, formal, pedantic or repetitive, or have odd prosody or other unusual characteristics; in conversation, patients may pursue a topic of interest to themselves despite social cues from others to change the subject.
· self-help skills and general adaptive behavior (apart from social interaction) that are appropriate to the age of the patient;
· impulsive aggressive behavior;
· mild clumsiness or awkwardness;
· poor visual-motor or visual-spatial skills compared with verbal skills.
Prognosis
Asperger’s disorder is a life-long condition. The prognosis is variable, but people with Asperger’s disorder may learn ways of responding more appropriately to verbal and social cues. Many adults with the disorder are able to lead self-sufficient lives, although they may be considered `odd’.

Autism ……
DSM-IV Criteria

* 299.00 Autistic Disorder

A. A total of six (or more) items from (1), (2), and (3), with at least two from (1), and
one each from (2) and (3):

(1) Qualitative impairment in social interaction, as manifested by at least two of the
following:

(a) Marked impairment in the use of multiple nonverbal behaviors, such as eye-to- eye gaze, facial expression, body postures, and gestures to regulate social interaction
(b) Failure to develop peer relationships appropriate to developmental level
(c) A lack of spontaneous seeking to share enjoyment, interests, or achievements with
other people (e.g., by a lack of showing, bringing, or pointing out objects of
interest)
(d) Lack of social or emotional reciprocity

(2) Qualitative impairments in communication, as manifested by at least one of the
following:

(a) Delay in, or total lack of, the development of spoken language (not
accompanied by an attempt to compensate through alternative modes of
communication such as gesture or mime)
(b) In individuals with adequate speech, marked impairment in the ability to initiate
or sustain a conversation with others
(c) Stereotyped and repetitive use of language or idiosyncratic language
(d) Lack of varied, spontaneous make-believe play or social imitative play
appropriate to developmental level

(3) Restricted, repetitive, and stereotyped patterns of behavior, interests, and activities
as manifested by at least one of the following:

(a) Encompassing preoccupation with one or more stereotyped and restricted
patterns of interest that is abnormal either in intensity or focus
(b) Apparently inflexible adherence to specific, nonfunctional routines or rituals
(c) Stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or
twisting or complex whole-body movements)
(d) Persistent preoccupation with parts of objects

B. Delays or abnormal functioning in at least one of the following areas, with onset
prior to age 3 years: (1) social interaction, (2) language as used in social
communication, or (3) symbolic or imaginative play.

C. The disturbance is not better accounted for by Rett’s disorder or childhood
disintegrative disorder.

Diagnostic and Statistical Manual, 4th Edition, ©1994, American Psychiatric Association

Definition:
Autism is a severe disorder characterized by abnormalities in social functioning language and communication and by unusual interests (Prizant, 1996). The disorder affects every aspect of the child’s interaction of his or her world involves many parts of the brain and undermines the very traits that make us human (Sigman and Ungerer, 1984). Autism is a spectrum disorder which means that its symptoms are expressed in many combinations and any degree if severity (Davis, Fennoy, Laraque, & Kanem, 1992).

Core Characteristics

A. Prevalence
Autism is a rare disorder affecting approximately 4-5 children per 10, 000 with some estimates running as high as 15-20 (Bolton, MacDonald, Pickels, Rios, Goode, Crowson, Bailey, Rutter 1994). Autism is found in all social classes and in every country in which it has it has been sought. It is 3-4 times more common in boys then girls. The greater number of boys appears in groups with IQ’s in the normal range. When girls are affected they tend to be more cognitively impaired (Bolton et al., 1994).

Prognosis
There is no real “cure” for autism. Most children with autism show a gradual improvement of their symptoms with age even though they continue to experience many problems. In early studies describing outcomes for children with autism who received limited help, only 1% to 2% of them became normal in the sense of being indistinguishable from others. About 10% had good outcomes, meaning that they achieved near,-normal functioning in their social behavior and language, progressed in school or work, but continued to display oddities of speech or personality. Another 20% had fair outcomes, making social and educational gains despite significant handicaps that did not permit them to lead an independent existence (Lotter, 1978). Notably the two strongest predictors of adult outcomes in children with autism are IQ and language development.

