Genetic Syndromes

Chromosomes

Sex Linked SyndromesSex Linked Syndromes

Gene DefectsGene Defects

Development of Young Children with Disabilities#872.514 (61)

Carol Ann Heath

CHROMOSOMAL ABNORMALITIES

What is a Trisomy?

A chromosomal anomaly characterized by the presence of an extra chromosome in the cells

A trisomy occurs when there are 47 chromosomes instead of 46

A partial trisomy occurs when just part of an extra chromosome attaches to another

Trisomy continued

Mosaic trisomy occurs when the extra chromosome material is not present in every cell

The most common known trisomies are:

Trisomy 21 (Down syndrome)Trisomy 18 (Edward’s syndrome)Trisomy 13 (Patau’s syndrome)

Trisomy 21: Down syndrome

Extra 21st chromosome; 47 chromosomes in each cell

1/800 birthsApproximately 5,000 children with Downsyndrome born each year in U.S.1% chance of reoccurrenceLife expectancy: approximately 55

years

Down syndrome

96% of children with Down syndrome have the extra chromosome 21

4% have either a translocation (attached to or incorporated into another chromosome in the egg or sperm) or a form called “Mosaic” in which not all cells affected.

Mosaic children may be less delayed

Prevalence

Prevalence increases with maternal age:

29 years and younger 1/150030-34 years 1/80035-39 years 1/27040-44 years 1/100over 45 years 1/50

Physical Characteristics

Hypotonia short neckoval-shaped eyes (excess skin)epicanthal foldssingle palmar creasessmall noseflattened nasal bridgesmall oral cavitysmall ears that may fold slightly at top

Health problems associated with Down syndrome

40-50% have congenital heart defectsRespiratory problems, especially upper

respiratory infectionsEye and ear problems including hearing

lossThyroid problemsCervical spine abnormalitiesGastrointestinal problems

Down syndrome continued

Most have some degree of mental retardation ranging from mild to severe.

Average person functions in mild to moderate range.

Education in public schoolsPerform daily living skills independentlyCan marry and have children (rare for

men)Women have 50% their child will have DS

Development

Better prognosis due to:better health careearly interventionmore normal family and social

experiencesbetter educational opportunitiesmore positive social attitudes

Development continued

Social and emotional development in infancy delayed, they progress in the first year is essentially normal.

Hypotonia delays motor skills which restricts their early experiences.

Visual exploration and eye-contact delayed in first year.

Development continued

Expressive language skills delayedMay be able to sign words before

verbalizing them3/4 children have speech production

problems4/5 may experience some degree of

hearing loss (fluctuating caused by o.m.)

Development continued

Many children have auditory-perceptual impairment (tree/cheese)

At risk for dyspraxia-inability to perform coordinated movements

Benefits of sign language

A way of teaching speech and language

Method of communicating and expression

Develop comprehension of speech

Assisting with Language

Sign languagecomputersopen/closed questionsrole playsynthesized speech

Reading

Most early reading books contain too little text and text that is too complex

Reading single words first:matchingselectingnaming

Trisomy 13

Sometimes referred to as Patau SyndromeDescribed in 1657, etiology not

discovered until 1960 by Dr. Klaus PatauExtra 13th chromosome which results in

significant multiple defects in major organ systems

Brain most severely affectedMany born blind, deaf, no sense of smell

Trisomy 13

1/8000 birthsMedian survival is 2.5 days82% die within the first month5% survive first 6 monthsThose surviving longer have severe

mental defects, seizures, and failure to thrive

Only 1 adult known to survive to age 33

Abnormalities

80% heart defect60-80% cleft lip, cleft palate or bothFound in 50% or more patients:central nervous system hearingcranium eyesskin hands and feetskeletal genitalia

Etiology

Maternal age has been a factor with occurrence

Chance of recurrence is thought to be low

Trisomy 13 mosaicism usually show a less severe clinical phenotype, survival may be longer, and mental deficiency variable

Trisomy 18

Also known as Edward’s syndromeDiscovered in 1960 by Dr. John

EdwardsCaused by an extra 18th chromosomeIt is the second most common multiple

malformation syndrome1/6,600 birthsAffects females 3:1

Trisomy 18

50% die within first weekOnly 5-10% survive the first year as

“severely mentally defective individuals”10 children over the age of 10 reportedMost unable to walk and language limited,

but some older children who survive may interact and relate to family members.

