Down's syndrome is associated with mental retardation. Which of the following abnormalities are not found in Down's syndrome?
Ans. a. Deletion 21 (Ref: Robbins 9 epi61. 8'c pi611Deletion of chromosome number 21 is not seen in Down's syndrome."Approximately 95% of Down's syndromes have trisomy 21, so their chromosome count is 47. Studies in which DMA polymorphisms were used to trace the parental origin of chromosome 21. the extra chromosome is of maternal origin. In about 4% of cases of Down syndrome, the extra chromosomal material derives from the presence of a robertsonian translocation of the long arm of chromosome 21 to another acrocentric chromosome (e.g., 22 or 14). Approximately 1% of Down syndrome patients are mosaics, usually having a mixture of cells with 46 and 47 chromosomes. "Down s Syndrome (Trisomy 21)* It is the \1C of the chromosomal disorders^ and a major cause of mental retardation* Mitotic non-disjunction is responsible for development of mosaicism. Genetics of Down syndrome Meiotic NondisjunctionRobertsonian translocationMosaicism* Seen in 95% cases with trisomy 21.* MC cause of Down syndrome* Extra chromosome is of maternal origin.* Strong relation with maternal age* Seen in about 4% of cases of Down syndrome.* Extra chromosomal material derives from the presence of a robertsonian translocation of the long arm of chromosome 21 to another acrocentric chromosome (e.g., 22 or 14).* Most cases are (but not always} familial.* No relation with maternal age* Seen in -1% of Down syndrome patients* Results from mitotic nondisjunction of chromosome 21 during an earfy stage of embryogenesis.* Patients have a mixture of cells with 46 and 47 chromosomes (mosaicism).* No relation with maternal age. Features of Down Syndrome (My Child has Problem)* Mental retardation/Micrognathia* Congenital heart disease/Cataracts.Clinodactyly* Hypotonia/Hypothyroidism* Increased gap between 1st and 2nd toe (Sandle toe)* Leukemia risk/Lung problem (Increased risk of respiratory tract infections)* Duodenal atresia* Hirschsprung's disease/Hearing loss* Alzheimer's disease/Atlantoaxial instability* Simian crease (Single palmar fold)* Protruding tongue* Round face/Roliing eye (nystagmus)* Occi put flat'Oblique pa Ipebrai fissure (mongoloid slant)* Brushfteld spot/Brachycephaly* Low nasal bridge,'Language problem* E pica nthic fold/Ear foldedMongolian slant/MyoclonusComplications of Down's syndrome* Congenital cardiac defects (NIC is VSD)* Increased risk of leukemia particularly ALL (more commonly) and specifically the megakaryoblastic form of AML (M7-AML)* Hypothyroidism* Reduced fertility in females (Males are totally infertilejl* Increased risk of respiratory tract infections First and second trimester Down syndrome screensScreenPerformed atDetection rateFalse positiveDescriptionTriple test15-20 weeks70%5%Maternal serum AFP (Low) + Estriol (Low) + hCG (High)Quad screen15-20 weeks81%5%Triple test + Inhibin-alpha (High)First trimester combined test10-13 weeks85%5%Ultrasound to measure:Nuchal translucency (Increased)Ductus venosus flow (reversed)Nasal bone (hypoplasia)+ hCG + Pregnancy associated plasma protein A, PAPPA (Low)Integrated test10-13 weeks and15-20 weeks95%5%Measurements from both,the 1st trimester combined test and 2nd trimester Quad test to yield a more accurate screening result
Deletion 21
Trisomy 21
Translocation t (13,21), t (21,21)
Mosaic 21
Genetic Approach to Pediatric Medicine