Social Impairments
Children with autism experience profound difficulties in relating to other people (Bolton, MacDonald, Pickels, Rios, Goode, Crowson, Bailey, Rutter 1994). As they grow older children with autism initiate few social behaviors and seem unresponsive to other people’s feelings (Weeks & Hobson, 1987). Children with autism generally have great difficulty integrating social, communicative, and emotional behaviors, as would be required when greeting a familiar person who enters the room. (Baron-Cohen, Laa, & Riviere, 1995).

Children with autism display impairments in all aspects of social attention, which is the ability to coordinate one’s focus of attention on another person and an object of mutual interest (Joliffe & Cohen Baron, 1997).

Most children with autism respond differently to their care-givers than to unfamiliar adults (Joliffe et al., 1997). The proportion of children with autism who display a secure attachment is 40-50%, slightly lower than that of the normal population. Children with autism also display impairment in emotional understanding, such as information involved in body language, gestures, facial expressions, and prosody (Weeks et al., 1987).

Communication Impairments:
Children with autism display serious abnormalities in communication and language that appear early in life and persist overtime (Davis et al, 1992). One of the first signs of language impairment is their inconsistency in using early preverbal communication, such as proto-imperative, expressions of needs and proto-declarative gestures, direction of another’s attention (Prizant, 1996). Children with autism display several characteristic forms of abnormal speech. For example, common in this population are pronoun reversals, echolalic speech, perseverative speech, and a lack of understanding of pragmatics, or the social understanding of speech (Hardman, Drew & Egan, 1996).

Repetitive Interests and Behaviors:
Children with autism often display narrow patterns of interest, and seem driven to engage in and maintain those interests and behaviors associated with them (Bee, 1998). Children with autism also tend to display self-stimulatory behaviors, such as hand flapping, pencil spinning, singing, head banging, or oral-motor stimulation (Bee, 1997). The purpose of these behaviors is speculated to originate from a lack of attentional control, whereby the child with autism is unable to attend to only certain aspects of their environment ( Bee, 1997; Courchesne, Chisum & Townsend 1995). This influx of stimulation proves to be overwhelming to the child, and these behaviors compensate by providing focus on a narrow range of stimulation

Cognitive Functioning:
About 80% of children with autism also have mental retardation, with approximately 60% having IQ’s less than 50, and 20% having IQ’s between 50 and 70 (Barth, Fein & Waterhouse, 1995). Splinter skills and savantism are sometimes seen in this population. However, their frequency (25% for islets of ability and 5% for savantism) is rare (Barth et al., 1995).

Sensory and Perceptual Impairments:
Sensory abnormalities include over sensitiveness or under sensitiveness to stimulation, over selectiveness and impaired shifting of attention to sensory input, and impairments in cross-modal sensory integration (Klinger & Dawson, 1995).

Cerebral Palsy(CP)
Cerebral palsy (CP) is a neurological disorder affecting body movement and muscle coordination. CP is typically caused by an injury to the brain before, during, or shortly after birth. (However, it is also used as an umbrella term to describe disorders which impair the control of movement resulting from faulty development of areas of the brain.) When the brain injury occurs while the baby is still in the womb (80% of reported cases), it is difficult to explain what caused the problem. It may be caused by abnormal fetal brain development, an infection, an accident in which the mother was injured, a medical condition that the mother had during pregnancy, such as high blood pressure or diabetes, or unknown biochemical or genetic factors. If the injury occurs during birth (10% of reported cases), it is usually due to a deprivation of oxygen or an injury upon having a difficult delivery. Last, if the injury occurs after birth (10% of reported cases), it may be due to a baby being born prematurely, where his or her body is not ready to survive outside the mother’s womb, an infection, an accident where the baby is injured (i.e., motor vehicle), or bleeding in the brain. Approximately 1 in every 1,000 infants have some form of CP.
CP was first described in the 1860′s by an English physician named William Little. He wrote about children who were stiff, had spastic muscles (more so in the legs than arms), and had difficulty grasping objects, crawling, and walking. The condition was called Little’s disease, however, he was describing what is now known as spastic diplegia cerebral palsy.

