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A Survey of Phenotypic Features in Juvenile Polyposis J Med Genet: First Published As 10.1136/Jmg.35.6.476 on 1 June 1998

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A Survey of Phenotypic Features in Juvenile Polyposis J Med Genet: First Published As 10.1136/Jmg.35.6.476 on 1 June 1998 47646Med Genet 1998;35:476-481 A survey of phenotypic features in juvenile polyposis J Med Genet: first published as 10.1136/jmg.35.6.476 on 1 June 1998. Downloaded from Devendra C Desai, Vicky Murday, Robin K S Phillips, Kay F Neale, Peter Milla, Shirley V Hodgson Abstract potential. 1-8 Extracolonic features have been Solitary juvenile polyps are quite frequent reported in association with JP, but the exact in children, but juvenile polyposis (JP) is a proportion of affected subjects with such rare autosomal dominant trait character- abnormalities has not been ascertained.' 911 ised by the occurrence of numerous Juvenile polyps may occur as a feature of a polyps in the gastrointestinal tract. Extra- number of genetic syndromes, including colonic phenotypic abnormalities are well Bannayan-Riley-Ruvalcaba syndrome (charac- documented in patients with familial terised by macrocephaly, mental retardation, adenomatous polyposis and Peutz-Jeghers and pigmented spotting of genitalia6 12 14), syndrome and can allow a clinical diagno- Cowden syndrome (a multiple hamartoma sis to be made before the bowel pathology syndrome characterised by hamartomas of becomes available. Though described, multiple organs, macrocephaly, trichilemmo- characteristic extracolonic abnormalities mas, and thyroid and breast disease, leading to have not been clearly defined in juvenile a high cancer risk in these organs'9), and Gor- polyposis. We sought to determine lin syndrome (an autosomal dominant condi- whether there are consistent extracolonic tion characterised by multiple naevoid basal phenotypic abnormalities in JP patients carcinomas, odontogenic keratocysts, skeletal and how frequently this would allow diag- abnormalities such as macrocephaly, hyperte- nosis of one of the genetic syndromes lorism, rib and vertebral anomalies, short known to be associated with juvenile poly- metacarpals, pits in the skin of the palms and posis. soles, and intracranial calcification'2 16). Twenty-two JP patients underwent clini- The aim of this study was to determine the cal examination and data from one patient prevalence of extracolonic abnormalities in JP, Polyposis Registry, St were obtained from case notes. Those and to determine the possible contribution of Mark's Hospital, consenting to further investigations had x genetic syndromes to the aetiology of this con- Northwick Park, rays of the skull, chest, and hands and an dition. Molecular tests for germline mutations http://jmg.bmj.com/ Watford Road, Harrow, echocardiogram if clinically indicated. in the genes underlying the conditions diag- Middlesex HAl 3UJ, nosed in our patients are becoming available, UK Significant extracolonic phenotypic ab- D C Desai normalities were present in 18 patients (14 and we have some preliminary data about this, K F Neale male and four female), and included but further studies are required. R K S Phillips dermatological (13), skeletal (16), neurological (5), cardiopulmonary (4), The Hospital for Sick Materials and methods Children, Great gastrointestinal (3), genitourinary (4), and DIAGNOSTIC CRITERIA on September 29, 2021 by guest. Protected copyright. Ormond Street, ocular (1) features. In five patients the We took as our criteria for the diagnosis of London WClN 3JH, diagnosis of a genetic syndrome was juvenile polyposis any one of the following: (1) UK possible: two had Bannayan-Riley- P Milla three or more colonic juvenile polyps; (2) juve- J Ruvalcaba syndrome, two had Gorlin syn- nile polyps throughout the gastrointestinal and one had South Thames drome, hereditary tract; (3) any number of juvenile polyps in a Regional Genetics haemorrhagic telangiectasia (HHT, also patient with a family history of juvenile Centre (West), St known as Osler-Rendu-Weber syndrome). polyposis. 17 George's Hospital, Other patients had some features of these Blackshaw Road, conditions and of Cowden and Simpson- London SW17 OQT, UK Golabi-Behmel syndromes, but these PATIENTS V Murday Patients were ascertained through the St were not sufficient to allow a definitive Mark's Hospital Polyposis Registry, The Hos- Division of Medical diagnosis. Genet pital for Sick Children, Great Ormond Street, and Molecular (J7Med 1998;35:476-481) and Guy's Hospital, London, and via a Genetics, United Medical and Dental Keywords: juvenile polyposis; Cowden syndrome; Gor- questionnaire circulated to geneticists and Schools, 8th floor, lin syndrome; Bannayan-Riley-Ruvalcaba syndrome pathologists, and in a mailing to the members Guy's Tower, Guy's ofthe British Society of Gastroenterology. Only Hospital, London two patients (Nos 4 and 5), identified at St