Chromosomal Disorders.ppt
- 1. WWW.SMSO.NET Chromosomal Disorders Chromosomal Disorders Done By : Done By : Dr.Ibsa A Dr.Ibsa A
- 2. WWW.SMSO.NET Chromosomal Abnormalities Chromosomal Abnormalities Numeric Autosomal abnormalities Numeric Autosomal abnormalities Structural Autosomal abnormalities Structural Autosomal abnormalities Sex Chromosome abnormalities Sex Chromosome abnormalities Single Gene defect Single Gene defect
- 3. WWW.SMSO.NET Numeric Autosomal abnormalities Numeric Autosomal abnormalities Trisomy 21(Down Syndrome) Trisomy 21(Down Syndrome)
- 4. WWW.SMSO.NET Structural Autosomal abnormalities Structural Autosomal abnormalities Deletions Deletions cri du chat syndrome cri du chat syndrome (5p) (5p) Robertsonian Translocation Robertsonian Translocation Trisomy 21,14 Trisomy 21,14 Reciprocal translocation Reciprocal translocation Partial Partial monosomy & partial trisomy will monosomy & partial trisomy will result result Mosaicism Mosaicism 2 distinct cell lines in the 2 distinct cell lines in the sane individual sane individual
- 5. WWW.SMSO.NET Sex Chromosome abnormalities Sex Chromosome abnormalities Turner syndrome Turner syndrome Klinefelter syndrome(47,XXY) Klinefelter syndrome(47,XXY) Extra Y chromosome Extra Y chromosome (48,XYYY), (48,XYYY), (49,XYYYY) (49,XYYYY)
- 6. WWW.SMSO.NET Single Gene defect Single Gene defect Autosomal Dominant Autosomal Dominant Autosomal Recessive Autosomal Recessive X-linked Dominant X-linked Dominant X- linked Recessive X- linked Recessive Multifactorial Inheritence Multifactorial Inheritence
- 7. WWW.SMSO.NET Single Gene defect Single Gene defect Autosomal Dominant Autosomal Dominant Marfan syndrome Marfan syndrome Neurofibromatosis Neurofibromatosis Von willebrand disease Von willebrand disease
- 8. WWW.SMSO.NET Single Gene defect Single Gene defect Autosomal Recessive Autosomal Recessive Cystic fibrosis Cystic fibrosis Hemochromatosis Hemochromatosis Sickle-cell anemia Sickle-cell anemia
- 9. WWW.SMSO.NET Single Gene defect Single Gene defect X-linked Dominant X-linked Dominant Vit D resistant Rickets Vit D resistant Rickets X- linked Recessive X- linked Recessive Fragile X syndrome Fragile X syndrome G6PD deficiency G6PD deficiency Multifactorial Inheritence Multifactorial Inheritence Congenital heart disease Congenital heart disease
- 10. WWW.SMSO.NET Down Syndrome Down Syndrome syndrome of mental handicap associated syndrome of mental handicap associated with various physical abnormalities and a with various physical abnormalities and a supposed resemblance to members of the supposed resemblance to members of the Mongol race Mongol race This condition is now known as Down's This condition is now known as Down's syndrome or trisomy 21 syndrome or trisomy 21 Down's syndrome is the commonest of the Down's syndrome is the commonest of the chromosomal disorders and a major cause of chromosomal disorders and a major cause of mental retardation. mental retardation. The incidence is approximately 1 in 600 The incidence is approximately 1 in 600 births. births.