Features and Characteristics
Children with CP have the inability to control their muscle coordination. Depending on where the damage to their brain occurred, they may have muscle tone that is too tight, too loose, or a combination of both. In addition, some children may have abnormal sensation and perception; impaired sight, hearing or speech, seizures, mental retardation, feeding difficulties, learning disabilities, bladder and bowel control, and difficulty breathing due to postural difficulties. There are four different types of cerebral palsy:

Spastic Cerebral Palsy
If the muscle tone is too high or too tight, the individual has spastic CP. Children with spastic CP often have stiff and jerky movements due to their tone. They often have a hard time moving from one position to another, and often times have difficulty letting go of an object with their hand. Spastic CP is the most common type; approximately 50% of individuals with CP have spastic CP.
Ataxic Cerebral Palsy

When the individual has low muscle tone and poor coordination of movement, they are described as having ataxic CP. Children who are ataxic, look shaky (tremor-like) when trying to perform a task. They often have poor balance and may be very unsteady when they walk.

Athetoid Cerebral Palsy
Athetoid CP is used to describe the individual who has both low and high tone. Children with this type of CP have difficulty holding themselves upright or steady for sitting or walking and have involuntary movements in their arms, upper bodies, and face. Because of these movements, it takes a lot of hard work and concentration to reach for an object. In addition, mixed tone causes them to have difficulty holding onto things.

Mixed Cerebral Palsy
This type of CP is used to describe the individual who experiences both low and high tone.
In addition to having the different types of CP, there are also classifications for the areas of the body that the CP affects:

Quadriplegia
This refers to the individual who is affected in all four limbs. Children with quadriplegia have difficulty moving all of their body parts, and often times require a wheelchair for mobility. Due to the problems controlling the muscles in their face and upper body, they may have trouble speaking and eating.
Hemiplegia
This term is used to describe individuals who have CP that affects only one side of their body – either the right arm and leg or the left arm and leg – while the other side functions normally. Children with hemiplegia are able to walk and run, however, may have a slight limp or awkwardness in their gait.

Diplegia
Individuals who have diplegia are only affected in their legs. Walking or running may be difficult for them, however, since their upper body is not affected, they are able to hold themselves upright and have good use of their arms and hands.

Diagnosis
Physicians diagnose CP by looking at the child’s motor skills, medical history, development, and
characteristics described above. The physician will also test reflexes and look for early development of hand preference (babies younger than 12 months generally do not show hand preference). In addition, the physician must also rule out other disorders that can cause movement problems. The doctor must rule out that the disorder is not getting worse, as CP is not progressive. If the child is losing skills, he or she may have a genetic disorder, metabolic disorder, or muscle disease. Many times, a CT-scan, MRI, and a sonogram may be ordered as well to identify brain disorders or areas that are underdeveloped.

www.ucpa.org

www.ninds.nih.gov/healinfo/disorder/cp/cphtr.htm

Fragile X
Fragile X syndrome is an X-linked-recessive defect of the X chromosome that causes a number of mental and physical problems, most notably mental retardation.

Diagnostic Criteria
Neither DSM-IV nor ICD-10 provides diagnostic criteria for fragile X syndrome.

Symptoms and Signs
Males are typically more severely affected than females.
Common mental and behavioral features of fragile X syndrome include:
· mental retardation, which is usually mild to profound in males; among females with the full mutation, about half are mentally retarded or have educational difficulties.
· attentional deficits, hyperactivity, autism or autistic-like behaviors;
· ‘cluttered’ speech or short bursts of repetitive speech;
· anxiety or mood instability.
Common signs of fragile X syndrome include:
· macrocephaly;
· unusual facies (large ears, long face and prognathism);
· crowding of teeth;
· mild connective tissue dysplasia;
· hyperextensible joints;
· mild cutis laxa;
· flat feet;
· mitral valve prolapse or aortic dilatation;
· macro-orchidism;
· ocular anomalies (e.g. pale blue irises, myopia, nystagmus, strabismus).

Prognosis
The life span of patients with fragile X syndrome is normal.
Early somatic growth is often accelerated.
Developmental milestones are delayed but there is no evidence of regression.

