More Medical Issues in Down's Syndrome. A conference held under the auspices of the Royal Society of Medicine GI DISORDERS Forum on Learning Disability and The Down's Syndrome Medical Interest Group. Royal Society of Medicine, London, Thursday 26th April 2001 Chaired by Dr Patricia Jackson, Edinburgh and Dr Liz Marder, Nottingham Gastrointestinal disorders in people with Down's syndrome: an overview Summary of a presentation by Dr Charlie Charlton Consultant Paediatric Gastroenterologist, University Hospital, Queen's Medical Centre, Nottingham, UK There is an increased incidence of gastrointestinal until proved otherwise. Other presenting symptoms are problems among people with Down's syndrome. It is regurgitation, diarrhoea and/or abdominal pain. These therefore important to be aware of the conditions children usually do extremely well following surgery. involved, and of their presenting symptoms and manage- ment. Hirschprung's disease Gastrointestinal conditions associated with Down's Hirschprung's disease is due to failure of migration syndrome can be roughly grouped into three problem of the ganglion cells to the submucosal and myenteric areas (Panel 1). plexuses of the large bowel. The affected segment can vary in length from very short to much longer. It is important to remember that the affected area has a risk Panel 1: Gastrointestinal conditions associated of stasis, infection, enterocolitis and perforation. This with Down's syndrome is one reason why early diagnosis is important. · Embryological and structural Essential surveillance for all newborns with Down's ­ Anorectal (imperforate or stenosis) syndrome should therefore include: ­ Duodenal or jejunal (atresia or stenosis) · An examination for imperforate anus in the delivery ­ Hirschprung's disease room in order to ensure that this has been excluded. · Motility and co-ordination ­ Feeding difficulties · Active observation of when meconium is first passed. ­ Constipation · Consideration of Hirschprung's disease following late ­ Toddler diarrhoea passage (more than 24 hours) of meconium in a child ­ Gastro-oesophageal reflux (GOR) with Down's syndrome. ­ Gall stones Although Hirschprung's disease is usually consid- · Autoimmune ered to present very early, around 50% of those with ­ Coeliac disease ­ Hepatitis Down's syndrome will present after one month of age. Presenting features include constipation in the first few months or constipation with failure to thrive in Embryological and structural problems the first year. There is an incidence of about 10% of anorectal and Diagnosis involves suction rectal biopsy which duodenal atresia or stenosis and around 2% incidence can be carried out on the ward. However, this has to of Hirschprung's disease in children with Down's syn- be done in conjunction with the laboratory as they will drome. These figures are much higher than for other need to prearrange some tests. If the diagnosis is con- children. It is therefore very important to be active about firmed, management usually consists of a defunctioning diagnosis so that these conditions are recognised early colostomy to remove the cause of obstruction followed and thereby better treatment can be achieved. by resection of the abnormal aganglionic segment and pull through of the normal bowel to the anus. It is Duodenal and jejunal atresias and stenoses important to remember that even after surgery, children The duodenal and jejunal atresias and stenoses tend to with Hirschprung's disease have a risk of enterocolitis present with bile-stained vomiting indicating obstruction which may be signalled by blood in the stools. © Down's Syndrome Medical Interest Group · Children's Centre · City Hospital Campus · Nottingham NG5 1PB · www.dsmig.org.uk T: 0115 962 7658 ext 45667 · F: 0115 962 7915 · info@dsmig.org.uk The outcome in Hirschprung's disease is problematic · Childhood Soiling: a guide for parents ­ which even in children who do not have Down's syndrome. includes a particularly useful section concerning the Complications include the necessity for stomas where child who will only go to the toilet with their nappy pull through has not worked, an ongoing risk of entero- on. colitis and difficulties with toilet training. The · Helping children with constipation ­ a very good prognosis for continence in those with Down's publication with straightforward language and word- syndrome is poor. ing. One in a series of Treatment Notes, produced by the Consumers' Association for patients based on matching information from the Drug and Hirschprung's disease Therapeutics Bulletin. · Around 2% incidence in children with Down's For further information on these publications, see syndrome Further reading. · 50% present after age 1 month · Early diagnosis is important Toddler diarrhoea · Careful early neonatal surveillance is required Toddler diarrhoea is a common problem which presents · There is a risk of enterocolitis both before and with a thriving child with undigested vegetable matter. after surgery · Surgical outcome is variable It can be quite difficult to exclude constipation in this · Prognosis for continence is poor group hence a good history and an abdominal examina- tion are necessary. Wherever possible, dieticians should be involved in Motility and co-ordination problems management of