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(ILA1)

Clinical diseases

with chromosomal abnormalities

By

Dr Iman Marzouk

Professor of Pediatrics

Head of clinical genetics unit

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Diseases with chromosomal

abnormalitiesi

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Case (1):

A nine month old infant of a mother aged 38 years from

Alexandria. He was admitted to the hospital since 2 days,

C/O : Fever, cough, vomiting and tachypnea since 4 days.

Present history:

The infant was suffering from repeated attacks of pulmonary

infection, which might be preceded by an upper respiratory

tract infection.

He was admitted to the hospital for three times due to

pulmonary infections and inability to feed properly.

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Examination of the infant revealed:

Delayed mile stones,

Facial features of Down syndrome,

Hypotonia,

Congenital heart disease.

The following investigations were done:

X ray chest: Patches of consolidations

(Bronchopneumonia).

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Down Syndrome

(Trisomy 21)

It is the most common pattern of

malformation in man due to trisomy for all

or a large part of chromosome 21.

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Click to edit Master text stylesSecond level Third level Fourth level

Fifth level

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Clinical presentation

During neonatal period (1st month of life)

Abnormal facial features.

Simian crease.

Hypotonia, hyper flexibility of the joints.

Congenital malformation (Congenital heart

disease, duodenal atresia).

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During infancy (1 month to 2 years):

Characteristic facial features

Delayed mile stones (motor, language and

mental deficiency).

Repeated upper and lower respiratory tract

infections.

During childhood:

Characteristic facial features

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Clinical abnormalities

General Hypotonia:

delayed motor mile stones

Opened mouth with frequent protrusion of

the tongue.

Acrobatic movements.

Central nervous system (CNS):

Mental deficiency.

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Craniofacial:

Brachycephaly with relatively flat occiput.

Upslanting of palpebral fissures.

High arched hard palate and small nose with

low nasal bridge.

Inner epicanthic folds.

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Prominent forehead, flat face, short nose with flat nasalbridge,

Up slanting palpebral fissures , epicanthic folds andprotruded tongue.

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Eyes:

Brush field spots in the iris.

Lens opacities ------- cataract.

Refractive errors mainly myopia.

Nystagmus

Strabismus.

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Adult patient with Down syndrome. Note bilateralcataract.

Click to edit Master text stylesSecond level

Third level Fourth level Fifth level

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Ears:

Small over folding of angulated upper helix

Hearing defects (conductive and/or

sensorineural ).

Hair:

Fine, soft and sparse.

Dentition:

Hypoplasia

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Simian crease.

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Feet:

Wide gap between 1st and 2nd toes with

planter crease in between.

Cardiac:

Many cardiac defects like ventricular septal

defect (VSD), atrial septal defect (ASD).

Genitalia:

Primary gonadal deficiency.

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wide furrow between the big toeand other toes

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Natural History

Muscle tone tends to improve with age.

The rate of developmental progress slows

with age.

Early developmental intervention programs

for DS children have resulted in improved

rate of progress during the first five years

of life.

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The median age of death is about 50 years.

The major causes of early mortality:

Congenital heart defects

Low immunity leads to frequent respiratory

infections and high incidence of hepatitis B.

Leukemia.

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Etiology of Down Syndrome(DS)

It is a trisomy for all or a large part of chromosome

number 21.

Type Percent (%)

Non disjunction 94%

Mosaicism 2.5%

Translocation 3.5%

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Incidence of DS:

About 70% of trisomy 21 fetuses abort spontaneously.

The incidence is generally: 1:700 newborn.

According to the maternal age:

Maternal age Incidence

15-29 years 1:1500

30-34 years 1:800

35-39 years 1:270

40-44 1:100

45 years 1:50

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Recurrence rate:

It is about 1% in case of non disjunction DS.

In case of translocation DS :

The translocation is de novo in 70% of cases;with recurrence rate 1%.

If one of the parents is a carrier for

translocation (30% of cases), the recurrence

rate is about 10-15%; except if the carrier has

t(21,21) or isochromosome 21, where the

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Case (2):A fourteen year old girl

C/O: Short stature and delayed menarche

There was past history of edema of the dorsum

of the hands and feet.

Examination revealed:

Proportional short stature

Neck webbing

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Turner Syndrome (TS)

(X0 Syndrome)

It is a chromosomal syndrome of short

female with sexual infantilism and certain

physical abnormalities.

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Incidence of TS:

About 99% of 45X fetuses abort

spontaneously and only 1% of these

fetuses survive to term.

Despite this TS incidence is 1: 2500 live

births.

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Clinical presentations:

During neonatal period:

Edema of the dorsum of the hands and

feet.

Webbed neck.

Wide spaced nipples.

During the childhood:

Short stature.

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Short webbed neck in the previous neonatewide spaced nipples

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Edema of the dorsum of the hands and feet in a neonatewith turner syndrome

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Clinical Abnormalities

Growth:

Short stature.

Performance:

Low school performance (mild).

Although early development is usuallynormal, delayed motor skills are common.

Gonadal hypoplasia (estrogen therapy).

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Mild facial dysmorphism:

Narrow maxilla

Micrognathia

Downturned mouth angles

Prominent ears.

Neck:

Low posterior hair line.

Short webbed neck.

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A girl with turnersyndrome Note:

webbing of the neck ,wide-spaced nipples

and an increased

carrying angle at theelbows.

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Short webbed neck from thefront

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Short webbed neck from

the back

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Etiology of TS:

Fault chromosomal distribution leading to

45,X0 (monosomy X) individual.

Paternal X or Y chromosome is one more

likely to be missing.

Other chromosomal anomalies:

46XX/45X0, isochromosome X, partial

deletion of one of the X chromosomes.

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Case (3):A five month old infant

C/O: Low birth weight, delayed mile stones,

failure to thrive and a cat like cry specially in

the early months of life.

Her examination revealed rounded face,

inappropriate growth and delayed development.

Karyotype: 46, XX, 5p-

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Cri du Chat syndrome

Microdeletion (5p-

syndrome)There is partial deletion of the short arm of

chromosome number 5.

85% of the cases occurs de novo and from

unbalanced translocation from one of theparents in 15% of the cases.

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Click to edit Master text stylesSecond level Third level

Fourth level Fifth level

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Flat occiput, microcephaly andlow set ears in an infant with cri

du chat.

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Girl with cri du chat: notethe rounded face and

hypertelorism.

Hand of the same girlshowing simian

crease.

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The risk of recurrence:

1% if the parents are normal.

15-25% in case of parental translocation.

Incidence:

1:20000 live births.

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Clinical presentation

Abnormal cat like cry in early neonatal

period (disappear later)

Low birth weight.

Slow growth (failure to thrive)

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ClinicalAbnormalities:Mental deficiency.

Hypotonia

Microcephaly

Round face (become elongated later)

Hypertelorism

Epicanthic folds

Downward slanting of palpebral fissure

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You

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hankYou