Learning Disorder
There are three main types of learning disorder – reading disorder, mathematics disorder and disorder of written expression. These disorders may be defined as achievement in reading, mathematics or writing that is substantially below the level that would be expected for the patient’s chronological age, measured intelligence and education.

Diagnostic Criteria
The DSM-IV diagnostic criteria for the learning disorders state that:

· achievement in the relevant area (reading, mathematics or writing) must be substantially below what would be expected given the patient’s chronological age, measured intelligence and age-appropriate education;
· the under-achievement must significantly interfere with academic achievement or activities of daily living;
· if a sensory deficit is present, the degree under-achievement must be greater than what would usually be associated with it.

The level of achievement must be measured by individually administered, standardized tests.
The ICD-10 criteria for specific reading disorder and specific disorder of arithmetical skills describe essentially the same conditions as the DSM-IV criteria for reading disorder and mathematics disorder, respectively, with the important difference that in the ICD-10 criteria, specific reading disorder takes precedence over specific disorder of arithmetical skills, so that if criteria for both disorders are met only specific reading disorder would be diagnosed (in contrast with the DSM-IV criteria, which permit a dual diagnosis).

ICD-10 includes diagnostic criteria for specific spelling disorder; although spelling difficulties are included in the DSM-IV criteria for disorder of written expression, problems with writing skills in addition to spelling are required for this diagnosis to be made.

Prognosis
None of the learning disorders becomes apparent until sufficient teaching has taken place for the
problems to become noticeable. Children with good intelligence may function well in the early years of school and develop difficulties only as the expected standards of achievement become higher. Reading disorder in particular responds well with appropriate treatment. Less is known about the long-term prognosis of mathematics disorder or disorder of written expression. All three types of learning disorder can persist into adulthood.
Pervasive Developmental Disorders
Pervasive Developmental Disorders is diagnosed using the DSM Diagnostic Statistics Manual. It is not diagnosed medically by a urine, blood, gentic chromosomal or neurological tests. Parental evaluation, observation, langauge and cognitive assessment are used to evalute the child’s current level of functioning.

Prader
Prader-Willi syndrome is a chromosomal disorder caused by a deletion of chromosome 15. It is associated
with mental retardation and behavioral problems.

Diagnostic Criteria

Neither DSM-IV nor ICD-10 (in its classification of mental disorders) includes diagnostic criteria for Prader-Willi syndrome.

Symptoms and Signs
Clinical features of Prader-Willi syndrome include:
· mental retardation, which is mild in 60% of patients and moderate in 30%;
· developmental delay;
· infantile hypotonia, with early feeding difficulties secondary to hypotonia being particularly common;
· self-injurious behavior (e.g. picking at the skin);
· speech delay, articulation problems and hypernasal speech;
· food-related behavior problems (e.g. excessive appetite, absence of satiation, obsession with eating) usually starting in early childhood and often leading to morbid obesity by mid-childhood;
· other behavior problems (e.g. perseveration, poor control of temper), which become more frequent in later childhood;
· high pain threshold;
· short stature of post-natal onset;
· small hands and feet.
· unusual facies, with almond-shaped eyes and upslanting palpebral fissures;
· strabismus;
· hypogonadism – micropenis and cryptorchidism; hypogonadotropism with delayed puberty and infertility;
· hypopigmentation.
· esotropia, myopia.

