• He trained at the London Hospital. • He was the first to recognize what he called “Mongolian idiocy” as a syndrome, a “throwback” to a “lower” race. • The children appeared similar, like brothers and sisters. • The disorder became known as “Mongolism.”John Langdon • It is now called Down Down syndrome. • He opposed slavery, and 1828-1896 argued this “ throwback” • disproved the “Negroid race” was inferior. • He advocated equal education for women.
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Table 1: Incidence of Down SyndromeMaternal Age- Specific Risk for Trisomy -21 at livebirth Age (years) Incidence 20 1 in 1500 30 1 in 900 35 1 in 350 40 1 in 100 41 1 in 70 42 1 in 55 43 1 in 40 44 1 in 30 45 1 in 25
Trisom %, T my 21 (4 h triso e freque 7, +21), - t ic s my i incre ncre ncy of 95G en e asing ases w Robe mate r n al ith trans rtson age. ia n chro location moso invol 3 %, v mate not r me 21- A ing e r nal lated to pprox. Trisom age. 2% y 21 case mosai s cism –
Table 2. Karyotyping in Down syndromeNon-disjunction trisomy21Robertsonian 3%TranslocationMosaicism Recurrence Risk by 2% KaryotypeNondisjunction Trisomy47(XX or XY) + 21 1%Translocation onboth parents normal <1%other carrier 10%father carrier 2.5%either parent t(21q;21q) 100%Mosaics <1%
Trisomy 21 in Down Syndrome24,X 23,Y+21 Sperm, normal Egg, extra 21 47,XY,+21 Zygote
Clinical Features Head and neck Extremities Brachycephaly Short broad hands Up-slanting palpebral fissures Short fifth finger Epicanthal folds Incurved fifth finger Brushfield spots Transverse palmer crease Flat nasal bridge Space between first and Folded or dysplastic ears second toe Open mouth Hyper flexibility of joints Protruding tongue Short neck Life expectancy : 55 years Excessive skin at the nape of neck (National Down Syndrome Society)
Neon Flat facial profile Neon Poor Moro reflex Excessive skin at at al f at al f the nape of neck Slanted palpebral Dysplasia of pelvis fissures eatu eatur Hypotonia Anomalous ears Hyper flexibility of Dysplasia of of fifth res joints midphalanx es finger Transverse palmer crease
Newborn• cardiac defects (50% ): AVSD [mostcommon], VSD, ASD, TOF or PDA• gastrointestinal (12%): duodenal atresia[commonest], tracheo-oesophagealfistula, anorectal malformation, pyloricstenosis and Hirshsprung disease.• vision: congenital cataracts (3%),glaucoma.• hypotonia & joint laxity• feeding problems. UsuallyResolve in few weeks.• congenital hypothyroidism (1%)• congenital dislocation of the hips
Infancy and Childhood• delayed developmental milestones• mild to moderate intellectualimpairment (IQ 25 to 50)• seizure disorder (6%)• recurrent respiratory infections• hearing loss (>60%) due to secretory otitis media,sensorineural deafness,or both• visual Impairment – squint (50%), cataract (3%),nystagmus (35%), glaucoma,refractive errors (70%)• sleep related upper airway obstruction. Oftenmultiple factorial.• leukaemia (relative risk:15 to 20 times). Incidence1%
• atlantoaxial instability. Symptoms of spinal cordcompression include neck pain,change in gait, unusual posturing of the head andneck (torticollis), loss of upper body strength, abnormal neurological reflexes,and change in bowel/bladderfunctioning.• hypothyroidism (10%). Prevalence increaseswith age• short stature – congenital heart disease, sleeprelated upper airway obstruction,coeliac disease, nutritional inadequacy due tofeeding problems and thyroidhormone deficiency may contribute to this• over/underweight
• Epicanthal folds are prominent • The iris has the light smudgy opacities of Brishfield spotsWhich eyes belong to a child with Down syndrome?
