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G186 XY GONADAL DYSGENESIS AND FRIEDREICH’S ATAXIA: A NEW GENE TO DISCOVER!
W. El-Matary1, D. E. Young1, P. D. Cameron1, A. M. Proctor2. 1Department of Paediatrics, Glan Clwyd Hospital, North Wales; 2Department of Clinical Genetics, University Hospital of Wales, Cardiff
Background: Friedreich’s ataxia is an autosomal recessive condition classified as a spinocerebellar degeneration. It is due to an abnormal sequence of the DNA triple nucleotide repeat on the long arm of chromosome 9. XY gonadal dysgenesis is a sporadic condition of failure of normal gonadal development. Various genetic causes have been identified; one is a defect on the short arm of chromosome 9. We describe a case of two rare genetic conditions presenting in the same patient.
Case: A 10 year old girl presented with ataxia. Investigations revealed normal blood immunoglobulins, creatinine kinase, liver function tests, calcium, magnesium, copper, ceruloplasmin, and alpha foetoprotein. A magnetic resonance imaging scan demonstrated no intra-cranial abnormality. Genetic analysis revealed a diagnosis of Friedreich’s ataxia. DNA testing confirmed the genetic defect of homozygous GAA hyperexpansion and positivity of the Friedereich’s ataxia gene on chromosome 9. At the age of 16, she did not develop any pubertal features. Further investigations revealed normal thyroid function, elevated LH at 62.4 mIU/L and FSH at 146 mI/L, with oestradiol at 51 pmol/L. These results were consistent with primary ovarian failure. Cytogenetic analysis showed a karyotype of 46 XY. Fluorescent in situ hybridisation studies using the SRY probe showed the presence of the SRY gene on the Y chromosome confirming the diagnosis of XY gonadal dysgenesis.
Conclusion: The Friedreich’s ataxia gene, known as FRDA, has been localised to the proximal long arm of chromosome 9. XY gonadal dysgenesis may be caused by a deletion of a locus situated on the distal short arm of chromosome 9. The combination of these two genetic diseases is obviously extremely unusual and we hypothesise the presence of a new sex determining gene adjacent to FRDA.
G187 SUBMUCOUS CLEFT PALATE: NEW PERSPECTIVES ON OLD THEMES?
A. Habel1, N. El Hady2, B. Sommerlad1,3. 1Great Ormond Street Hospital for Children WC1N 3JH; 2West Middlesex University Hospital; 3Broomfield Hospital
Introduction: Velopharyngeal insufficiency (VPI) symptoms include feeding difficulties and nasal regurgitation from early infancy, hypernasal speech, and chronic middle ear disease. Submucous cleft palate (SMCP) and occult SMCP are common causes of VPI in childhood.
Aims: To identify characteristics in the presentation of (SMCP) and relate them to pointers for improved awareness in clinical practice.
Methods: Retrospective casenote audit and parental questionnaire of referrals from 1987 to 2002 to a two site DGH/tertiary specialist centre.
Results: SMCP and occult SMCP were detected in 154 patients and 117 (76%) casenotes were informative. Of these, 70% had SMCP, 18% occult SMCP, and 12% bifid uvula with SMCP. Ages ranged from 1 day to 15 years at diagnosis and averaged 1.2 years (median 3.5 years) compared with 10.8 years reported 25 years ago. Associated malformations occurred in half the cases, 22q11 the commonest at 42 (36%) of the total. 17 (40%) of the 42 were detected at post-operative follow up. Feeding difficulties and nasal regurgitation were present at all ages. Speech difficulties were common (94%) in 2+ year olds. Middle ear symptoms were present in 57%. Across the age groups 86% had symptoms before detection and diagnosis. Those with malformations frequently attended hospital for other problems (60%), non-syndromic individuals (13%) less so. Post-adenoidectomy presentation, in only four children, was low, possibly reflecting ENT services were more aware than before of VPI as a complication.
Conclusions: Feeding, speech, and middle ear symptoms are useful indicators of VPI especially in the presence of other congenital abnormalities. The finding of SMCP should alert the clinician to the possibility of an associated syndrome, in particular 22q11 deletion. Previously seen cases of SMCP/VPI should be reviewed and tested for the 22q11 deletion when clinically indicated.