these children. Excessive intake of fruit Constipation juice is often causative and may be a particular problem Constipation can be a major problem for people with in Down's syndrome as fruit juice may have been given Down's syndrome and appears to be very common in in an attempt to overcome constipation. If decreasing children. Mobility may be an issue here as mothers the intake of fruit juice fails, lowering the amount of often say that when the baby started to move around roughage in the diet may be helpful. Alternatively, the constipation problem eased. It is always worthwhile Calogen® (long chain triglyceride dietary supplement, excluding hypothyroidism before moving on to treat- SHS International Ltd, Liverpool, UK) has been demon- ment regimens. strated to reduce the amount of stooling in a significant Many children are prescribed lactulose for constipa- number of children. Calogen® is available from hospital tion, usually 5 ml twice a day. One problem is that par- supplies and is quite palatable. ents are not given an endpoint ­ such as a soft daily stool A key factor as far as parents are concerned is to be ­ to work towards or advice about increasing medicines reassured that there is no underlying medical problem. stepwise until that endpoint is achieved. An information That may be sufficient to avoid any intervention but as chart about target stool consistency has been developed toilet training is often affected, a small amount of inter- by Dr KW Heaton in Bristol, UK for people with irritable vention may be enough to help relieve the problem. bowel syndrome and this is also very useful for those with constipation. The chart is illustrated and provided Toddler diarrhoea free by MovicolTM (iso-osmotic laxative, Norgine, · Exclude constipation Harefield, UK) representatives. Healthcare professionals · Reassure parents should aim towards providing information of this sort, · Involve dietician including leaflets, for parents. Two very useful publica- · Reduce or exclude fruit juices tions are: · Reduce roughage in diet · Calogen® may help Constipation Gastro-oesophageal reflux (GOR) · Worse before self-mobile Children with GOR exhibit milk vomiting, even though · Exclude hypothyroidism they are often well and thriving. However they should · Clear endpoints (e.g. soft daily stool) necessary be watched carefully for signs of complications and the for treatment regimens development of gastro-oesophageal reflux disease · Stepwise increase of laxative may be needed to achieve target endpoint (GORD) (blood in the vomit and failure to thrive). · Parent information leaflets are useful Although it is not a major contributory cause, the mental state of the mother it is always worth consider- ing as GOR often occurs when a mother is depressed. It In the general population, the peak incidence of is possible that the mother's mental state leads her to coeliac disease has been taken to be around eight over-interpret the symptoms. It is also important to take years old, followed by a drop off at around age 10 a very careful history as some parents who complain and another increase in incidence in early adulthood. about reflux and vomiting are not experiencing the However, as there currently appear to be more people amount of vomiting that others accept as being com- in the general population who present with the disorder pletely normal. later in life, the early adult peak is not so apparent. Also, If the child is well and there is no evidence of increasing numbers are being diagnosed with GORD, the aim should be to avoid intervention as this is lesser gastrointestinal and other symptoms but without often the most reassuring course of action for parents. If florid signs of the disorder. Symptoms and general well- the problem is socially unacceptable, thickeners such as being are regularly improved by a gluten-free diet. Carobel Instant (Cow & Gate, Nutricia, Trowbridge, In the UK, there is probably around a 1­2% risk of UK) and Enfamil AR® (Mead Johnson Nutritionals, coeliac disease in Down's syndrome and the figures Bristol Myers Squibb, Hounslow, UK) may be useful. are higher in some other countries. In individuals with As Enfamil AR® has a thin consistency in the bottle but Down's syndrome, as in the general population, the a thicker consistency in the stomach, it is particularly condition is lifelong if diagnosed after 2 years of age. useful in bottle-fed infants. Under 2 years of age, a transient enteropathy can mimic If there are signs and symptoms of acute GORD, fur- the disorder. ther investigation is needed and the condition should not be treated pragmatically. Screening for coeliac disease Panel 2 lists serum markers currently used when screen- ing for coeliac disease. It is important to remember that Gastro-oesophageal reflux (GOR) these are only screening tests and to make a diagnosis there should be increasing changes in the small intestine · If there is no evidence of GORD, try to avoid intervention and a response to a gluten-free diet. Furthermore, if tests · Consider mother's mental state are negative but symptoms are present, a biopsy should · Milk thickeners may help always be considered. · If GORD is suspected, further investigation is essential Panel 2: Markers for coeliac disease Gliadin antibodies ­ IgG and IgA. Many children