- 11. WWW.SMSO.NET Clinical Features Clinical Features Patients tend to have a characteristic Patients tend to have a characteristic appearance with a typical face: appearance with a typical face: brachycephaly brachycephaly short neck short neck epicanthic folds on the medial aspect of the eyes epicanthic folds on the medial aspect of the eyes an inward down - mongoloid - slant to the eyes an inward down - mongoloid - slant to the eyes Brushfield spots on the iris Brushfield spots on the iris almond shaped eyes almond shaped eyes small simple ears, which may be low set small simple ears, which may be low set flat nasal bridge flat nasal bridge protruding tongue, mouth hanging open protruding tongue, mouth hanging open narrow high arched palate narrow high arched palate
- 12. WWW.SMSO.NET Clinical Features Clinical Features Other features include : Other features include : hypotonia, often noted at birth hypotonia, often noted at birth short fingers and especially short or absent second short fingers and especially short or absent second phalanx in the fifth digit phalanx in the fifth digit transverse tongue fissures transverse tongue fissures congenital heart lesions congenital heart lesions mental retardation, with a majority having an IQ less mental retardation, with a majority having an IQ less than 50 than 50 single, simian crease in about 45% single, simian crease in about 45% wide space between first and second toes wide space between first and second toes straight pubic hair straight pubic hair cataract in 60% of patients cataract in 60% of patients
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- 18. WWW.SMSO.NET Associations Associations Down's syndrome is associated with a Down's syndrome is associated with a higher incidence of a variety of congenital higher incidence of a variety of congenital abnormalities, including: abnormalities, including: duodenal atresia in 10% duodenal atresia in 10% Hirschsprung's disease in 3% Hirschsprung's disease in 3% other intestinal atresias other intestinal atresias
- 19. WWW.SMSO.NET Associations Associations Up to 40% of cases are born with congenital heart Up to 40% of cases are born with congenital heart defects, including: defects, including: atrioventricular canal - the most common major defect atrioventricular canal - the most common major defect ventricular septal defect ventricular septal defect patent ductus arteriosus patent ductus arteriosus atrial septal defect - ostium primum in 40% atrial septal defect - ostium primum in 40% tetralogy of Fallot tetralogy of Fallot Rarer associations include: Rarer associations include: annular pancreas annular pancreas increased incidence of sensorineural deafness increased incidence of sensorineural deafness
- 20. WWW.SMSO.NET Complications Complications recurrent upper respiratory tract infection recurrent upper respiratory tract infection hypothyroidism hypothyroidism acute lymphoblastic leukaemia acute lymphoblastic leukaemia the risk of solid tumours is reduced the risk of solid tumours is reduced Atlantoaxial instability (C1–C2 Atlantoaxial instability (C1–C2 subluxation subluxation
- 21. Con’t Con’t Increased Risk for Development of Increased Risk for Development of Leukemia:AML, ALL Leukemia:AML, ALL Myelodysplasia Myelodysplasia Transient lymphoproliferative syndrome Transient lymphoproliferative syndrome Celiac disease Celiac disease Hypothyroidism Hypothyroidism Diabetes mellitus Diabetes mellitus Obesity Refractive errors & Strabismus Obesity Refractive errors & Strabismus Mitral valve prolapse Mitral valve prolapse Conductive and/or sensorineural hearing loss Conductive and/or sensorineural hearing loss Obstructive sleep apnea Obstructive sleep apnea Epilepsy Epilepsy Alzheimer disease Alzheimer disease ADHD ADHD WWW.SMSO.NET
- 22. WWW.SMSO.NET Prognosis Prognosis 90% of people with Down's syndrome 90% of people with Down's syndrome survive to five years of age, the remaining survive to five years of age, the remaining 10% dying as a result of congenital heart 10% dying as a result of congenital heart disease, Hirschprung's disease and disease, Hirschprung's disease and infection. infection. Half of people with Down's syndrome Half of people with Down's syndrome reach 60 years old, which may place a reach 60 years old, which may place a considerable burden of care on family. considerable burden of care on family.
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- 24. WWW.SMSO.NET Edwards syndrome Edwards syndrome There are 23 pairs of human There are 23 pairs of human chromosomes. In Trisomy 18 (Edwards chromosomes. In Trisomy 18 (Edwards syndrome), there is an extra chromosome syndrome), there is an extra chromosome with the 18th pair. Like Trisomy 21 (Down with the 18th pair. Like Trisomy 21 (Down syndrome), Trisomy 18 affects all systems syndrome), Trisomy 18 affects all systems of the body and causes distinct facial of the body and causes distinct facial features . features .
- 25. WWW.SMSO.NET EDWARDS syndrome EDWARDS syndrome Incidence: Incidence: Trisomy 18 affects approximately 1 in Trisomy 18 affects approximately 1 in 8000 neonates . 8000 neonates . Male : female ------------- Male : female ------------- 1:3 1:3 There is weak association with advanced There is weak association with advanced maternal age. maternal age. 25% are conceived by mothers aged 35 25% are conceived by mothers aged 35 years or over. years or over.
