COMMONWEALTH ASSOCATION FOR
EDUCATION, ADMINISTRATION AND
MANAGEMENT
VOLUME 1 ISSUE 4
ISSN NO 2322-0147
DECEMBER
2013
Mental Retardation:
A Review of The Genetic Causes
Excellence International Journal of Education and
Research (Multi- subject journal)
Excellence International Journal Of Education And Research
VOLUME 1
ISSUE 4
ISSN 2322-0147
Mental Retardation: A Review of The Genetic Causes
Address for Communication:
Ms.Priya Magesh,
No 5, Angels Cottage,
Main Cross Street,
Kamaraj Nagar, Avadi,
Chennai-600071.
Ms.Priya Magesh,
Assistant Professor,
Department of Counselling Psychology,
Madras School of Social work,
Egmore,Chennai-08.
Mobile-9962133306
E- mail- priyamagesh@ymail.com.
ABSTRACT
Mental retardation is a heterogeneous disorder consisting of below average intellectual
functioning and impairment in adaptive skills that is present before the person is 18 years of age.
The impairments are influenced by genetic, environmental and psychosocial factors. During the
past decade, increased recognition has been given to subtle biological factors, including small
chromosomal abnormalities, genetic syndromes, subclinical lead intoxication and various
prenatal toxic exposures in persons with mild mental retardation. In past years the development
of mild mental retardation had traditionally been attributed mainly to psychosocial deprivation.
The genetic causes for this disorder are briefly explained.
Key words-Genetics, Mental retardation
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Mental retardation is a disorder which refers to significantly sub average general intellectual
functioning, resulting in or associated with concurrent impairment in adaptive behavior and
manifested during the development period. Adaptive behavior is defined as the degree with
which the individual meets the standards of personal and social responsibility expected of his age
and cultural groups. The expectations of adaptive behavior vary with chronological age. During
infancy and early childhood, the impairment is found in areas of sensory motor skills,
communication skills, self-help skills and socialization. During childhood and adolescence
period, the deficits are in the area of application of basic academic skills to daily life activities,
application of appropriate reasoning and judgment in the mastery of environment and in
application of Social skills. During late adolescence and adult life, the adaptive behavior deficits
are found in the area of vocational and social responsibility.
NOMENCLATURE
The term “Mental Deficiency” was used interchangeably with “Mental retardation “until
recently, when the association for Mental Retardation chose “Mental retardation as the preferred
term. WHO has recommended the term “Mental Sub-normality”, which includes two categories:
Mental retardation (subnormal functioning secondary to identifiable underlying pathological
causes) and mental deficiency (I.Q. of less than 70), which is often used as a legal term.”Mental
Handicap” and “Mentally Challenged” were also used until recently to denote a mild form of
mental retardation.
CLASSIFACTION
The degree or levels of mental retardation are expressed in various terms.DSM IV TR presents
five types of mental retardation, reflecting the degree of intellectual impairment. Mild Mental
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Retardation is the most Commonest type, accounting for 85-90%.The IQ level ranges between
50- 70.Diagnosis is made usually later, at preschool period (before 5 years).This group has been
referred as ‘Educable’. Moderate Mental Retardation type of mental retardation accounts about
5-10%, where the IQ level ranges between 35-50. This group has been referred as ‘Trainable’.
Severe Mental Retardation type of mental retardation accounts about 20-35, where the IQ level
ranges between 20- 35, Often diagnosed early with poor motor development and absence of
speech and other communication skills. These groups are referred as ‘Dependent’. Profound
Mental Retardation accounts for 1-2%, with IQ<20.They may have associated physical disorders.
This group needs ‘Life support’ under a carefully planned and structured environment.
Severity Unspecified type of mental retardation
should be used when there is a strong
presumption of mental retardation, but the person cannot be successfully tested by standard
intelligence test. This may be the case when children, adolescents are too impaired or
uncooperative to be tested.
