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

1. 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

2. 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 baby�s facial appearance: difficult to acertain! Chromosomal analysis is needed to; confirm the diagnosis determine the risk of recurrence for genetic counselling

3. 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

9. 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 Alzheimer�s disease

11. 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

13. 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 21:21 translocation, all the offspring will have Down syndrome If neither parent carries a translocation, the risk of recurrence is <1%

14. 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

15. 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.

16. METHODS; 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.