Genetic Disorders

Chromosomal Abnormalities

1 Numerical abnormalities:
A.Autosomalchromosomes(triosomies&monosomies).
B. Sex chromosomes(triosomies & monosomies).

2. Structural abnormalities
deletion, translocation & inversion
 Numerical Aberration
• Autosomal
- Trisomies: 1 ch extra (e.g. trisomy 21-13-18)
- Monosomies: 1 ch is missing
• Sex chromosome
- Klinefilter syndrome (47, XXY male)
- Turner syndrome (45, XO female)
 Structural abnormalities
1) Translocation : the transfer of a chromosome or a
segment of it to a non-homologous chromosome.
2) Deletion : loss of a portion of a chromosome.
3) Ring chromosome
4) Duplication : extra piece of a chromosome.
5) Inversion : fragmentation of a chromosome followed
by reconstitution with a section inverted.
6) Isochromosomes : division of chromosome at
centromere transversely instead of longitudinally
 Numerical abnormalities
Trisomy i.e. 47 chromosomes
- Trisomy 21 (the extrachromosome is No 21)
- Klinefelter syndrome ( 47, XXY male)

Monosomy i.e. 45 chromosomes

- Monosomy 21
- Turner syndrome (the missing chromosome is X
in female : 45, X or 45 XO )
 1 Down Syndrome
Incidence :
• The most common chromosomal aberration
• Incidence 1/700 live birth & 10 % of M.R.

Definition : It is trisomy 21 i.e. the cell contain an

extra chromosome, number 21 i.e. the cell
contains three 21 chromosomes instead of two .
Figure 8.4 Translocation Down's syndrome. There is a translocation
between chromosomes 21 and 14 inherited from a parent
1 Chromosome abnormalities were found in 59 newborn infants with congenital
anomalies (39.3%) accounting for 2.3% of total NICU admissions.
The prevalence rate of chromosomal abnormalities was 0.42% (4.22/1,000 live
births(Intractable Rare Dis Res. )2021 May; 10(2): 81–87.
2.Aneuploidy is a general condition used for an abnormal number of chromosomes
consisting of one or more extra or missing chromosomesackson M, Marks L, May
GHW, Wilson JB. The genetic basis of disease. Essays Biochem. 2018 Dec
03;62(5):643-723. [PMC free article] [PubMed] [Reference list
3.Research has identified an extra chromosome copy for every chromosome, but
most of them are lethal during embryogenesis; even the known viable clinical
syndromes for trisomies are more frequently observed in spontaneous abortions
than in live birthsMcFadden DE, Friedman JM. Chromosome abnormalities in human
beings. Jackson M, Marks L, May GHW, Wilson JB. The genetic basis of
disease. Essays Biochem. 2018 Dec 03;62(5):643-723. [PMC free article] [PubMed] [
Reference list
Types of Down Syndrome?
There are three types of Down syndrome: Trisomy 21 (nondisjunction),
Mosaicism, and Translocation. Below is a chart that outlines the cell division
process of regular cells.
Trisomy 21 (Nondisjunction)

Down syndrome is usually caused by an error in cell division called

“nondisjunction.” Nondisjunction results in an embryo with three copies
of chromosome 21 instead of the usual two. Prior to or at conception, a
pair of 21st chromosomes in either the sperm or the egg fails to separate.
Trisomy 21 (Nondisjunction)
Down syndrome is usually caused
by an error in cell division called
“nondisjunction.” Nondisjunction
results in an embryo with three
copies of chromosome 21 instead
of the usual two. Prior to or at
conception, a pair of 21st
chromosomes in either the sperm
or the egg fails to separate
Mosaicism
Mosaicism (or mosaic Down
syndrome) exists when there
are a mixture of two types of
cells, some containing the
usual 46 chromosomes and
some containing 47. Those
cells with 47 chromosomes
contain an extra chromosome
21.
 Features of Down Syndrome
• Short height
• Severe mental deficiency
with decline in the IQ with
age
• Brachycephaly with flat face
and occiput
• Flat and low nasal bridge
• Upward slant to palpebral
fissures
• Malformed large ears
• Epicanthal folds of the
eyes
• Brushfield spots in iris
• Renal anomalies
• Prominent and protruding
tongue (scrotal tongue)
• Simian crease
• Clinodactyly of 5th digit
Associated congenital anomalies include
 congenital heart disease(40-50%)
 GIT anomalies(as duodenal atresia)
 cryptorchidisim
 cataract
 strabismus
 congenital hypothyroidisim(2%)
 hearing loss
 leukemia(20 times commoner).
• Triple test ( low estriol, low maternal serum alpha-
fetoprotein and elevated HCG) is often associated
with chromosomal syndromes; 15-18 weeks
• Quad screen (quad test): Triple test + inhibin A (↑ )
• Ultrasonography: nuchal thickening; 11-14 weeks
• Amniocentesis: chromosomal analysis; 15-18 weeks
• Chorionic villous sampling: chromosomal analysis;
10-12 weeks
1) Karyotyping = chromosomal study
• To establish diagnosis
• To determine genetic type for genetic counseling &
prognosis
2) Chest X - ray & echocardiography
for suspected congenital heart disease.
3) Others : hearing and vision testing and checking
thyroid profile due to increased risk of
hypothyroidism
 Management
• Supportive care :
1- Proper nutrition & medical care to diagnose and
manage possible complications.

2- Special social & educational care in specialized

institutes like speech therapy aiming to make the
child as independent as possible
 Turner syndrome
At Birth .. Edema of dorsum of hand &
feet
.. Webbing of neck.
Childhood period
- Short stature
- Head .. Low posterior hairline
- Neck .. Webbing of the neck
- Chest .. Broad chest & wide spaced
nipples
- Limbs .. Cubitus valgus
• Growth hormone therapy
• Estrogen replacement for
development of secondary sexual
characteristics at the time of
puberty (but infertility persists
1. he clinical assessment and management of children, young
people and adults with Down Syndrome: recommended clinical
practice: New Zealand Ministry of Health, 2001.
2 .Rosen T, D'Alton ME. Down Syndrome screening in the first
and second trimesters: what do the data show? Semin
Perinatol 2005;29:367-75.
3 .Christensen RD. Hematological problems in the neonate. 1st
ed. Phil: W.B. Saunders Co, 2000.