ETIOLOGY
Causative factors in mental retardation include Genetic (5% of cases) conditions such as Down’s
Syndrome (Trisomy 21), Fragile X Syndrome, Turner’s Syndrome(44+XO) and Klienfelter’s
Syndrome( 44+ XXY or 44+ XXX). Inborn errors of metabolism
involving
amino acids
(Phenylketouria,Homocystinuria),Lipids( Tay Sachs disease,Nieman-pick disease),Carbohydrate
( Glycogen storage
diseases, Galactosemia), Purines( Lesch Nyhan Syndrome).Single gene
disorders such as Neurofibromatosis, Tuberous sclerosis and may be to Cranial Anomalies such
as Microcephaly where the head is much smaller
than normal. The skull is usually long and
narrow. Hydrocephalus – a condition where the head is distended as a result of too much of
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Cerebrospinal fluid in the brain and Spinabifida,a condition in which the development of the
spinal cord and its covering is incomplete.
Perinatal factors such as (probably in 10% of cases) Infections – Rubella, Syphilis, Prematurity,
Birth trauma, Hypoxia, Intra uterine growth retardation (IVGR), Placental abnormalities, Drugs
during first trimester and Fetal alcohol syndrome. Acquired physical disorders
(probably
in
2-5%
of
cases)
such
as
in
Infections,
childhood
especially
Encephalopathy,Cretinism,Trauma,Lead Poisoning and Cerebral palsy – paralysis of limbs due
to brain damage and sociocultural Causes (15%) in which deprivation of socio-cultural
stimulation.
SPECIAL FOCUS ON GENETIC CAUSES
Down’s Syndrome:
Down’s Syndrome was first described by the English Physician Langdon Down in 1866 and was
based on physical characteristics associated with subnormal mental functioning. Since then,
Down’s Syndrome has remained the most investigated and the most discussed syndrome in
mental functioning. Down syndrome is the most frequent genetic cause for mild to moderate
mental retardation. It is a chromosomal disorder caused by an error in cell division that results in
the presence of an additional 3 chromosomes or trisomy 21 because of their physical
characteristics of slanted eyes, epicanthal folds and flat nose. There is an agreement on a few
disposing factors among them, the increased age of the mother, and possibly increased age of the
father and X-ray radiation. The problem of the cause is complicated even further by the recent
recognition of three types of chromosomal aberrations as follows (1) patient with trisomy 21
represent the overwhelming majority, they have 47 chromosomes, with an extra chromosome 21.
(2)Non disjunction occurring after fertilization in any cell division results in mosaicism,a
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condition in which both normal and trisomic cells are found in various tissues. (3)In
translocation there is a fusion of two chromosomes, mostly 21 and 15, resulting in a total of 46
chromosomes, despite the presence of an extra chromosome 21.The diagnosis of Down’s
syndrome is made relative ease in older child but often difficult in new born infants. The most
important signs in a new born include general hypotonia, oblique palpebral fissures, abundant
neck skin, a small flattened skull, high cheek bones and a protruding tongue. They have an
increased frequency of respiratory infections and X-ray chest may show some abnormalities.
Life expectancy used to be 12 years and with the advent of antibiotics, few young patients
succumb to infections, but many of them do not live beyond the age of 40.Person with Down’s
syndrome tend to show a marked deterioration in language,memory,self-care skills and problem
solving in their 30s.
Fragile X syndrome:
Fragile X syndrome is the second commonest chromosomal aberration causing mental
retardation. Fragile X syndrome is the most common inherited form of mental retardation The
characteristic presence of a fragile site at the tip of the long arm of X chromosome appears as a
constriction. The syndrome results from a mutation on the X chromosome at what is known as
the Fragile site (Xq27.3).It results from a change or mutation in a single gene, which can be
passed from one generation to the next. Symptoms of fragile X syndrome occur because the
mutated gene cannot produce enough of a protein that is needed by the body’s cells, especially
cells in the brain to develop and function normally. The most noticeable and consistent effect of
fragile X syndrome is on intelligence. The underlying cause of fragile X is a change in a single
gene, the fragile X Mental Retardation 1 (FMR1) gene, which is located on the X chromosomes
to make FXMRP/FMRP.