- 26. WWW.SMSO.NET Clinical features Clinical features Generally: Generally: IUGR IUGR Sever FTT Sever FTT MR MR
- 27. WWW.SMSO.NET c/p c/p Craniofacial: Craniofacial: Prominent occiput Prominent occiput Low-set dysplastic Low-set dysplastic ears ears Short narrow Short narrow palpebral fissures palpebral fissures Small mouth , small Small mouth , small jaw jaw
- 28. WWW.SMSO.NET C/p C/p Limbs: Limbs: Clenched hands with Clenched hands with 2 2ND ND and 5 and 5th th fingers fingers overlapping 3 overlapping 3rd rd and 4 and 4th th fingers fingers Small nails especially Small nails especially on 5 on 5th th finger finger short dorsiflexed big short dorsiflexed big toe toe Rocker-bottom feet Rocker-bottom feet
- 30. WWW.SMSO.NET c/p c/p Others: Others: Congenital heart disease Congenital heart disease Esophageal atresia Esophageal atresia Tracheo-esophageal fistula Tracheo-esophageal fistula Spina bifida Spina bifida
- 31. WWW.SMSO.NET Dx Dx Before birth, ultrasound can detect Before birth, ultrasound can detect abnormalities in the fetus. abnormalities in the fetus. Genetic testing by amniocentesis before Genetic testing by amniocentesis before birth or blood test after birth can confirm birth or blood test after birth can confirm the diagnosis. the diagnosis. Ultrasounds of the heart and abdomen can Ultrasounds of the heart and abdomen can detect abnormalities, as can x-rays of the detect abnormalities, as can x-rays of the skeleton skeleton
- 32. WWW.SMSO.NET treatment treatment Medical care for individuals with Trisomy Medical care for individuals with Trisomy 18 is supportive, and focuses on providing 18 is supportive, and focuses on providing nutrition, treating infections, and managing nutrition, treating infections, and managing heart problems. heart problems. During the first months of life, infants with During the first months of life, infants with Trisomy 18 require skilled medical care. Trisomy 18 require skilled medical care. Advances in medical care over time will, in Advances in medical care over time will, in the future, help more infants with Trisomy the future, help more infants with Trisomy 18 live into childhood and beyond 18 live into childhood and beyond
- 33. WWW.SMSO.NET prognosis prognosis 50% die within 1 50% die within 1st st week week Most of the cases die by age of one year Most of the cases die by age of one year Surviving infants and children show sever Surviving infants and children show sever retardation of growth and development retardation of growth and development
- 34. Trisomy 13 Trisomy 13 Sever developmetal retardation Sever developmetal retardation Incidence 1/20000 Incidence 1/20000 90% dead in the 1 90% dead in the 1st st year year Midline brain defect Midline brain defect Malformed ear Malformed ear Microophalmos and coloboma Microophalmos and coloboma Scalp defect Scalp defect
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- 37. Turner syndrome Turner syndrome Is due to partial or complete absence of 2 Is due to partial or complete absence of 2nd nd x-chrom. with or x-chrom. with or without mocism without mocism Single x-chrom. Maternal in origin in 80%. Single x-chrom. Maternal in origin in 80%. Risk does not increase with maternal age Risk does not increase with maternal age Mechanism of chrom. Loss is not known. Mechanism of chrom. Loss is not known. 50% of pts are 45,x chrom.complet,15% are mosacism 50% of pts are 45,x chrom.complet,15% are mosacism Occur in 1 in 1,500 to 2500 live birth female Occur in 1 in 1,500 to 2500 live birth female 99% case are aborted at conception. 99% case are aborted at conception. c/m c/m At birth At birth oedema of the dorsum of the hand and feet oedema of the dorsum of the hand and feet Skin fold at the nape of the neck Skin fold at the nape of the neck low birth weight and short stature low birth weight and short stature
- 38. Con’t Con’t During childhood During childhood webbing neck* webbing neck* Small mandible Small mandible low posterior hair line* low posterior hair line* Broad chest and wide spaced nipple* Broad chest and wide spaced nipple* Epicantal fold and high arched palate Epicantal fold and high arched palate Cubital valgus,hyperconvex finger nails Cubital valgus,hyperconvex finger nails Short stature* Short stature* Delayed sexual maturation Delayed sexual maturation Associated defects or complications Associated defects or complications cardiac(bicuspid aortic valve,coa,mv prolapse,APVR) cardiac(bicuspid aortic valve,coa,mv prolapse,APVR) Renal(pelvic or horseshoe kidney, double collecting system,UPJ obst. etc Renal(pelvic or horseshoe kidney, double collecting system,UPJ obst. etc Gonadal failure(but 10-20% may develop breast and few have menses Gonadal failure(but 10-20% may develop breast and few have menses Increased risk of miscarriage and offspring with trysomy 21. Increased risk of miscarriage and offspring with trysomy 21.
- 39. Con’t Con’t Recurrent OM(75%)-sensory neural hearing loss Recurrent OM(75%)-sensory neural hearing loss Scoliosis, congenital hip dysplasia Scoliosis, congenital hip dysplasia Intelligence is usually normal Intelligence is usually normal IBD,GI bleeding IBD,GI bleeding Associated other autoimmune disorders Associated other autoimmune disorders Abn. CH Abn. CH2 2O metabolism, insulin resistance, glucose intolerance O metabolism, insulin resistance, glucose intolerance Increased blood pressure Increased blood pressure Skeletal Abn.(shortening of 4 Skeletal Abn.(shortening of 4th th metatarsal & metacarpal bones, epiphseal metatarsal & metacarpal bones, epiphseal dysgenesis of elbow & knee joint, inadequate mineralization, scoliosis) dysgenesis of elbow & knee joint, inadequate mineralization, scoliosis) Lab Ix Lab Ix Chrom. And DNA analysis Chrom. And DNA analysis U/S of kidneys, ovaries heart etc. U/S of kidneys, ovaries heart etc. Skeletal study Skeletal study FSH(increased to greater than age matched level during infancy and FSH(increased to greater than age matched level during infancy and puberty) puberty) Thyroid peroxidase Ab. Thyroid peroxidase Ab.