SE1 9RT, UK Juvenile polyposis JP) is an uncommon Mark's Hospital, had already been given a pro- S V Hodgson autosomal dominant condition characterised visional diagnosis of one of the syndromes dis- in Correspondence to: by hamartomatous polyps, usually the colon cussed. Dr Hodgson. but sometimes in the stomach and small A questionnaire was completed for each bowel.' These polyps have an abundant lamina affected subject, providing details including Received 28 August 1997 propria lacking smooth muscle (differentiating symptoms, investigations carried out, and treat- Revised version accepted for publication them from Peutz-Jegher polyps, which do con- ment received. An approach to the doctors con- 16 December 1997 tain smooth muscle) and have malignant cerned was made whenever it was necessary to A survey ofphenotypic features in juvenile polyposis 477 ing the jaw), and hands. Patients in whom clinical examination was suggestive of a cardiac abnormality underwent an echocardiogram. J Med Genet: first published as 10.1136/jmg.35.6.476 on 1 June 1998. Downloaded from Blood was obtained from some cases with informed consent for testing for germline mutations in candidate genes. Results Twenty-two patients were seen clinically and in one patient data were obtained only from case notes. Thus a total of 23 patients were included, x rays being performed in 14. Seven- teen were male and six female, with a median age of 29 years (age range 4-65 years). Patients 7 and 8 were brothers, patients 9 and 10 were from the same family, and patients 12 and 16 were mother and daughter. All other cases were sporadic. Extracolonic phenotypic abnormalities (table 1) were detected in 18 of the 23 patients (78%). Dermatological abnor- malities (including telangiectases and large numbers of pigmented naevi) were common (13 patients), as were skeletal abnormalities (16 patients). Other abnormalities included neurological (five patients and one patient with epilepsy), gastrointestinal (three patients) and cardiac abnormalities (three patients), unde- scended testes (four patients), and ocular abnormalities (one patient). clarify any clinical details, and patients were Increased numbers of pigmented naevi were examined clinically for extracolonic phenotypic common (fig 1), followed by telangiectasia of abnormalities. The following measurements the skin and mucous membranes, cutaneous were recorded for each patient where possible: and subcutaneous swellings, and skin pits on occipitofrontal circumference, distance be- the fingertips. One patient had a basal cell car- tween inner and distance between outer canthi, cinoma. http://jmg.bmj.com/ canthi. Those patients consenting to further Hypertelorism (13 cases) and macrocephaly investigations underwent x rays of the chest, (nine cases) were the commonest skeletal skull (anteroposterior and lateral views, includ- abnormalities present, and broad hands (fig 2), Table 1 Phenotypic abnormalities in 18 patients No Age Sex Skin Skeletal Neurological Cardiac Others Genetic syndrome 1 51 M Basal cell cancer, Bony cyst, hypertelorism - VSD - Gorlin syndrome on September 29, 2021 by guest. Protected copyright. naevi 2 41 M Penile Macrocephaly, hypertelorism, MR, - Patent vitello-intestinal duct, gut Bannayan-Riley-Ruvalcaba pigmentation broad hands hydrocephalus malrotation, cryptorchidism syndrome 3 5 F Skin pits Macrocephaly, hypertelorism, MR, PDA - ? broad thumbs/toes hydrocephalus 4 34 M Telangiectases Digital clubbing, hypertelorism Brain - Pulmonary AV fistulae, cyanosis Hered haemorrhagic abscess telangiectasia 5 35 M Naevi, lipomata Macrocephaly, hypertelorism, bifid MR, - Meckel's diverticulum, Gorlin syndrome rib, short metacarpals hydrocephalus cryptorchidism 6 12 M Penile & thigh - MR VSD Cryptorchidism Bannayan-Riley-Ruvalcaba pigmentation syndrome 7 41 M Telangiectases Macrocephaly, hypertelorism, - - Recurrent epistaxis ? Hered haemorrhagic broad hands telangiectasia 8 36 M Telangiectases Hypertelorism, broad hands - - Recurrent epistaxis ? Hered haemorrhagic telangiectasia 9 65 M Freckles - - Schatski ring 10 34 M Freckles Hypertelorism - - - 11 20 F Palmar nodules Prognathism, digital clubbing - - - 12 52 F - Digital clubbing, hypertelorism - - - 13 43 M - Macrocephaly, downward slanting - - - palpebral fissures 14 29 M - Hypertelorism, macrocephaly - - - 15 44 M Telangiectases, Hypertelorism, macrocephaly, - - Cryptorchidism, keratoconus pigmentation broad hands 16 22 F Hypertelorism, calcification of the - - - falx 17 27 M Telangiectases Macrocephaly 18 4 M - Hypertelorism, macrocephaly, Mental - Cleft palate, deafness, polydactyly retardation laryngomalacia VSD = ventricular septal defect, PDA = patent ductus arteriosus, MR = mental retardation. Patients 7 and 8 were two affected brothers. Patients 9 and 10 were from one family. Patients 12 and 16 were mother and daughter. 478 Desai, Murday, Phillips, et al Two patients had a
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