TRISOMY 21- DOWN SYNDROMEAND

KLINEFELTER’S SYNDROME

By : SEJWAL MADHUR KUMAR

CONTENTS 1.DOWN SYNDROME 2.KLINEFELTER

SYNDROME INCIDENCE

GENETICS

CLINICAL FEATURES

HEMATOLOGICAL DISORDERS

DIAGNOSIS

MORTALITY

• CAUSES • CLINICAL FEATURES• COMPLICATIONS• INVESTIGATIONS

DOWN SYNDROME

INCIDENCEIf 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

Most common

chromosomal disorder

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

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

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.

Heart DiseaseGI 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

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.

Diagnosis

Prenatal screening

If no screening – It is recognized from the characteristic phenotypic features.

Confirmed by Karyotype.

MortalityMedian 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.

KLINEFELTER’S SYNDROME

KLINEFELTER SYNDROME

It is the state of male hypogonadismdue 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

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

Clinical features

Abnormally increased distance between pubic ramus and sole of feet.

Lower body appears abnormally elongated also called as EUNUCHOID BODY HABITUS

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

COMPLICATIONS

Infertility

20x increased risk of ca breast

Increased risk of germ cell tumor

Increased risk of autoimmune diseases like SLE (SYSTEMIC LUPUS ERYTHEMATOSUS)

INVESTIGATION

Plasma gonadotropin level

Testicular biopsy

Total sperm count

karyotyping

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