TRISOMY 21- DOWN SYNDROME

TRISOMY 21- DOWN SYNDROME andklinefelters syndromeBy : SEJWAL MADHUR KUMAR

CONTENTS 1.DOWN SYNDROME 2.KLINEFELTER SYNDROME

INCIDENCEGENETICSCLINICAL FEATURESHEMATOLOGICAL DISORDERSDIAGNOSISMORTALITYCAUSES CLINICAL FEATURESCOMPLICATIONSINVESTIGATIONSDOWN SYNDROME

IncidenceIf maternal age is 45 yrs ,incidence is 1 in 25 live births

Most common chromosomal disorderGeneticsTrisomy 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 FeaturesHead and neckFlat facial profileUp-slanting palpebral fissuresEpicanthal foldsBrushfield spotsFlat nasal bridgeFolded or dysplastic earsOpen mouthProtruding tongueShort neck Excessive skin at the nape of neckExtremitiesShort broad handsShort fifth fingerIncurved fifth fingerTransverse palmer creaseSpace between first and second toeHyper flexibility of joints

Mental RetardationAlmost 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 Abnormalities50 % of Down Syndrome pts have heart diseaseAtrioventricular septal defectVSDSecundum ASDMitral valve prolapse Valvular malformationGI abnormalities in 5% cases of DS Duodenal atresia or stenosisOesophageal atresia and intestinal stenosis

Hematologic disordersThe 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. DiagnosisPrenatal screeningIf 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 andchanges in treatment for common causes of death.

Survival is better for males and blacks.KLINEFELTERS SYNDROMEKLINEFELTER SYNDROMEIt 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 birthsKARYOTYPE: 82% have classical 47,XXY 15% mosaics , 46XY/47,XXYRemaining polysomic individualscause

MEIOSIS 1 (GAMETOGENESIS)

NON DISJUNCTION occurs when homologous chromosomes ( X and Y) fails to separate and producing a sperm with extra X and Y chromosomeClinical features

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

CLINICAL FEATURESAtrophied testes - testicular biopsy shows atrophied hyalinised seminiferous tubules with no spermatogenesis.Lack of secondary sexual characteristicsGynecomastia is seenMental intelligence is near normalGreater the number of X chromosome ,lower is the level of intelligenceCOMPLICATIONSInfertility20x increased risk of ca breastIncreased risk of germ cell tumorIncreased risk of autoimmune diseases like SLE (SYSTEMIC LUPUS ERYTHEMATOSUS)INVESTIGATIONPlasma gonadotropin levelTesticular biopsyTotal sperm countkaryotyping

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