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CHROMOSOMAL DISORDERS

CHROMOSOMES

• DNA – containing threadlike structures in the

nucleus that carry genetic information
• Chromosomes exists in pairs
• Normal human cells carry 23 pairs or 46
chromosomes
• This includes one pair of sex chromosomes XX
(female) or XY (male)

ANEUPLOIDIES

DOWN SYNDROME
RISK CORRELATE WITH MATERNAL AGE
• Etiology: presence of chromosome 21
• <25 y/o 1/1600
• Risk factors: advanced maternal age, altered
chromosome recombination • 30 to 34 y/o 1/800
• Diagnostic methods: amniocentesis and • 35 to 39 y/o 1/270
chorionic villus sampling, routine karyotyping, • > 40 y/o 1/80
paralogous sequences
• Clinical presentation:
- Muscular hypotonia, short neck with loose
skin on the nape, flat nasal bridge and facial
profile, small head, ears and mouth,
protruding tongue, upward slanting eyes,
Brushfields’ spots, Simian crease, short
broad hands and short little finger, deep
grove between 1st and 2nd toe
• Associated conditions: congenital heart disease,
gastrointestinal disorders, thyroid problems,
orthopedic (hip dysplasia, cervical spine
instability, ligamentous laxity, weakness,
scoliosis, arthropathy), vision and hearing
• Rehabilitation: motor learning strategies,
CHARACTERISTIC APPEARANCE
motivation strategies, consideration to
movement pattern • Hypotonia with tendency to keep mouth open
DOWN SYNDROME (TRISOMY 21) IS THE MOST and protrude the tongue;
COMMON AUTOSOMAL TRISOMY COMPATIBLE WITH • Excessive mobility, flexibility of joints.
LIFE • Relatively small, short stature with awkward gait

• Trisomy 21 (95 %) CENTRAL NERVOUS SYSTEM

• Some cases result from translocation • Mental retardation (mean IQ< 50)
• More rarely, mosacism (about 2%) • Developmental delay
• Karyotype=47,XX+21 or 47,XY+21 • Hypotonia
• Alzheimer-like dementia
• Signs of hypothyroidism

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• Leukemia

• Microcephaly (small brain),

• brachycephaly (short skull) with relatively flat
occiput
• Flat facial profile
• Short, up slanting palpebral fissures
• Small nose with flat nasal bridge;
• Brushfield, speckled spots of the iris
• Inner epicanthal folds

• Small mandible, small mouth with protruding • Rough skin

tongue • Mentally retarded
• Small ears with abnormal shape • Small round face
• Late closure of fontanels; • Protruding tongue
• Impotency in males
• Short lifespan

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“HAPPY CHILDREN” • With early intervention and special education,

many learn to read and write and participate in
various childhood activities.

EDWARD SYNDROME

PALM OF THE PATENT WITH DOWN SYNDROME
• Chromosome disorder caused by the presence
of an extra chromosome 18
• Manifestations:
- Growth deficiency, cardiac problems, kidney
disorders, thyroid and adrenal hypoplasia,
Meckel’s diverticulum and hernias
- Mean life expectancy: 4 days

Trisomy 18

• Incidence 1/8000
• Sever Mental retardation and many physical
birth defects
• >90% dead in 1styear
• severe birth defects + mental retardation
Cardiac – CHD: Atrioventricular Septal Defect (AV-Canal)

Before birth

• Polyhydramnios,
• Small placenta
• Intrauterine growth retardation

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After birth

• Craniofacial dysmorphism (strawberry-shaped

head)
• Microcephaly
• Micrognathia (small mandible)

• Overlap of second finger on third, fourth finger

on fifth
• Fixed finger contractures

• Weak cry
• Small sternum, small nipples and pelvis
• Hypoplasia of skeletal muscle, subcutaneous
and adipose tissue.
• CHD, horseshoe kidney, and omphalocele
(infant's intestine or other abdominal organs are
outside of the body because of a hole in the
belly button (navel) area)

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PATAU SYNDROME VARIABLE DEFECT IN FACIAL DEVELOPMENT

• Abnormality in trisomy 13
• 1/12,000 births
• Has the greatest negative impact on survival
• Risk factor: advanced maternal age
• Manifestations:
- Sloping forehead, small malformed ears,
anopthalmia/microthalmia, micrognathia,
pre-auricular tags
- Has facial and extremities defects, CNS
abnormalities, cardiac disorders, other
organ disorders (liver, kidneys and GI tract,
etc.)