Gall stones and abdominal pain have a late switch on of IgA; therefore in children Gall stones are an uncommon, but increasing, finding in below age ten, the IgG gliadin antibody must be children with Down's syndrome and tend to be discov- checked. ered by chance during radiological examination. Current Endomysial antibodies (EMA) ­ the most sensi- advice is that if they are asymptomatic surgery is not tive and specific test, with 95% of those with coeliac disease testing positive. Screening of indicated. symptomatic populations picks up only about 5% who do not have coeliac disease. Autoimmune problems Tissue transglutaminase antibody ­ a relatively Coeliac disease new test which is ELISA-based and less expen- Coeliac disease can present with diarrhoea, failure to sive than EMA. This will almost certainly replace thrive, general misery, abdominal distension and iron EMA in the next few years. deficiency anaemia. Given this symptomatology, it is always advisable to exclude giardiasis. Although antibody screening tests have undoubtedly identified children whose general well-being can be Coeliac disease improved once the condition is recognised, whole popu- · Universal screening not recommended lation screening of individuals with Down's syndrome · Yearly clinical review of features that suggest for coeliac disease is probably not warranted. A more coeliac disease (Panel 3) useful approach is to make careful enquiry on a regular · Exclude giardiasis · Lifelong condition if diagnosed after age 2 years basis regarding symptoms and signs and to screen only · Treat with gluten-free diet as for all children those with possible symptoms. It is important to remem- ber that symptoms may be relatively mild and not neces- DSMIG is indebted to the Down's Syndrome Association who have met all the production costs for this summary. sarily brought to the attention of the doctor, and there- Autoimmune hepatitis is a rare but recognised disorder fore specific enquiry is always needed. Panel 3 lists which probably occurs more frequently among those symptoms and signs which may merit coeliac screening. with Down's syndrome. It may present with jaundice, but as this can also indicate hypothyroidism and gall stones these conditions must be excluded from diagnosis. Panel 3: Symptoms and signs which merit Autoimmune hepatitis may present with general malaise screening for coeliac disease and aches or a more definite arthropathy. Liver enzymes · Failure to thrive may not be dramatically elevated even in the presence of · Chronic anaemia quite active hepatitis. Chronic ongoing hepatitis can also · Existing thyroid disease or diabetes · Diarrhoea or other GI disturbance be due to hepatitis B infection, which is also over-repre- · Abdominal distension sented in those with Down's syndrome. · General misery/lethargy Summary Diagnosis The following gastrointestinal disorders occur more Diagnosis involves identifying positive markers such frequently in those with Down's syndrome: as increasing changes in the small intestine (Figure 1) · Structural/embryological conditions, such as atresias and a response to a gluten-free diet. Under two years and Hirschprung's disease of age, transient enteropathy is a possibility and there- · Motility and co-ordination disorders such as fore these children need to be rechallenged and a biopsy constipation, gastro-oesophageal reflux and taken around age five to confirm the diagnosis of coeli- feeding problems ac disease. · Autoimmune conditions, including coeliac disease and autoimmune hepatitis. Autoimmune hepatitis It is important to be active about diagnosing these conditions in order that they are recognised early and a) thereby better management can be achieved. Further reading Consumers' Association. Helping children with constipation http://omni.ac.uk/whatsnew/detail/1101236.html Dobson P. Childhood Soiling: A Guide for Parents. 1998 The Enuresis Resource & Information Centre (ERIC). http://www.enuresis.org.uk/shop.html Heaton K. The Bristol stool form scale. In: b) Understanding your Bowels. 1999 Family Doctor Publications in association with the British Medical Association. ISBN 1-898205-08-6. Marder, EM. Gastrointestinal problems in children with Down's syndrome. Down's Syndrome Association newsletter 1996. http://www.dsmig.org.uk/library/ articles/gastro-article-marder.pdf Pueschel SM. Gastrointestinal concerns and nutritional issues in persons with Down's syndrome. Down Syndrome Quarterly 1999:4 (no 4):1­11. Figure 1: Biopsies from a) healthy patient demonstrat- Quinn FM, Surana R, Puri P. The influence of trisomy ing large villous height-to-crypt depth and a normal 21 on outcome in children with Hirschsprung's disease. number of intraepithelial lymphocytes, and b) a patient with coeliac disease, showing total villous atrophy with J Pediatr Surg 1994; 29(6):781­3. a completely flat surface, very fine crypts and a very heavy infiltrate. Comparing the two biopsies, b) is A complete transcript of this presentation, together with dense with inflammatory cells. Figure reproduced from references, is available at www.dsmig.org.uk. Fast Facts ­ Coeliac Disease (2000), by G Holmes and C Catassi, with the permission of Health Press Ltd, Oxford. © 2002 Down's Syndrome Medical Interest Group. Produced by Oxford PharmaGenesisTM Ltd, UK