Chromosomal aberrationsDefinition :-       ―Any deviation either in number or structure of the chromosomes is referred as ...
Terminologies: Diploid Hapliod Polyploidy : in multiple of ‗n‘ Aneuploidy : any number which is not exactly a multiple...
Genesis of anuploidyNon-disjunction in meiosis. Or after formation of zygote.
Structural aberrations Stable:–               - Deletions               - Translocation               - Insertion        ...
Deletion      This Involves loss of a part of chromosome.1. Terminal deletion.2. Interstitial deletion.1. Terminal deletio...
- Deletion of 5p arm- Cry of baby- Typical facial appearance- Microcephaly, hypertelorism,- Antimongoloid slant of  palpeb...
2) Interstitial deletion.       It involves two breaks and the intervening portion of  the chromosome is lost. Wilm‘s tum...
Prader- will syndrome. (15q11-13)- Inherited from father- Short stature, hypotonia- Obesity- Small hands & feet- Mild to m...
Translocation1) Robertsonian translocation- Involves two acrocentric    chromosomes-   D/G Translocation-   Also called ce...
2) Reciprocal Translocation- Exchange of material distal to  breaks- In non homologus chromosomes- No chromosome material ...
Insertion- Rare non-reciprocal type of translocation- Involves 3 breaks- 2 breaks to release fragment- 1 break to admit fr...
Inversions Pericentric – involves  both arms p & q Paracentric – either p or q Do not give abnormal  phenotype Abnorma...
Isochromosomes- Abnormal split along  the centromere- Seperation of arms- E.g. isochromosome X  (Xq)- In some cases of  Tu...
Ring chromosomes- Two breaks at terminal ends- Fusion of the cut ends- 1/5th cases of turners syndrome
Factors playing role in chromosomalaberrations   Maternal age > 35 yrs    non-disjunction during meiosis 1   Radiation  ...
Numerical aberrations Autosomal :-           Trisomy 21 / Down‘s syndrome           Trisomy 18 / Edwards syndrome        ...
Autosomal Monosomies are fetal – Abortion. Trisomies are common.
Down’s syndrome / Trisomy 21 1866 – first identified by Langdon  Down. 1959- Lejeune & associates  demonstrated extra ch...
Clinical features Mental retardation –  predominant feature IQ – 25-50 Small stature Hypotonia of muscles Brachycepha...
 Mouth is open with  protruded tongue Highly arched palate  with delayed dentition Hands are short and  broad Cardiova...
 Ears are low set and malformed
Dermatoglyphics Simian crease- classical feature Wide gap between first and second toe.
Cytogenetics Trisomy 21 (47, +21), - 94 %, The frequency of trisomy  increases with increasing maternal age. Robertsonia...
Karyotype of Down’s syndrome
Risk of Down’s syndrome Maternal age Does the couple already have baby with down’s  syndrome? What is karyotype of baby...
Diagnosis Prenatal screening If no screening – It is recognized from the  characteristic phenotypic features. Confirmed...
ManagementCounseling May begin when a prenatal diagnosis is made. Discuss the wide range of variability in manifestation...
Management cont..1. Growth – Measurements should be plotted on the  appropriate growth chart for children with DS. This w...
4. Eye disorders - An eye exam should be performed in the  newborn period or at least before 6 months of age to detect  st...
7.   Hematology – CBC with differential at birth to evaluate for     polycythemia as well as WBC.8.   Atlanto-axial instab...
Chromosomal aberrations,downs syndrome-Dr.Gourav
Chromosomal aberrations,downs syndrome-Dr.Gourav
Chromosomal aberrations,downs syndrome-Dr.Gourav
Chromosomal aberrations,downs syndrome-Dr.Gourav
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Chromosomal aberrations,downs syndrome-Dr.Gourav

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Chromosomal aberrations,downs syndrome-Dr.Gourav