G188 A CHROMOSOME 2 INTERSTITIAL DELETION (2q14.2q21.1) IN A 4 YEAR OLD WITH IMMOTILE CILIA SYNDROME
A. IqbaL, V. Rao, N. Shannon. Child Health Department, Walsall PCT, Clinical Genetics, Birmingham Women’s Health Care Trust
We present a case of a male child (HN) with a chromosome 2 interstitial deletion and immotile cilia syndrome. He was born as a result of IVF and presented at the age of 2 weeks with failure to thrive. He had a prominent metopic ridge on his forehead, small anterior fontanelle, and narrow palpebral fissures. Chromosome analysis showed an interstitial deletion of the long arm of chromosome 2 (46,XY,del(2)(q14.2q21.1)). This rare chromosome abnormality has been reported in association with Peter’s anomaly, agenesis of corpus callosum, and cerebral atrophy. Cardiac and renal anomalies have also been reported. HN has had a normal brain CT, echocardiogram, and ophthalmic and renal investigations. He is growing and developing normally. However, he has been prone to frequent coughs and colds and has had hospital admissions for severe chest infections. Genetic testing showed the same chromosome deletion in the father, paternal aunt, and grandfather.
The father was diagnosed as having immotile cilia syndrome in childhood, thus explaining his infertility. The parents are first cousins with multiple consanguinity in the family. With this in mind, and the history of chest infections, HN was investigated, and was found to have immotile cilia on nasal mucous membrane biopsy. Interstitial deletion of chromosome 2 (2q14q21) is a rare abnormality. Only two other cases have been reported with these breakpoints. In both the deletion was de novo and, in contrast to our case, was associated with significant congenital abnormalites and developmental delay. In the light of the unusual presentation in our case comparitive genomic hybridisation was used to confirm the deletion and exclude a cryptic chromosome rearrangement. Immotile cilia syndrome is an autosomal recessive condition caused by abnormal ciliary ultra structure and function. Although it is genetically heterogeneous there are no known loci on chromosome 2. It is likely that the two conditions are occurring independently as the paternal grandfather has the chromosome deletion with no evidence of immotile cilia. This case shows the importance of considering autosomal recessive diagnoses in the wider family where multiple consanguinity is present.
G190 DO INFANTS WITH MINOR EAR MALFORMATIONS NEED ROUTINE RENAL ULTRASONOGRAPHY?
S. A. Deshpande, H. Watson. Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ
Background: There are conflicting reports about the frequency of urinary tract abnormalities among infants with minor ear malformations.1,2 We wished to determine if infants with isolated minor abnormalities of the external ears (pre-auricular skin tags and sinuses, and ear pits) are at an increased risk of renal malformations.
Methods: Consecutive infants with isolated minor ear malformations were offered renal ultrasonography by qualified, experienced ultrasonographers over a 41 month period.
Results: Ninety one among 12 254 liveborn infants (7.4/1000) were noted to have isolated minor ear abnormalities on routine neonatal examination. Preauricular skin tags were the commonest abnormality (78), followed by misshapen pinnae (7), preauricular sinuses (3), and pits (3). Eighty one (89%) infants underwent renal ultrasonography at a median (interquartile range) age of 37 (29–48) days. Only 1 (1.2%) infant had mild unilateral pyelectasia (renal pelvic diameter of 9 mm) but no evidence of vesico-ureteric reflux on cystography. This was similar to the frequency of renal abnormalities (including pyelectasia) detected on routine antenatal scans among 5625 births in Shropshire (1.3%, p 1.0.)
Conclusion: Renal ultrasonography is not indicated routinely for newborn infants with isolated minor ear malformations.
G191 USE OF COMPLEMENTARY OR ALTERNATIVE MEDICINE IN CHILDREN WITH, AND WITHOUT, CHRONIC DISORDERS
L. McCann, S. Newell. Leeds General Infirmary in association with MMedSc Child Health, University of Leeds
Aims: To evaluate whether children with chronic illness are more likely to use complementary or alternative medicine (CAM) compared with a healthy population.
Methods: A questionnaire based descriptive study using a structured interview technique for groups of 25 children with cerebral palsy, inflammatory bowel disease, and cancer, compared with a group of 25 healthy children.
Results: Children with chronic disease are more likely to use CAM than healthy children (40% prevalence (95% CI 34.5 to 45.5) as compared with 12% prevalence (95% CI 1 to 23, p 0.009)). Children with cerebral palsy are significantly more likely to use CAM than healthy children (56% in the cerebral palsy group compared with 12% in the healthy group, p 0.001). Children with inflammatory bowel disease are significantly more likely to use CAM than healthy children (28% in the inflammatory bowel disease group compared with 4% in the healthy group, p 0.02). CAM use is positively associated with an older age group of children. There is no significant difference between sex and religious beliefs between CAM users and non-CAM users. However, children are significantly more likely to use CAM when also used by family members (62% compared to 32%, p 0.039). Fifty five per cent of families do not inform their doctors about use of CAM in their children. Families would like to see a greater use of CAM within a hospital setting.