Adolescence and Adulthood• puberty - in Girls menarche is onlyslightly delayed. Fertility presumed- in Boys are usually infertile due to lowtestosterone levels• increased risk of dementia /Alzheimerdisease in adult life• shorter life expectancy
BW, le less ngth an in DS d HC Redu are th ced Preva growth raG row grea lence of ter in obes te Weig DS ity is expe ht is less infan cted for than ts wi leng incre th D S th in ally s ases disp , and the obes o that th roportio n e by ey ar n age e 3-4 y ears
Diagnosis Prenatal screening-"triple screen" can be done between the15th and the 20th weeks of pregnancy.1. Alpha-fetoprotein2. Unconjugated Estriol3. Human Chorionic Gonadotropin (hCG)-PAPP-A, which stands for pregnancy-associated plasma protein A Confirmed by Karyotype. 47,XX,21 21q21q translocation,
Tests for positive results If the prenatal screening is positive or are at a high risk for Down syndrome, do further testing.Amniocentesis Chorionic villus Percutaneous• Done in midtrismester sampling (CVS) umbilical bloodbetween 15 and 18 weeks of • Sample is taken by needle sampling (PUBS)gestation. About 20 ml of biopsy under ultrasound • To exam for chromosomalamniotic fluid withdrawn guidance. Advantage of this defects, blood is takenfor diagnostic studies. method is it can be taken from the vein in theUsually taken in pregnant earlier than Amniocentesis, umbilical cord.woman above 35 years old usually between 10 and 12 •This test has a greater riskor older at the time of weeks of gestation. for miscarriage than bothdelivery. • 1% risk of spontaneous Amniocentesis and CVS.• risk of miscarriage is 1 in • Test usually is only done if miscarriage300 completely necessary.
Management1. Growth – Measurements should be plotted on the appropriate growth chart for children with DS. This will help in preventionandobesity and early diagnosis of celiac disease of hypothyroidism.2. Cardiac disease – All newborns should be evaluated by cardiac ECHO by 2 weeks (if clinical examination or ECG were abnormal) or 6 weeks.3. Hearing – Screening to be done in the newborn period, every 6 months until 3 years of age and then annually.
Management (cont.)4. Eye disorders - An eye exam should be performed in the newborn period or at least before 6 months of age to detect strabismus, nystagmus, and cataracts.5. Thyroid Function – Should be done in newborn period and should be repeated at six and 12 months , and then annually.6. Celiac Disease – Screening should begin at 2 yrs. Repeat screening if signs/Sx develop.
Management ( cont)7. Hematology – CBC with differential at birth to evaluate for polycythemia as well as WBC.8. Atlanto-axial instability – X ray (14% in patient) for evidence of AAI or sub-luxation at 3 to 5 years of age.; symptomatic in 1-2%. small risk for major neurological damage but cervical spine X rays in children have no predictive validity for subsequent acute dislocation/ subluxation at the atlantoaxial joint children with Down’s syndrome should not be barred from taking part in sporting activities
Appropriate care of the neckwhile under general anasthesiaor after road traffic accident isadvisable
TABLE 3Incidence of Some Associated Medical Complications in Personswith Down Syndrome Disorder Incidence (%) Mental retardation > 95 Growth retardation > 95 Early Alzheimers disease Affects 75% by age 60 Congenital heart defects 40 (atrioventricular canal defect, ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot) Hearing loss (related to otitis media 40 to 75 with effusion or sensorineural) Ophthalmic disorders (congenital 60 cataracts, glaucoma, strabismus) Epilepsy 5 to 10 Gastrointestinal malformations 5 (duodenal atresia, Hirschsprung disease) Hypothyroidism 5 Leukemia 1 Atlantoaxial subluxation with spinal <1 cord compression Increased susceptibility to infection Unknown (pneumonia, otitis media, sinusitis, pharyngitis, periodontal disease) Infertility > 99% in men; anovulation in 30% of women
MortalityMedian age of death has increased from 25 yrs in1983 to 49 yrs in 1997, an average of 1.7 yrsincrease per year.Most likely cause of death is CHD, Dementia,Hypothyroidism and Leukemia.Improved survival is because of increasedplacements of infants in homes andchanges in treatment for common causes of death.Survival is better for males and blacks.
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Famous people with Down syndrome Chris Burke Jane Cameron Sujeet Desai Bernadette Resha
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