Trisomy 13

• severe birth defects

• mental retardation

• CNS malformations, midline brain defect,

holoprosencephaly Holoprosencephaly (HPE)isa
cephalic disorder in which the prosencephalon
(the forebrain of the embryo) fails to develop
into two hemispheres.
• CHD - variety of cardiac defect

• IUGR – intrauterine growth retardation

• Open scalp lesion, scalp defect (cutis aplasia)
• Cleft palate (may be bilateral)
• Microcephaly
• Malformed ears
• Microphthalmos

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PROGNOSIS

• 50% of patients die before 1 month of age

• 70 % - die before age 6 month,
• 90 % - die before age 1 year

Newborn boy with diagnosed Patau syndrome (cleft lip

and palate, polydactyly of left hand, atrial septal defect)

Boy 5 yrs old with Patausyndrome (congenital deafness SEX CHROMOSOMES VARIATIONS
and blindness)
TURNER SYNDROME

• Genetic condition caused by a missing X-

chromosome
• Associated complications: bicuspid aortic valve
• Aortic dissection, coarctation of aorta
• Physical therapy rehabilitation: growth hormone
and estrogen replacement therapy, addition of
androgen to GH
• Affects 1 in 2500 newborn girls;
• One X chromosome is either missing or
abnormal; •In 55% of girls who have Turner
syndrome there is a 45, X karyotype; •In 25 % of
patients – the structure of one of the X
chromosomes is altered (deletion, duplication).
• in 15 % of patients – mosacism

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PRENATAL DIAGNOSTICS OF TURNER SYNDROME

Blister chrome of neck area and edema of fetus

XO SYNDROME (TURNER SYNDROME)

Short Female, Broad Chest with Wide Space of Nipples,

Congenital Lymphedema

• Dysmorphic features– lymphedema of hands

and feet at birth,
• shield-shaped chest,
• webbing of the neck,
• appearance of short neck
• low posterior hairline,
• Cubitus valgus (increased carrying angle) • RENALanomalies (40 %) include duplication of
• Short stature (height adult – 135 cm the collecting system and horseshoe kidney.

• CHD (20 %) – bicuspid aortic valve. Dissecting

aortic aneurysm in young adulthood may be a
serious complication.

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• Thorax.Broad chest with widely spaced nipples • Treatment: hormone therapy, speech and
that may be hypoplastic; often mild pectus physical therapy, education
excavatum
HYPOGENITALISM AND HYPOGONADISM. LONG LEGS,
DULL MENTALITY, AND/OR BEHAVIORALS

• 80 % - children with Klinefelter syndrome have a

male karyotype with an extra chromosome X-
47,XXY
• 20% - have multiple sex chromosome
aneuploidies (48,XXXY; 48,XXYY; 49,XXXXY),
mosaicism(46,XY/47,XXY);
• 20% of aspermic adult male (blocked
spermatogenesis

PROGNOSIS

• Depends on the type and severity of

malformations
• Life span probably normal in most cases

KLINEFELTER SYNDROME

• Common male disorder

• Clinical features: tall stature, gynecomastia, • Puberty occurs at the normal age, but the testes
hypogonadism, infertility, learning disabilities, remain small.
problems with socialization • Patients develop secondary sex characters late;

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• 50% develop gynecomastia. • Treatment: Symptomology

• They have taller stature.
• Because many patients with Klinefelter
syndrome are phenotypically normal until
puberty, the syndrome often goes undiagnosed
until they reach adulthood, when their infertility
aids in their clinical identification.
• Patients with 46,XY/47,XXY have a better
prognosis for testicular function.

DELETION 5P SYNDROME (CRI-DU-CHAT, CAT’S CRY

SYNDROME)

The cause of this syndrome is a deletion of part of the

short arm of chromosome 5.

ABNORMALITIES

• Low birth weight (lessthan 2.5 kg)-72%

• Slow growth-100%
• Cat-like cry-100%
• Their intelligence shows variability and ranges • Mental deficiency-100%
from above to below average. • Hypotonia-78%
• Persons with KS can show behavioral problems,
learning disabilities, and deficits in language.
Problems with self-esteem are often the case
with adolescents and adults.
• Those who have higher X chromosome counts
show impaired cognition. It has been estimated
that each additional X chromosome reduces the
IQ by 10-15 points, when comparing these
persons with their normal siblings.
• The main effect is seen in language skills and
social domains.

CRI DU CHAT (“CAT’S CRY)

• Chromosome 5 depletion syndrome

• Characteristic cry of affected infants are similar
to a meowing kitten due to problems with
larynx
• Hallmarked by underdeveloped larynx

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CAT-LIKE CRYIN INFANCY, MICROCEPHALY, DOWNWARD

SLANT OF THE PALPEBRAL FISSURES

• Beginning in the newborn period and continuing

through the first few months of life
• Children affected with this disorder have a
striking cat-like cry that is caused by laryngeal
hypoplasia

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