  1. 1. Chromosomal aberrationsDefinition :- ―Any deviation either in number or structure of the chromosomes is referred as chromosomal aberrations‖Types :-1) Structural aberrations.2) Numerical aberrations.
  2. 2. Terminologies: Diploid Hapliod Polyploidy : in multiple of ‗n‘ Aneuploidy : any number which is not exactly a multiple of ‗n‘ 2n - 1 ------ > Turners syndrome (45X)Or 2n + 1 ------ > Down‘s syndrome (47, trisomy 21)
  3. 3. Genesis of anuploidyNon-disjunction in meiosis. Or after formation of zygote.
  4. 4. Structural aberrations Stable:– - Deletions - Translocation - Insertion - Inversions - Isochromosomes Unstable:- - Dicentric - Ring chromosomesMay occur due toa) Ionizing radiationsb) Chemical agentsc) viruses
  5. 5. Deletion This Involves loss of a part of chromosome.1. Terminal deletion.2. Interstitial deletion.1. Terminal deletion. It involves a single break and the terminal part of the chromosome is lost.e.g. cri-du-chat syndrome
  6. 6. - Deletion of 5p arm- Cry of baby- Typical facial appearance- Microcephaly, hypertelorism,- Antimongoloid slant of palpebral fissure.- Low set ears, microganthia.
  7. 7. 2) Interstitial deletion. It involves two breaks and the intervening portion of the chromosome is lost. Wilm‘s tumor with anirida. (11q13) Prader- will syndrome. (15q11-13) Angelman syndrome. (15q11-13)Microdeletion syndrome - Deletion of 3 – 4 Mb
  8. 8. Prader- will syndrome. (15q11-13)- Inherited from father- Short stature, hypotonia- Obesity- Small hands & feet- Mild to moderate mental retardation- HypogonadismAngelman syndrome. (15q11-13)- Inherited from mother- Severe mental retardation- Seizures & ataxic gaitDifference is due to genomic imprinting.
  9. 9. Translocation1) Robertsonian translocation- Involves two acrocentric chromosomes- D/G Translocation- Also called centric fusion- In 4% of down‘s cases- [50% from parents(balanced), 50% de novo in baby]
  10. 10. 2) Reciprocal Translocation- Exchange of material distal to breaks- In non homologus chromosomes- No chromosome material is lost- Abnormal production of gamets- Spontaneous abortions/ baby with congenital malformations- Carrier couple- repeated abortions.
  11. 11. Insertion- Rare non-reciprocal type of translocation- Involves 3 breaks- 2 breaks to release fragment- 1 break to admit fragment.
  12. 12. Inversions Pericentric – involves both arms p & q Paracentric – either p or q Do not give abnormal phenotype Abnormal gamets may give abnormal progeny.
  13. 13. Isochromosomes- Abnormal split along the centromere- Seperation of arms- E.g. isochromosome X (Xq)- In some cases of Turners syndrome
  14. 14. Ring chromosomes- Two breaks at terminal ends- Fusion of the cut ends- 1/5th cases of turners syndrome
  15. 15. Factors playing role in chromosomalaberrations Maternal age > 35 yrs non-disjunction during meiosis 1 Radiation correlation between radiation and non-disjunction Chromosomal abnormalities balnced translocation in parents may produce aberrations in offsprings Autoimmune disorders - not clear High titer of thyroid autoantibodies in mother associated with Down‘s syndrome in their childrens
  16. 16. Numerical aberrations Autosomal :- Trisomy 21 / Down‘s syndrome Trisomy 18 / Edwards syndrome Trisomy 13 / Patau syndrome Sex chromosome related :- Turners syndrome / 45X Polysomy X syndrome / e.g. XXX, XXXX Klinfelters syndrome / 47 XXY
  17. 17. Autosomal Monosomies are fetal – Abortion. Trisomies are common.
  18. 18. Down’s syndrome / Trisomy 21 1866 – first identified by Langdon Down. 1959- Lejeune & associates demonstrated extra chromosome no.21 Mongolism Incidence- Approximately one in 1000 live births.
  19. 19. Clinical features Mental retardation – predominant feature IQ – 25-50 Small stature Hypotonia of muscles Brachycephaly with flat occiput Epicanthal fold—mongoloid slant Flat nose, low nasal bridge
  20. 20.  Mouth is open with protruded tongue Highly arched palate with delayed dentition Hands are short and broad Cardiovascular defect in 1/10th cases.
  21. 21.  Ears are low set and malformed
  22. 22. Dermatoglyphics Simian crease- classical feature Wide gap between first and second toe.
  23. 23. Cytogenetics Trisomy 21 (47, +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 – 2 to 3 % cases
  24. 24. Karyotype of Down’s syndrome
  25. 25. Risk of Down’s syndrome Maternal age Does the couple already have baby with down’s syndrome? What is karyotype of baby?(typical / translocation) Parent carrier of translocation?
  26. 26. Diagnosis Prenatal screening If no screening – It is recognized from the characteristic phenotypic features. Confirmed by Karyotype.( chorionic villous biopsy , amniocentesis)
  27. 27. ManagementCounseling May begin when a prenatal diagnosis is made. Discuss the wide range of variability in manifestation and prognosis. Medical and educational treatments and interventions should be discussed. Initial referrals for early intervention, informative publications, parent groups, and advocacy groups.
  28. 28. Management cont..1. Growth – Measurements should be plotted on the appropriate growth chart for children with DS. This will help in prevention of obesity and early diagnosis of celiac disease and hypothyroidism.2. Cardiac disease – All newborns should be evaluated by cardiac ECHO for CHD in consultation with pediatric cardiologist.3. Hearing – Screening to be done in the newborn period, every 6 months until 3 yrs of age and then annually.
  29. 29. 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.
  30. 30. 7. Hematology – CBC with differential at birth to evaluate for polycythemia as well as WBC.8. Atlanto-axial instability – X ray for evidence of AAI or sub- luxation at 3 to 5 years of age.9. Alzheimer‘s disease – Adult with a Down Syndrome has earlier onset of symptoms. When diagnosis is considered, thyroid disease and possible depression should be excluded.

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