Anticipation in familial Crohn's disease

B Grandbastien,^a M Peeters,^b D Franchimont,^c C Gower-Rousseau,^a D Speckel,^a P Rutgeerts,^b J Belaïche,^c A Cortot,^a R Vlietinck,^d J-F Colombel^a

^a Registre des Maladies Inflammatoires du Tube Digestif du Nord-Ouest de la France (EPIMAD), Service D'Hépato-Gastroentérologie, Hôpital Huriez, CH et U Lille, France, ^b Department of Gastroenterology, University of Leuven, Belgium, ^c Service d'Hépato-Gastroentérologie, CHU Liège, Belgium, ^d Genetic Epidemiology, Department of Human Genetics, University of Leuven, Belgium

Correspondence to: Dr Colombel.

Accepted for publication 30 September 1997

BackgroundOffspring with a family history of Crohn's disease have an earlier age of onset than their parents. This might be due to genetic anticipation, characterised by earlier and/or more severe disease in subsequent generations.
AimsTo investigate the possibility of genetic anticipation in affected parent-child pairs with Crohn's disease from France and Belgium.
Patients and methodsIn a cohort of 160 multiply affected families with Crohn's disease, 57 parent-first affected child pairs were detected. Clinical characteristics (age at diagnosis, disease extent, and type) of both parents and children were registered and compared.
ResultsChildren were younger than their parents at diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p<0.0001). However, the difference was related to the age at diagnosis in the parents and was not present in 12 parent-child pairs with an early age at diagnosis for the parents. In most cases, disease extent and type were not considered more severe in children than in parents. Parental sex affected neither age at diagnosis nor extent and type of disease in children.
ConclusionPatients in the second affected generation acquire their disease at an earlier time in life in some but not all familial cases of Crohn's disease. Several explanations including genetic anticipation and environmental factors might explain this phenomenon.
(GUT 1998;42:170-174)

Keywords: Crohn's disease;  familial;  genetic anticipation