Article Text

Download PDFPDF

Delineation of a new syndrome: clustering of pyloric stenosis, endometriosis, and breast cancer in two families
  2. TUYA PAL,
  1. Breast Cancer Research, University of Toronto, 790 Bay Street, 750A, Toronto, ON M5G 1N8, Canada
  1. Professor Narod, steven.narod{at}

Statistics from

Editor—Familial tendencies have previously been observed for congenital pyloric stenosis, endometriosis, and breast cancer. These conditions have never been considered to have shared aetiological origins and consequently no previous attempts have been made to investigate an association. For example, when obtaining family history information for a child with pyloric stenosis, one would not routinely request a description of adult onset conditions such as endometriosis or breast cancer. Two families sharing an unusual clustering of these three conditions (pyloric stenosis, endometriosis, and breast cancer) were ascertained at the familial cancer clinics of the Women's College and Princess Margaret Hospitals in Toronto.

Family 1 (fig 1) contains four confirmed cases of breast cancer (below age 60), seven cases of endometriosis, five cases of congenital pyloric stenosis, nine cases of polycystic ovaries, and four cases of non-insulin dependent diabetes. In a second unrelated family, a woman previously diagnosed with premenopausal breast cancer, endometriosis, and pyloric stenosis reported one other case of congenital pyloric stenosis and four other cases of endometriosis in her family (fig 1). It is the similar and unusual presentation in these two families which suggests that the clustering of pyloric stenosis, endometriosis, and breast cancer may not be the result of chance.

Figure 1

Pedigrees of families 1 and 2. Proband is indicated by an arrow. The age of the subjects appears directly below symbol. CA = breast cancer followed by age of diagnosis (dx); Psu = primary site of cancer was not known; Pr CA = prostate cancer; Cx CA = cervical cancer; TAH = total abdominal hysterectomy; BSO = bilateral salpingo-oophorectomy; NIDDM = non-insulin dependent diabetes mellitus; CHD = congenital heart disease; D&C = dilatation and curettage; SA = spontaneous abortion; SB = stillbirth.

A family history of breast cancer is known to be the most significant risk factor for developing the disease. Approximately 5-10% of all cases are hereditary and accounted for by mutations in cancer susceptibility genes BRCA1 andBRCA2.1 2 Family 1 met our criteria for BRCA1 andBRCA2 testing, with four known cases of breast cancer diagnosed below the age of 60. Mutation analysis by direct sequencing of the coding regions of BRCA1 andBRCA2 as well as 1700 adjacent non-coding intronic base pairs was performed by Myriad Genetic Laboratories ( No BRCA mutation was identified for family 1. Family 2 was not tested forBRCA1 or BRCA2mutations.

The aetiology of endometriosis remains uncertain, although familial trends have been described.3 Four studies found that there is an increased risk among first degree relatives.4-7 A small twin study found 6/8 monozygotic and 0/2 dizygotic twin pairs had endometriosis.7 In family 2, five women in three generations had endometriosis and in family 1 seven women in three generations were given the diagnosis. The pattern of inheritance is consistent with sex limited, autosomal dominant inheritance.

A multifactorial genetic contribution for pyloric stenosis has been well established, although its pathological basis remains unknown. Twin studies have shown that there is a 25-40% concordance rate in monozygotic twins.8 9 Based on pooled data from several family studies and assuming a population prevalence of 0.3%, a relative risk for first degree relatives compared to the general population was 1810; however, population based studies (unselected patients) have not been done. Pyloric stenosis has recently been linked to the locus of the neuronal nitric oxide synthase (NOS1) gene, based on 27 families.11 The NOS1 locus was also examined for other multifactorial conditions such as asthma (candidate gene)13 14 and multiple sclerosis (no association).15 Family 1 has five documented cases of surgically corrected pyloric stenosis in three males and two females. Family 2 has a parent and child with PS, both female.

In addition to endometriosis, family 1 contains nine women with polycystic ovary syndrome (PCOS), including one woman with non-insulin dependent diabetes mellitus (NIDDM). PCOS and NIDDM have been shown to have a shared aetiology.12 Women with PCOS have a unique disorder of insulin action and are at increased risk of developing NIDDM, which occurs substantially younger (in the third to fourth decades) than it does in the general population.

Breast cancer, endometriosis, and pyloric stenosis in families 1 and 2 may be explained by separate genetic predispositions; however, the possibility that there is a common genetic basis exists. It is the complex interplay between environmental, hormonal, and genetic factors which poses a challenge to understanding the aetiology of each condition. A future study of pyloric stenosis in a case-control design may investigate any association with breast cancer or endometriosis.


View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.