down syndrome . klinefelters syndrome . pathology seminar mbbs student

1. TRISOMY 21- DOWN SYNDROME
AND
KLINEFELTER’S SYNDROME
By : SEJWAL MADHUR KUMAR

2. CONTENTS
1.DOWN SYNDROME 2.KLINEFELTER
SYNDROME
 INCIDENCE
 GENETICS
 CLINICAL FEATURES
 HEMATOLOGICAL
DISORDERS
 DIAGNOSIS
 MORTALITY
• CAUSES
• CLINICAL FEATURES
• COMPLICATIONS
• INVESTIGATIONS

3. DOWN SYNDROME
Most common
chromosomal disorder
INCIDENCE
If maternal age is <20 yrs
,Approximately 1 in 1550
live births,
But if maternal age is >45
yrs ,incidence is 1 in 25 live
births

4. Genetics
 Trisomy 21 (47,XX, +21), - 94 %, The
frequency of trisomy increases with
increasing maternal age.
 Robertsonian translocation involving
chromosome 21- Approx. 3-4 %, not related
to maternal age.
 Trisomy 21 mosaicism – 1-2% cases

8. Clinical Features
 Head and neck
 Flat facial profile
 Up-slanting palpebral fissures
 Epicanthal folds
 Brushfield spots
 Flat nasal bridge
 Folded or dysplastic ears
 Open mouth
 Protruding tongue
 Short neck
 Excessive skin at the nape of
neck
 Extremities
 Short broad hands
 Short fifth finger
 Incurved fifth finger
 Transverse palmer crease
 Space between first and
second toe
 Hyper flexibility of joints

11. Mental Retardation
 Almost all DS babies have MR.
 Mildly to moderately retarded .
 Starts in the first year of life.
 Average age of sitting(11 mon), and walking (26
mon) is twice the typical age.
 First words at 18 months.
 IQ declines through the first 10 years of age,
reaching a plateau in adolescence that continues
into adulthood.

12. Heart Disease
GI Abnormalities
 50 % of Down Syndrome pts have heart disease
 Atrioventricular septal defect
 VSD
 Secundum ASD
 Mitral valve prolapse
 Valvular malformation
 GI abnormalities –in 5% cases of DS
 Duodenal atresia or stenosis
 Oesophageal atresia and intestinal stenosis

13. Hematologic disorders
 The risk of leukemia is 1 to 1.5 percent.
 65% of newborn have polycythemia resulting in
hypoglycemia.
 Risk of AML ( ACUTE MEGAKARYOBLASTIC
LUEKEMIA )is also much higher than the general
population.
 Transient leukemia.

14. Diagnosis
 Prenatal screening
 If no screening – It is recognized from the
characteristic phenotypic features.
 Confirmed by Karyotype.

15. Mortality
Median age of death has increased from 25 yrs
to 49 yrs , an average of 1.7 yrs increase per
year.
Most likely cause of death is CHD, Dementia,
Hypothyroidism and Leukemia.
Improved survival is because of increased
placements of infants in homes and
changes in treatment for common causes of
death.
Survival is better for males and blacks.

16. KLINEFELTER’S
SYNDROME

17. KLINEFELTER SYNDROME
 It is the state of male hypogonadism
due to 2 or more X chromosome with
1 or more y chromosome.
 INCIDENCE : 1 in 2000 live male
births
 KARYOTYPE: 82% have classical
47,XXY
15% mosaics , 46XY/47,XXY
Remaining polysomic individuals

18. cause
MEIOSIS 1
(GAMETOGENESIS)
NON DISJUNCTION
occurs when
homologous
chromosomes ( X and Y)
fails to separate and
producing a sperm with
extra X and Y
chromosome

19. Clinical features
 Abnormally
increased distance
between pubic ramus
and sole of feet.
 Lower body appears
abnormally
elongated also called
as EUNUCHOID
BODY HABITUS

20. CLINICAL FEATURES
 Atrophied testes - testicular biopsy shows
atrophied hyalinised seminiferous tubules
with no spermatogenesis.
 Lack of secondary sexual characteristics
 Gynecomastia is seen
 Mental intelligence is near normal
 Greater the number of X chromosome
,lower is the level of intelligence

21. COMPLICATIONS
 Infertility
 20x increased risk of ca breast
 Increased risk of germ cell tumor
 Increased risk of autoimmune
diseases like SLE (SYSTEMIC
LUPUS ERYTHEMATOSUS)

22. INVESTIGATION
 Plasma gonadotropin level
 Testicular biopsy
 Total sperm count
 karyotyping

24. THANK YOU 