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Table 1 showing inheritance of Fragile X Syndrome
Diagram B:
Diagram A:
Mother
Father
Y
X
X
X
YX
YX
Boy
Boy
XF X
XF X
Girl
Girl
Father
Mother
XF
X
XF Y
XF X
Boy
Girl
XY
XX
Boy
Girl
Y
XF
The gene for fragile X is carried on X chromosome. Both male (XY) and female (XX) have at
least one X chromosome; both can pass on the mutated gene to their children. The metabolic
disorder that affects intelligence and development are typically caused by the pairing of two
defective recessive genes, one from each parent. Fragile X syndrome is believed to occur in
about 1 in every 1,000 males and 1 in every 2,000 females. The typical phenotype include a
large long head and ears, Short stature, Bat’ ears, Long face and associated with psychiatric
disorders like Attention Deficit/Hyperactive Disorder. Persons with fragile X syndrome seem to
have relatively strong skills in communication and socialization and their intellectual functions
seem to decline in the pubertal period. Females carriers are often less impaired than are males
with fragile X syndrome, but females can manifest the typical physical characteristics and can be
mildly retarded.
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William’s Syndrome:
William’s syndrome is a genetic condition that is a cause of mental retardation. It is relative new
comer on the cause of retardation. The cause of the disorder is a mutation of chromosome 7, a
fragment of chromosome 7 is missing in the individual make up. The mutation is random rather
than inheritable. Tiny upturned nose, Small chin, distended skin around the eyes and Short
stature are the characteristic features of William’s Syndrome.
Prader-Willi Syndrome:
Prader-Willi Syndrome is postulated to be the result of a small deletion involving chromosome
15, usually occurring sporadically. Its prevalence is less than 1 in 10,000.Persons with the
syndrome
exhibit
compulsive
eating
behavior
and
often
obesity,
mental
retardation,hypogonadism,small stature,hypotonia and small hands and feet. Children with the
syndrome often have oppositional and defiant behavior.
Cat-cry (cri-du-chat) Syndrome:
Children with cat-cry syndrome are missing part of chromosome 5 .They are severely retarded
and show many stigmata often associated with chromosomal aberrations such as
microcephaly,low set ears, oblique palpebral fissues,hyper telorism and micrognathia.The
characteristic cat like cry caused by laryngeal abnormalities that gave the syndrome its name
gradually changes and disappears with increasing age.
Phenylketouria:
Phenylketouria was first described by Ivar Asbjorn Folling in 1934 as the paradigmatic inborn
error of metabolism. It is transmitted as a simple recessive autosomal mendelian trait and occurs
in about 1 in every 10,000 to 15,000 live births.PKU is an inborn error of metabolism. The basic
defect is the absence or the inactivity of phenylalanine hydroxylase of phenylalanine to Para
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tyrosine conversion, which results in marked increase in blood phenylalanine levels and its
metabolites. Babies with PKU appear normal at birth, but cannot break down the Amino acid
phenylalanine .The chemical builds up and is converted into substances that poison the system ,
causing severe retardation and several other symptoms. The majority of people with PKU are
severely retarded, but some are reported to have borderline or normal intelligence.Eczema,
vomiting and convulsions are present in about a third of all cases. Although the clinical picture
varies, typical PKU children are hyperactive and exhibit erratic, unpredictable behavior which
makes them difficult to manage. They frequently have temper tantrums and often display bizarre
movements of their bodies and upper extremities and twisting hand mannerisms. Verbal and nonverbal connnmunucation is usually severely impaired or nonexistent. The children’s coordination
is poor and they have many perceptual difficulties. The disease was previously diagnosed on the
basis of a urine test, currently a more reliable screening test, namely Guthrie inhibition assay,
which uses bacteriological procedure to detect blood phenylalanine. Early diagnosis is important,
as a low phenylalanine diet, in use since 1955, significantly improves both behavior and
developmental progress. The best results seem to be obtained with early diagnosis and the start
of dietary treatment before the child is six months of age. Children who receive a diagnosis
before the age of 3 months and are placed on an optimal dietary regimen may have normal
intelligence. The disease can be detected by a phenylalanine tolerance test ,which may be
important in the genetic counselling of the people.