Conclusions: Paediatricians should be aware of possible CAM use in their patients, particularly in those with chronic disease. Families should be questioned as to their use of CAM within a paediatric history, as it may have important implications for possible adverse effects and interactions with orthodox medicine.
G192 BLACKBURN ASIANS WITH A FAMILY HISTORY OF RECESSIVE DISORDERS NEED INTENSIVE COUNSELLING REGARDING THE RISKS ASSOCIATED WITH COUSIN MARRIAGE
J. Benson, S. Korwariwalla. Queens Park Hospital
Background: Recessive disorders cause considerable morbidity in the Blackburn Asian community. Approximately 60% of local Asian marriages are consanguineous. Paediatricians have been unsure how best to tackle the problem.
Methods: (1) A database of recessive disorders was established from lists provided by local consultants, regional specialists, and death registers; (2) a questionnaire assessed local health professionals’ opinion on the barriers to uptake of genetic advice; and (3) 45 Asians parents and 14 family members were interviewed at home to ascertain their understanding of recessive disorders.
Results: (1) 272 children under 16 years with a recessive disorder were identified in the Blackburn health district. 207 were Asian. 55 Asian children and 11 white died. Recessive disorders are 12 times as prevalent in the Asian population compared with the white, and occurred in 13/1000 Asian births. 83 different disorders were identified. There has been no reduction in recessive disorders over the past 16 years. (2) Health professionals thought the main barriers to acceptance of genetic services were religious and cultural beliefs and language. Paediatricians were much more used to giving genetic advice than health visitors, GPs, or obstetricians. (3) Most parents had received genetic counselling. However, extended family members had no understanding of genetic disease, were not aware of their increases risk of recessive disorders if they married cousins, and none had received genetic counselling. The most common reason given by parents for not taking up genetic advice was religious objection to termination. There were considerable cultural and language barriers to providing an acceptable genetic service to these families of an index case.
G193 FATTY LIVER DISEASE IN CHILDREN IN THE WEST MIDLANDS
H. M. Evans1, U. Baumann1, P. J. McKiernan1, J. M. W. Kirk2, M. G. Shaikh2, D. A. Kelly1. 1The Liver Unit and 2Department of Endocrinology, Birmingham Children’s Hospital
Background: The incidence of non-alcoholic fatty liver disease is increasing worldwide in adults and children and may be related to the global epidemic of obesity. The more severe form, non-alcoholic steatohepatitis (NASH), can progress to end stage liver disease in adults, but little is known about outcome in children.
Aim: To describe the demographic, biochemical, and histological features of children with fatty liver referred to a national liver unit.
Methods: All children (n 38; 21 male; median age 13.1 years) referred with fatty liver between Jan 2000 and Oct 2003 underwent investigation to exclude other liver diseases and to identify insulin resistance using the homeostasis model assessment (HOMA) method and C-peptide. All had abdominal ultrasonography (USS) and also liver biopsy if raised ALT (>1.5 times normal) after 6 months of diet and increased exercise.
Results: Median body mass index z score was +3.0 (−3.9 to +4.5) with 30/38 being obese (BMI z score >2.0). 1 had type 2 diabetes, 17 had insulin resistance by HOMA, and 11 had raised C-peptide suggesting insulin overproduction. 24 had raised triglycerides, 11 had autoantibodies, and 17 had low T4 and/or raised TSH. 36 had a USS suggesting fatty liver. 27/30 who underwent liver biopsy had fatty liver, (including two with normal USS). Of these, 10 had NASH and three had cirrhosis. Two biopsies were normal (despite abnormal USS) and one had glycogen storage disorder. There was no correlation between the severity of fatty liver on biopsy and ALT, insulin resistance, or triglycerides.
Conclusions: Fatty liver disease is a major health concern in British children. Most are obese and insulin resistance is common. USS is a non-invasive method of evaluation but is not sensitive nor specific and liver biopsy is the only method to diagnose NASH. Further evaluation of the role of autoantibodies and thyroid dysfunction is required.
G194 CHILDHOOD OBESITY—THE EXTENT OF PROBLEM IN A DEPRIVED AREA OF WALES
A. Gandhi, R. J. H. Morgan, M. Balman. Royal Glamorgan Hospital, Llantrisant CF72 8XR
Aims: 1) To estimate the prevalence of overweight and obese children of the deprived valleys of Rhondda, Cynon, and Taff Ely; 2) to assess usefulness of waist centile estimation in children; and 3) to identify target groups for possible interventions.
Methods: A prospective observational study involving the calculation of body mass index (BMI) for all children above the age of 6 months, attending the paediatric outpatients of Royal Glamorgan Hospital over a period of 4 months. In children 3 years and older waist measurements were also performed and centiles calculated. Two trained paediatric nurses using standardised equipment carried out all measurements.
