Gastroenterology and Hepatology From Bed to Bench EDITORIAL

©2014 RIGLD, Research Institute for Gastroenterology and Liver Diseases

Gastrointestinal disorders in Down syndrome

Geoffrey Holmes
Royal Derby Hospital, Derby, UK

John Langdon Down, an English physician, first expectancy has risen dramatically through the years
described Down syndrome in 1866 but it was not and by the end of 2002 the median was 60 years (3,
until 1959 that Dr Jerome Lejeune from Paris 7). It is likely that this increase in survival will
showed an association with chromosome 21. Down continue. With proper management particularly in
syndrome is the most common chromosomal dedicated clinics (8) those with Down syndrome can
abnormality occurring in humans and is caused by go on to lead fulfilled, productive lives with some
the presence of all or part of a third copy of moving into higher education and employment. This
chromosome 21. Recent exciting research has shown brief review is concerned only with gastrointestinal
that trisomy silencing may offer new treatment associations.
possibilities (1). Down syndrome presents with Children and adults with Down syndrome will
typical physical features particularly of the face, and exhibit gastrointestinal symptoms from time to time
varying degrees of hypotonia and intellectual such as vomiting, diarrhoea, constipation, abdominal
disability (2). Most children are born to mothers pain and discomfort that resolve with minimal or no
under the age of 35 years but the incidence of Down intervention much as in others. However, they may
syndrome increases with maternal age. The develop structural and functional disorders of the
condition is encountered worldwide with an gastrointestinal tract and related structures more
incidence of 1 in 650-1000 live births (3). It is commonly. Estimates of how commonly these occur
associated with a number of conditions including have often been derived from selected populations
heart and spinal defects, endocrine disorders such as those attending special clinics for Down
particularly a high frequency of Hashimoto’s syndrome when about 10% of children and teenagers
thyroiditis and to a lesser extent Graves disease (4), will be affected (9). Over three quarters of neonates
and respiratory and eye problems. In recent years attending clinics may have gastrointestinal problems
with more enlightened attitudes to disability, the including feeding difficulties or developmental
development of surgical techniques to correct defects anomalies (10). However, using a registry of
and improved general care, the survival of infants congenital malformations covering an area of France
and life expectancy for Down syndrome have risen for the years 1979 to 1996 when 398 new cases of
dramatically. About sixty years ago in Birmingham, Down syndrome were identified, 6% were found to
England only 45% of infants survived the first year have intestinal atresias (11). Medical records for all
and only 40% were alive at 5 years (5). Fifty years live born children with Down syndrome born
later in a study also from England, 78% of infants between 1973 and 1980 in northern Sweden were
with Down syndrome and a congenital heart defect analysed and 7.3% were found to have
survived for 1 year and 96% of those without gastrointestinal malformations (12).
anomalies (6) . An Australian report showed that life

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 Holmes G 7

Structural problems may affect the hepatitis A and B can be high and indicates the need
gastrointestinal tract from the mouth to the anus but for immunisation (16).
many conditions will occur in Down syndrome with Coeliac disease (CD) that is associated with
similar frequency to other children. However, Down syndrome can present at any age. Symptoms
oesophageal, duodenal, and small bowel atresia or in children and adults are protean and include growth
stenosis, annular pancreas causing small bowel failure, malaise, vomiting, abdominal distension,
obstruction, imperforate anus and Hirschsprung diarrhoea and constipation. Unexplained anaemia,
disease may be more common than in the general iron and calcium deficiency, point to the diagnosis.
population (13). Screening studies have shown a prevalence of
Obstruction in the gastrointestinal tract may be CD in Down syndrome of about 5% and because of
detected before birth by imaging techniques and so this strong association some have advocated
allow for planned intervention early after birth. If screening all subjects using human tissue
diagnosis is not made pre-birth no bowel actions, transglutaminase (htTG) and/or endomysial
vomiting and a distressed baby indicating abdominal antibodies (EMA) antibodies (17). Screening should
pain will suggest bowel obstruction and the need for begin at the age of 3 years and be repeated every 2-3
urgent surgical intervention. Imperforate anus either years since a single negative test will not rule out CD
total or partial may also occur and require surgery. for life (18). By establishing the HLA status of
Hirschsprung disease affects about 2% of those with individuals and excluding those from the programme
Down syndrome and manifests as a distended who do not carry HLA-DQ2 or HLA-DQ8, markers
abdomen, poor weight gain, vomiting and that are necessary for CD to develop, the number of
constipation. Short segment disease can be difficult screening tests can be reduced by 60% (18, 19) .
to diagnose. Screening has the potential to diagnose all cases
Gastro-oesophageal reflux should be suspected in irrespective of symptoms. Whether this is an
a child who appears uncomfortable during or after effective approach is still not clear because those
feeding. Down children are prone to this because with minimal or no symptoms may not be persuaded
they spend less time in the sitting position and to undergo a small bowel biopsy to confirm the
muscle tone in the lower oesophageal sphincter may diagnosis or adhere to a gluten free diet.
be reduced thus allowing reflux. It is possible that A second approach to make the diagnosis of CD
developmental abnormalities in the enteric nervous in Down syndrome is a case-finding strategy that
system also have a role to play here and also perhaps targets only those with clinical features consistent
in other functional disturbances (14, 15). Too liquid with the diagnosis e.g. symptoms, unexplained
feeds may contribute to the problem. Aspiration anaemia, hypertransaminasemia, family history. If
pneumonia may be a presenting feature of reflux and the diagnosis is suspected, CD specific antibodies
early evaluation of oesophageal function should be should be looked for and if positive a small bowel
undertaken in children with chronic cough or biopsy advised to confirm the diagnosis. Antibody
recurrent pneumonia. Reflux can easily be negative CD occurs and may be due to a false
misdiagnosed as asthma and so remain untreated. negative test or IgA deficiency in which case IgG
Adults with Down syndrome are also prone to a based tests are available. If the diagnosis of CD is
wide range of gastrointestinal problems including strongly suspected a duodenal biopsy should be
reflux, obesity, constipation and diarrhoea. Infection advised even in the absence of antibodies.
with H.pylori appears to be more common but the Some patients with high levels of tTG (>10 times
implications are not clear (16). Non-immunity to the upper limit of normal) may not require biopsy to
establish the diagnosis of CD because this

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8 Gastrointestinal disorders in Down syndrome

accompanies diagnostic histology. This has already 10. Spahis JK, Wilson GN. Down syndrome: perinatal
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