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TABLE-2 METABOLIC PATHWAYS OF PHENYLALANINE
Phenylalanine
Absent
10- 25 times more
Phenylalanine
Phenylalanine
Hydroxylase
Phenylalanine Pyruvic acid
Para tyrosine
Tyrosine
Phenyl lactic acid
Phenyl acetic acid
Phenyl acetyl glutamate
Normal Pathway
Abnormal Pathway
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RETT’S DISORDER:
Rett’s Disorder is hypothesized to be an X-linked dominant mental retardation syndrome
that is degenerative and affects only females.Andreas Rett reported on 22 girls with
serious progressive neurological disability in the year 1966.Deterioration in
communication skills, motor behavior and social functioning starts at 12 to 18 months of
age. Autistic like symptoms are common as ataxia, facial grimacing, teeth grinding an
loss of speech, Intermittent hyperventilation and a disorganized breathing patterns are
characteristic while the child is awake. Stereotypical hand movements, including hand
writing are typical. Progressive gait disturbances, scoliosis and seizures occur. Severe
spasticity is usually present by middle childhood.
COURSE AND PROGNOSIS
In most cases of mental retardation, the underlying intellectual impairment does not improve, yet
the affected person’s level of adaptation can be positively influenced by an enriched and
supportive environment.
TREATMENT
Mental retardation is associated with several heterogeneous groups of disorders and a multitude
of psychosocial factors. The best treatment of mental retardation is prevention, which happens at
three levels.
Primary Prevention:
Primary prevention concerns actions taken to eliminate or reduce the conditions that lead to the
development of the disorders associated with mental retardation. Such measures include
(1)Improvement in socio-economic condition of society at large aiming at elimination of under
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stimulation, malnutrition, prematurity and perinatal factors.(2)Education of lay public, aiming at
removal of misconceptions about mentally retarded individuals.(3)Medical measures for good
perinatal medical care to prevent infections, trauma, excessive use of medications, malnutrition,
obstetric complications and diseases of pregnancy.(4)Family and Genetic counselling in at risk
parents e.g., Down’s syndrome.
Secondary Prevention
Once the disorder has been identified ,the disorder should be treated to shorten the course of the
illness.These measures include (1)Early detection and treatment of preventable disorders e.g.
Phenylketonuria, Hypothyroidism.(2)Early detection of handicaps in sensory motor or behavioral
areas with early remedial measures and treatment.(3)Early treatment of connectable disorders
e.g. infections (antibodies), skull configuration anomalies (surgical correction).(4)Early
recognition of presence of mental retardation. A delay in diagnosis may cause unfortunate delay
in rehabilitation.
Tertiary Prevention:
This is to minimize the disability of the individual with mental retardation .The measures are (1)
Treatment
of
psychological
and
behavioral
problems.(2)
Behavior
modification
(3)Rehabilitation in physical, social and vocational areas, which commensurate with the level of
handicap.(4)Parental Counselling and (5)Institutionalization for individuals with profound MR.
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REFERENCES
Bregman J D (1991): Current developments in the understanding of mental retardation,
Psychopathology,
Brown W T (1997): The Fragile X Syndrome, Journal of American Academic child Psychiatry
7,701-703.
Crocker A C (1989): The causes of mental retardation.Peadiartics Annals 20, 76-79.
Dykens E M (1992): Adaptive and maladaptive behavior in Prader-Willi Syndrome, Journal of
American Academy Child Adolescence Psychiatrity, 31, 1131- 1134.
Hagberg B A (1989): Rett Syndrome: Clinical peculiarities, diagnostic approach and possible
cause, Pediatric Neurology, 5, 75-79.
Hurley A D (2007) Individual Psychotherapy with Mentally retarded individuals: A review and
call of research. Research developmental disability, 10,261-264.
Szymanski L S,Crocker AC(1989): Mental retardation. In comprehensive Text book of
Psychiatry, 5th edition, Williams & Williams, Baltimore.
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