Abnormalities

Growth deficiency congenital anomalies of the heart,

lung, kidneys, and diaphragmincreased muscle tonesmall mouth and jawmental deficiencymicrocephaly

Abnormalities continued

Low set malformed earssmall pelvis, limited hip abductionunderdeveloped nailsunderdeveloped or absent thumbsabnormal genitaliaepiscanthal folds

Etiology

Maternal age contributing factor to occurrence

1% chance of recurrenceMoscaicism leads to partial clinical

expression, longer survival and various degrees of variations

Sex Linked

Abnormality in the overall number of chromosomes for X and Y

Male has one X and One YFemale has two X

Disorders

Turner syndrome: female abnormalityFemale has only one X, total of 45,

not 46 chromosomes, resulting in XO pattern

Only case in which too few chromosomes can develop into an embryo and survive

1/5000 female births

Turners

Very short <5 ftLowered hairline, broad chest and

short neckOvaries do not function normallyIQ in typical range with learning

disabilities, particularly visual-perceptual and mathematics

Klinefelter syndrome

Males has extra X chromosome, resulting in 47

Pattern of XXY1/500 malesTaller and thinner; underdeveloped

secondary sex traits; decreased hormone level

Language delays; normal adulthood

Chromosome deletions

Sometimes genetic material is missing from a chromosome. These chromosomes are said to have “deletions”.

Interstitial deletions occur when a chromosome has broken, genetic material has been lost, and the chromosome arms rejoin

Larger deletions lead to death

Chromosomal Errors

Deletion #22q11.2 syndromeWilliams syndromeFragile XCri du chat

Cri du chat syndrome

First described in 1963 by LejeuneSyndrome associated with deletion of

the short arm of chromosome5Deletion can vary in size from

extremely small (involving only one band) to the entire short arm

Majority of children die in early childhood, some survive into adulthood with low IQ

Prevalence

One of the most common deletion syndromes

Varying between 1/20,000 and 1/50,000

Abnormalities

Low birth weight 72%Slow growth 100%cat-like cry 100%hypotonia 78%mental deficiency 100%microcephaly 100%strabismus 61%

Abnormalities continued

Round face 68%epicanthal folds 85%Low set and/or poorly

formed ears 57%congenital heart disease 30%

Development

As babies, unusually squirmyCat-like cry that becomes less prominent

with ageWith special schooling and supportive

home environment, some children have attained social and psychomotor skills of a 5 to 6 year old

50% had vocabulary adequate for communication

William syndrome

Described in 1961 by Williamsdeletion of one allele located within

chromosome subunit 7q11.231/20,000 births

Abnormalities

Mild growth deficiencymild microcephalysmall upturned noselong philtrumepicanthal foldscardiac anomaliesjoint limitations

Performance

Average IQ is 56 (range 40-80)Hoarse voiceHypersensitive to soundMild neurologic dysfunctionPoor coordinationDecreased perceptual and motor functionLanguage ability much greater than

cognitive ability

Development

Infancy: feeding problems, colicky, fretful

Childhood: outgoing, no fear of strangers, strong interest in others

2/3 of children: difficult temperament, more negative moods, increased activity, distractible, less persistence, and low threshold arousal

Development continued

As adults: progressive medical problems

Most live with parents or in group home

Sudden death reported in a number of children

Deletion #22q11.2 syndrome

Previously known as DiGeorge syndrome1 out 5000 birthsCommon cause of genetic heart

malformationFacial anomalities: small mouth, narrow

eyes, bulbous nose, palate Immune deficiencyTypical cognitive ranges with learning

disabilities, particularly in math

Fragile X Syndrome

Mental Impairment

Females: learning disabled in math exceptional with reading and spelling 1/3 have mental disabilities similar to those

associated with schizophreniaMales:

process information in simultaneous fashion Sees whole in order to understand the parts

Speech and Language

Rapid burstsEcholalicPerseveration most difficulty for malesTalking inappropriatelyOne topicSpeech problems made worse if

anxious

Behavioral Problems

ADHDTemper tantrumsMood swingsAggressionStrong reaction to change in

environmentSensory integrationAutistic like behaviors

Medical Problems

At greater risk for otitis mediaMyopia“Lazy eye”Orthopedic difficulties related to flat

feet and joint laxity20% of males prone to seizuresDigestive disorders

Education

Early InterventionMainstreamingOccupational therapySpeech therapyPhysical therapyVisual devices

Fragile XFragile X

Identified by a break or weakness on the long arm of the X chromosome

FMR-1X linked“Genetic anticipation”Testing for Fragile X

Fragile X syndromeFragile X syndrome

Most Common Genetically inherited form of mental retardation

1991 clinical method of diagnosing

Occurs in 1/1000 male birthsOccurs in 1/2500 female birthsLife span is normal

Physical Characteristics

Long narrow faceLarge or prominent earsMacroorchidismAbnormalities of connective tissue:

double jointed fingersFlat feetHeart Murmur

Mental Impairment

80% of males have mental impairment ranging from severe retardation to low-normal intelligence

Majority: mildly to moderately retarded30% of females have some degree of

mental retardationIQ appears to decline with age

Mental Impairment cont.

Common learning disabilities include delayed speech attention problems hyperactivity math

Good with imitationVery socialVisual Memory