Results: Data were collected from October 2002 to January 2003 (inclusive). Of the 1184 children attending the outpatients 992 satisfied the study criteria. Using the BMI centiles 13.3% of the children were obese and another 13.4% were overweight. The number of obese and overweight girls exceeded boys. The prevalence of obesity was lowest in children younger than 3 years and increased with age. In children 3 years and older BMI measurements and waist centile measurements were comparable.
Conclusions: Childhood obesity is a major public health problem in our area. Routine use of BMI centile charts as a part of paediatric assessment should help in its identification. Children below 3 years need to be recognised as target group for prevention of obesity. Waist circumference measurements add little and may be associated with technical difficulties.
G195 HELICOBACTER PYLORI INFECTION AND RECURRENT ABDOMINAL PAIN IN CHILDREN: DO WE NEED TO DEFINE SITE OF PAIN MORE PRECISELY?
D. Ashok, P. Phyu, B. I. McLain. Department of Paediatric Gastroenterology, University Hospital of North Tees, Stockton
Aims: The role of H pylori as a cause of recurrent abdominal pain (RAP) in children is widely debated. The purpose of the present study was to analyse the association of H pylori infection and RAP and compare infection rates in children with recurrent periumbilical pain and recurrent epigastric pain.
Methods: This is a prospective study on a cohort of 100 children aged 3 to 15 years, who presented to a tertiary gastroenterology centre and met the standard criteria for RAP. Baseline investigations and a validated H pylori antibody assay (IgG-ELISA) were performed on all children with RAP. Upper GI endoscopy and rapid urease test (CLO test) on biopsy specimens were performed depending on the severity and chronicity of symptoms.
Results: In 24 children (24%), a definitive diagnosis of H pylori infection was made on the basis of endoscopy findings (antral nodularity and gastritis) and rapid urease testing. Three of these children also had duodenal ulcers. In 37 children with predominantly epigastric pain, 21 tested positive (positive predictive value 57%). The likelihood ratio of having H pylori infection with epigastric pain was 4.6. In 73 children with poorly localised or periumbilical pain, only 3 (4%) tested positive. The negative predictive value for H pylori infection in children without epigastric pain was 95%.
Conclusions: This study clearly identifies a subset of individuals within a wider group of recurrent abdominal pain, who appear to have a different aetiology to their pain. Epigastric pain +/− tenderness in the epigastrium accounted for 37% of this group, yet contained 21/24 of the H pylori positive patients. No other symptoms (or group of symptoms) were as predictive of H pylori status. Recurrent epigastric abdominal pain is associated with H pylori infection but recurrent periumbilical pain is not. Further detailed studies are required to identify clearance of infection and long term symptomatic improvement in this group.
G196 YOUNG PERSONS’ DIABETES CLINIC: A PARENT/PATIENT PERSPECTIVE
A. Richardson1, P. C. Paul2, W. Sultan2, S. Kerr2, U. Das2, M. Didi2. 1University of Liverpool UK; 2Royal Liverpool Children’s Hospital, Alder Hey
Introduction: Transfer to adult care is a major life event for young people with chronic illness, and the appropriate management of this transition is an essential part of best practice. National Service Framework aims at smooth transition of care from paediatric diabetes services to adult services, either directly or through a young person’s clinic.
Aim: To evaluate the felt need for an adolescent diabetes clinic and to determine the view points of young people and parents regarding the age group, location, and structure of these clinics.
Method: A prospective questionnaire survey was conducted for all parents and children aged 10 and above, who attended the diabetes clinics. One parent per child participated in the survey. Specially designed separate user friendly questionnaires were used for parents and children. This was accompanied by a covering letter explaining the purpose of the study.
Results: Ninety nine out of 116 (85%) questionnaires were returned. Forty one were from children, including 21 females. Overall 92.9% of the participants (n 92) felt the need for a separate adolescent clinic. The majority, 78%, in each group thought that the clinic should be offered for patients aged 12 to 18 years. However, 15.3% of the participants, including eight children, opted for under 16 clinics. Fifty per cent of the parents wanted the clinic to be held in a paediatric unit. Seventy per cent of the teenagers preferred the clinics alternating between an adult centre. Eighty nine per cent (n 35) of the children preferred day time clinics, compared with 77% (n 40) of the parents (χ2, p 0.04).
Conclusions: The majority of young people and their parents preferred a young person’s diabetes clinic for 12–18 year olds. Older children preferred shared care with the adult service with clinics held alternating between the adult and paediatric centre.
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