Clinical and cytogenetic profile of Down syndrome at King Hussein Medical Centre

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Clinical and cytogenetic profile of Down syndrome
at King Hussein Medical Centre

• Wajdi Amayreh, MB BS, MRCPCH,
• Kefah Al Qa'qa', MD, Ali Al Hawamdeh, MD,FRCPCH,
• Samah Tawalbeh, RN

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Down syndrome

• It is caused by triplicate state (trisomy) of all
  or a critical portion of chromosome 21
• The most common autosomal trisomy
• The most common genetic cause of severe learning
  difficulties
• Incidence in live-born infants is 1 in 600 to 1
  in 1000
• Suspected at birth because of babys facial
  appearance difficult to acertain!
• Chromosomal analysis is needed to
• confirm the diagnosis
• determine the risk of recurrence
• for genetic counselling

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Clinical features

• Round face, bracycephaly, flat facial profile,
  epicanthic folds, brushfield spots in iris,
  protruding tongue, small low set ears, excessive
  skin at the nape of the neck
• Semian creases, short broad hands, clinodactaly,
  abnormal dermatoglyphics, and sandal gap are
  helpful diagnostic features

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Other clinical features and problems

• Hypotonia
• Congenital heart defects
• GIT anomalies Dudenal atresia, Hirshsprung
  disease, anorectal anomalies, etc.
• Mental retardation and severe learning
  difficulties
• Hpothyroidism
• Small stature
• Recurrent respiratory infections
• Hearing impairment
• Visual impairment cataracts, squints, etc.
• Increased risk of leukaemia
• Risk of atlantoaxial instability
• Alzheimers disease

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Cytogenetics

• Non-disjunction
• Most errors occur at meiosis
• The pair of chromosome 21 fail to separate one
  gamete has 2 chromosmes 21 and one has none
• The incidence of trisomy 21 due to
  non-disjunction rises with increasing maternal
  age
• Many cases are born to younger mothers
• Screening tests are available to detect an
  increased risks of Down syndrome
• After having one child with trisomy 21 due to
  non-disjunction, the risk of recurrence of Down
  syndrome is 1 in 200 under 35 years and twice the
  age-specific risk at and above 35 years

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Cytogenetics

• Translocation
• A chromosome 21 is translocated onto a
  chromosome 14 or more rarely 15, 22 or 21 and is
  known as Robertsonian translocation
• In about one quarter of these, one parent has a
  balanced translocation, appearing to have only 45
  chromosomes, one chromosome 21 is attached to
  another chromosome
• The risk of recurrence is 10-15 if the mother is
  the translocation carrier and about 2.5 if the
  father is the carrier
• If a parent carries the rare 2121 translocation,
  all the offspring will have Down syndrome
• If neither parent carries a translocation, the
  risk of recurrence is lt1

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Cytogenetics

• Mosaicism
• Some of the cells are normal and some have
  trisomy 21
• Usually after the formation of the zygote, but
  non-disjunction at mitosis
• The phenotype may be milder in mosaicism
• The chromosomes of a baby with Down syndrome must
  always be examined
• If the baby has a translocation, then the
  parents chromosomes should be studied
• If one carries a balanced translocation other
  relatives should also be offered genetic
  counselling

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Objective

• This study was designed to evaluate the karyotype
  pattern, clinical features and other systemic
  anomalies of patients with Down syndrome at King
  Hussein Medical Centre.

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METHODS
Analysis of case files of Down syndrome patients
attending the Genetics Clinic was performed.
The following information was recorded

• Age
• Sex
• maternal age at childs birth
• craniofacial and other physical features
• presence and type of congenital heart disease
• gastrointestinal abnormalities
• hearing assessment
• ophthalmic evaluation

• complete blood count,
• kidney and liver function tests
• thyroid function tests
• cytogenetic evaluation.

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• Out of the 75 cases enrolled the results of
  chromosomal analysis were unavailable for 10
  patients.
• Echocardiography results were available for 72
  patients.
• Results of thyroid function tests were available
  for 60 patients.
• Hearing and ophthalmic evaluation evaluations
  were done for 55 patients.

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Results

• Age of children ranged from a month to 13 years.
• 45 were males and 30 were females.
• Male to female ratio (1.31).

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• Mean maternal age at birth of the affected child
  was 33.9 years 6.9 (range 18-48 years).
• Maternal age categories showed
• 8 mothers were less than 25 years
• 30 mothers were between 25 and 35 years
• 37 mothers were over 35 years of age

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Mother age and karyotype
Mother age category nondisjunction translocation mosacism Total ()
18-25 years 6 0 2 8(12.3)
25-35 years 25 2 0 27(41.5)
gt 35 years 29 0 1 30(46.2)
Total 60(92.3) 2(3.1) 3(4.6) 65(100)
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Karyotype frequencies in different countries
Source Auther Total No trisomy translocation mosaic nonclassic
Current study Amayreh et al 2009 65 60 (92.3) 2 (3.1) 3 (4.6) 0
Malaysia Azman et al 2007 149 141 (94.6) 1 (0.7) 7 (4.7) 0
Ireland Devlin 2004 208 197 (94.7) 3 (1.45) 8 (3.85) 0
Egypt Mokhtar et al 2003 673 642 (95.4) 18 (2.7) 5 (0.7) 8 (1.2)
England and wales Mutton et al 1996 5737 5411 (94.4) 220 (3.8) 66 (1.2) 40 (0.7)
England English et al 1989 65 63 (96.9) 1 (1.5) 1 (1.5) 0
Belgium Cassiman et al 1975 88 81 (92.1) 6 (6.8) 1 (1.1) 0
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Congenital heart disease
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Hearing impairment

• Impaired hearing in 30 (55) out of 55
• 18 had conductive hearing loss flat tympanic
  membrane and middle ear effusion
• 12 had absent OAE

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Visual defects

• Opthalmological abnormalities were found in 19
  (34.5) out of 55 cases
• refractive errors 5
• squint 4
• nystagmus 2
• Others pigmentary changes etc

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Gastrointestinal anomalies

• Gastrointestinal anomalies were found in 5 (7)
  cases out of 75 patients
• two had diaphragmatic hernias
• two haad gastoeosophegeal reflux
• one had duodenal atresia.

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Others

• Thyroid function, 16(27) out of 60 patients had
  hypothyroidism.
• Complete blood count showed mild anaemia in 5
  cases
• Alkaline phosphatase was high in 5 patients and 2
  had clinical rickets
• All of the screened patients had negative tTG.

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Conclusion

• Down syndrome (DS) is relatively a common
  disorder in paediatric practice
• The rise in average maternal age could bring with
  it an increase in the number of pregnancies
  affected by Down syndrome
• Nondisjunction consitutes more than 90 of cases
• 49 of cases were born to mother older than 35
  years
• Children with Down syndrome have multiple
  malformations and mental impairment, they have an
  increased risk of congenital heart disease,
  gastrointestinal anomalies, thyroid disease,
  hearing and visual disorders, obstructive sleep
  apnea, acquired hip dislocation and leukaemia
• Early diagnosis and a proper screening and follow
  up of these children is of great importance,and
  referral to specialised clinics is needed

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Thank you