The following characteristics are most often found in individuals with PWS and are considered diagnostic criteria for the syndrome (Holm et al, Pediatrics 91, 2, 1993):
Major Clinical Findings
· Neonatal and infantile central hypotonia, improving with age
· Feeding problems and poor weight gain in infancy
· Excessive or rapid weight gain between 1 and 6 years of age; central obesity in the absence of intervention
· Distinctive facial features – dolichocephaly in infants, narrow face/bifrontal diameter, almond-shaped eyes, small-appearing mouth with thin upper lip and down-turned corners of mouth
· Hypogonadism – genital hypoplasia, including undescended testes and small penis in males; delayed or incomplete gonadal maturation and delayed pubertal signs after age 16, including scant or no menses in women
· Global developmental delay before age 6; mild to moderate mental retardation or learning problems in older children
· Hyperphagia/food foraging/obsession with food
Minor Clinical Findings
· Decreased fetal movement, infantile lethargy, weak cry
· Characteristic behavior problems – temper tantrums, violent outbursts, obsessive/compulsive behavior; tendency to be argumentative, oppositional, rigid, manipulative, possessive, and stubborn; perseverating, stealing, lying
· Sleep disturbance or sleep apnea
· Short stature for genetic background by age 15
· Hypopigmentation – fair skin and hair compared with family
· Small hands and/or feet for height/age
· Narrow hands with straight ulnar border
· Eye abnormalities (esotropia, myopia)
· Thick, viscous saliva with crusting at corners of the mouth
· Speech articulation defects
· Skin picking
Supportive Findings
· High pain threshold
· Decreased vomiting
· Temperature instability in infancy or altered temperature sensitivity in older children and adults
· Scoliosis or kyphosis (curvature of the spine)
· Early adrenarche (pubic or axillary hair before age 8)
· Osteoporosis (demineralization, or thinning, of the bones)
· Unusual skill with jigsaw puzzles
· Normal neuromuscular studies
Hyperphagia (abnormal increased appetite)
The cause of hyperphagia in individuals with PWS is thought to be the result of a dysfunction in the hypothalamus. Compulsive eating begins before age 6. The urge to eat is physiological and totally overwhelming. The risk of obesity results not only because individuals with PWS have an insatiable appetite, but because they also burn less calories than others due to low muscle mass and inactivity. Unless their diet is carefully controlled, weight gain can be very rapid leading not only to obesity, but to disease and early death as well. Appetite suppressants have not been proven to be effective in individuals with PWS.

Hypotonia

Motor skills are usually 1 to 2 years behind due to the hypotonia. Balance, strength, coordination and motor planning are often affected. Growth hormone treatment may increase motor skills by increasing muscle mass. Physical therapy and occupational therapy may be useful in promoting development in the affected areas. In addition, low tone may cause feeding problems due to an inability to suck, and could, therefore, result in the infant requiring a feeding tube for the first few days or weeks of life.

Speech articulation Defects
Hypotonia can also lead to poor speech skills. The need for speech therapy should be addressed in early infancy. Speech problems can lead to frustration and sometimes aggressive behavior. Products to increase saliva may help articulation skills, however, other forms of communication may be necessary, such as sign language or communication boards. Though children with PWS have problems with articulation, verbal ability often becomes a strength for them.

Developmental Delay/Learning Disabilities
IQS of individuals with PWS range from 40 to 105, with an average of 70. Those who do have an IQ in the “normal” range typically have learning disabilities and the spread of their abilities is mixed. Areas in which the child may have difficulties are with attention, short-term auditory memory, and abstract thinking. However, they do exhibit strengths in the areas of long-term memory, reading ability, and receptive language.

Diagnosis
There are several diagnostic studies used to test for PWS. Methylation analysis is a test that can detect virtually all cases of PWS, however, the test is not available everywhere. Therefore, FISH (for deletion cases) and PCR (for UPD cases) testing may be used. Together, these two tests will identify 99% of the cases. With the latest molecular testing available, patients who tested negative with older tests should be retested. In addition to genetic testing, diagnostic criteria for clinical recognition of PWS (as shown above) has also been made available.
Prognosis
Morbidity and mortality are secondary to complications:
· early hypotonia (e.g. aspiration);
later morbid obesity (e.g. coronary artery disease, hypertension, diabetes, sleep apnea)

www.pwsausa.org

www.members.attcanada.ca

www.thearc.org

www.netcom.ca

Retts
* Diagnostic Criteria
Required for the recognition of Rett syndrome after the exclusion of other handicapping conditions
· Period of apparently normal development until between 6-18 months
· Normal head circumference at birth followed by slowing of the rate of head growth with age (3 months -4 years)
· Severely impaired expressive language and loss of purposeful hand skills, which combine to make assessment of receptive language and intelligence difficult
· Repetitive hand movements including one or more of the following: hand washing, hand wringing, hand clapping, hand mouthing, which can become almost constant while awake
· Shakiness of the torso, which may also involve the limbs, particularly when upset or agitated
· If able to walk, unsteady, wide-based, stiff-legged gait/toe-walking

www.rettsyndrome.com
www.rsrf.org

Tourette Syndrome
Tourette syndrome is a condition that presents in childhood and is characterized by multiple motor and vocal tics that usually follow a waxing and waning course. It is commonly associated with a number of behavioral abnormalities and psychological disorders such as attention deficit hyperactivity disorder, obsessive-compulsive disorder and learning problems.