- 40. Con’t Con’t mx mx rhGH rhGH Estrogen & conjugate estrogen replacement at 12-13yrs may induce Estrogen & conjugate estrogen replacement at 12-13yrs may induce puberty puberty Genetic counselling Genetic counselling Psychosocial support Psychosocial support
- 41. Klinefelter syndrom Klinefelter syndrom Is most commen chro.aneuploidy in male Is most commen chro.aneuploidy in male Due to abn.meiotic nondysjunction of x-chrom. During Due to abn.meiotic nondysjunction of x-chrom. During parental gametogenesis parental gametogenesis Most common chrom. Abn is (47,xxy) in 80% of case, Most common chrom. Abn is (47,xxy) in 80% of case, some have mosaic pattern like46xy/xxy etc some have mosaic pattern like46xy/xxy etc Extra x-chrom.is 54%maternal,46% paternal in origin Extra x-chrom.is 54%maternal,46% paternal in origin Increased risk with advanced maternal age Increased risk with advanced maternal age Occur in 1 in500live born male Occur in 1 in500live born male Accounts for 1%of mentally retarded & psychiatric Accounts for 1%of mentally retarded & psychiatric pts,3% of infertile male,5-10% of pt with oligospermia or pts,3% of infertile male,5-10% of pt with oligospermia or azoospermia azoospermia. .
- 42. Con’t Con’t c/m c/m Rarely diagnosed before puberty b/c of subtle c/m in children Rarely diagnosed before puberty b/c of subtle c/m in children Should be suspected in all children with mental Should be suspected in all children with mental retardation,psychosocail,learning & school adjustment problems. retardation,psychosocail,learning & school adjustment problems. Children are anxious,immature,excessively shy or aggressive Children are anxious,immature,excessively shy or aggressive Verbal defects, underachievement in reading, spelling & Verbal defects, underachievement in reading, spelling & mathematics mathematics Developmental delay Developmental delay Thin, tall, slim, long legs,undeweight are xics Thin, tall, slim, long legs,undeweight are xics Small test,hypospadia & crypto orchidism, Small phallus Small test,hypospadia & crypto orchidism, Small phallus Arrest in spermatogenesis, antisperm Ab Arrest in spermatogenesis, antisperm Ab Gynecomastia in 80% of cases Gynecomastia in 80% of cases Increased risk of pulm.diseae, leukaemia, lymphoma and Increased risk of pulm.diseae, leukaemia, lymphoma and carcinomas like breast ca and germ cell tumors carcinomas like breast ca and germ cell tumors MR is high 2ry to pulm.embolism,DM ,epilepsy MR is high 2ry to pulm.embolism,DM ,epilepsy
- 44. Con’t Con’t Lab Lab Chrom analysis Chrom analysis FSH & LH are normal before 10yrs of age FSH & LH are normal before 10yrs of age Elevated stradiol Elevated stradiol Response to GnSH& to hCG is normal Response to GnSH& to hCG is normal By midpuberty By midpuberty testicular growth stops testicular growth stops gonadotropins elevated gonadotropins elevated decrease in inhibin B hormon decrease in inhibin B hormon Testicular bx Testicular bx absence of germcells absence of germcells Halinization of semeniferous tubles Halinization of semeniferous tubles Edematous lydig cells Edematous lydig cells Sertoli cell predominance Sertoli cell predominance Oligo- or azoospermia Oligo- or azoospermia MRI-reduction in lt temporal lobe grey matter volume MRI-reduction in lt temporal lobe grey matter volume
- 45. Con’t Con’t Mx Mx Suportive Suportive Genetic counselling Genetic counselling Long acting testestron after 11-12yrs of age Long acting testestron after 11-12yrs of age Prognosis Prognosis o Mental retardation is common Mental retardation is common o In most pts,most testicular sperm(94%) have In most pts,most testicular sperm(94%) have normalm pattern of sex chrom seggregation normalm pattern of sex chrom seggregation o Some pts have adequate sperm &have resulted Some pts have adequate sperm &have resulted in normal live birth in normal live birth o