Diagnostic criteria
The DSM-IV diagnostic criteria for Tourette syndrome list the following as the basis for making the diagnosis:
· both multiple motor tics and one or more vocal tics must be present at some time, although not necessarily concurrently;
· the tics must occur many times a day (usually in bouts) nearly every day or intermittently over more than 1 year, during which time there must not have been a tic-free period of more than 3 consecutive months;
· the age at onset must be less than 18 years;
· the disturbance must not be due to the direct physiological effects of a substance (e.g. stimulants) or a general medical condition (e.g. Huntington’s disease or postviral encephalitis).
The ICD-10 calls the disorder `combined vocal and multiple motor tic disorder (de la Tourette’s syndrome)’ and classifies it as one of the tic disorders. The ICD-10 diagnostic criteria are less strict about the age of onset than the DSM-IV criteria.

Symptoms and Signs

Tics
A tic is a sudden, rapid, recurrent, nonrhythmic, stereotyped motor movement or vocalization. A hallmark of a tic is that the patient can suppress it for a period of time. Tics are often worse in times of anxiety, fatigue or other stress. They disappear during sleep in most patients.

Motor Tics
Motor tics may take many forms. They typically involve the face and head (e.g. blinking, mouth opening, grimacing, head shaking), although they may involve another part of the body.

Vocal Tics
A vocal tic may involve virtually any repetitive, stereotyped sound or utterance. Typical examples include sniffing, throat clearing, humming and coughing, but more obvious noises (such as barking or hooting) occur. Coprolalia affects a minority of patients.

Echopraxia, pallilalia and echolalia
Echopraxia, pallilalia and echolalia are often present in patients with Tourette syndrome.

Prognosis
In some patients, Tourette syndrome is a chronic condition that has onset in childhood and persists into adult age. In most patients, however, the condition remits in late adolescence and early adulthood, and remains subclinical.

Williams Syndrome

Diagnosis
Diagnosis is not easy as effects vary considerably, but the different clues can be added up to produce a near-certainty.

The cause of Williams Syndrome is a micro deletion of part of chromosome 7 which includes the Elastin Gene. A blood test (called the FISH technique) can establish if the Elastin Gene is in fact missing.

What are the clues?

Physical:
1. Facial Features. All the children have a facial similarity, referred to as ‘elfin’ features. They include a wide mouth, with large, slack bottom lip; very retrousse nose with flattened bridge; slightly ‘bulgy’ cheeks; irregular teeth widely spaced; sometimes a squint.

2. Early Problems. These can include low birth weight, often after being ‘late for dates’, slow weight gain – sometimes weight loss; below average growth; very slow feeding, restless sleeping, and irritability; sometimes a hernia, a squint and excessive vomiting leading to dehydration and constipation. A raised calcium level is found in some babies.

3. Heart Problems. All Williams Syndrome individuals appear to have a slight narrowing of the aorta above the valve, in many cases insignificant, but occasionally leading to more serious heart defects.

Psychological:
1. Hyperactivity in early years; extreme uninhibited behaviour, excessive talking, in an inappropriate and ‘adult’ manner, over-friendliness with strangers; compulsion to talk to adults, while being unable to make friends with peers. High verbal ability leading to artificial expectations of matching mental ability. Obsessional interest in certain things: e.g. cars, trains, hoovers, wheels, etc. Fear of heights, open stairs, uneven surfaces. Very short concentration span adding to learning difficulties, high distractibility. Emotional immaturity exhibited by over-reaction to events, and exaggerated displays of fear, excitement, sadness, happiness etc.

2. Hypersensitivity to Noise. This is the clue most common to all Williams Syndrome children: about 90% show great distress on hearing sudden loud noises, such as guns firing, balloons bursting, Christmas crackers, fireworks, etc.

www.willams-syndrome.org