Discrete membranous subaortic stenosis in siblings

Abstract

References E1 Habbal MH (1991) Discrete subaortic stenosis in a newborn. PediatrCardiol 12 : 243-244 2. Gale AW, Cartmill TB, Bernstein L (1974) Familial subaortic membranous stenosis. Aust NZ J Med 4:576-581 3. Gewillig M, Daenen W, Dumoulin M, Van der Hauwaert L (1992) Sir: Discrete membranous subaortic stenosis (DMSS) is an uncommon cardiac defect occurring mostly as an isolated lesion of obscure aetiology [3]. We investigated two sisters affected by DMSS whose parents were unaffected, but were second cousins suggesting autosomal recessive inheritance.The first child was born at term by Caesarian section following an uncomplicated pregnancy. Her birth weight was 3750g. She underwent two-dimensional echocardiography at the age of 4 years because of a heart murmur. A diagnosis of DMSS was suggested. Echocardiography with Doppler examination at 11 years confirmed DMSS and showed mild aortic regurgitation with a left ventricle-aortic gradient of 60 mm Hg. At 11 years of age this defect was successfully corrected. No additional major defect or significant dysmorphism was noted.The second affected sister was evaluated at 3 years of age. Apart from a heart murmur, physical examination was unremarkable. Neurological development was normal. Two-dimensional and Doppler echocardiography revealed a DMSS with a 45 mm Hg gradient between the left ventricle and aorta and trivial aortic regurgitation.We are aware of other families with DMSS in which affected sibs were born to unaffected parents [2,7]. In each of three families there were two affected children [2,7], while in one family DMSS occurred in three sibs [7]. Parental consanguinity has been documented in two published families [7] and in the present family. In two other families DMSS occurred in the mother and daughter and in the uncle and nephew [6]. In addition, recurring left ventricular outflow tract obstructions have also been found in relatives of patients with DMSS [4].Although the diagnosis of DMSS in the neonatal period is rare [1] and the lesion usually develops later, familial aggregation, parental consanguinity, and breeding experiments in Newfoundland dogs [5] have favoured a genetic origin of the disease. Familial recurrence of DMSS in at least five pairs of siblings, the concordance of an anatomical defect in familial cases, and the third and fifth degree relationships found in three families indicate an autosomal recessive inheritance in some cases. This suggestion has obvious implications for genetic counselling.Abbreviation." DMSS = discrete membranous subaortic stenosis

Genetics of canine subvalvular aortic stenosis (SAS)

“…Previously published studies have demonstrated that the mode of inheritance for SAS in dogs is complex and variable [ 5 , 6 ]. This is similar to humans, in which an autosomal recessive as well as an autosomal dominant mode of inheritance was reported previously [ 18 – 20 ]. In dogs, pedigree evaluation was also completed for other dog breeds, with a high prevalence for this disease [ 33 ].…”

Thoughts about fixed subaortic stenosis in man and dog

“…30,65,66,[77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93] Other supportive findings include the fact that some cases, admittedly uncommonly, are diagnosed in the neonatal period, [86][87][88][89] there is well-recognised recurrence in siblings, 84 and the fact that some patients with fixed subaortic stenosis have been born to nonaffected but consanguineous parents. On the basis of these observations, it has been suggested that fixed subaortic stenosis could be the result of an autosomal recessive mutation 90,91 (Table 2). From the stance of the dog, Patterson, his colleagues, and others, have discussed extensively the epidemiologic and genetic aspects of cardiovascular development, [4][5][6][7]10,94,95 while Mulvihill and Priester 97 have reiterated the similarities between canine and human congenital cardiac disease.…”

The mendelian basis of congenital heart defects

“…12 The ever increasing number nowadays of patients with severe defects surviving surgical intervention have also shown that the incidence of cardiac malformations in the offspring of affected parents is higher than had been previously expected, supporting a proposed monogenic inheritance for many cardiac defects. 13 A mendelian transmission has been identified for some specific isolated cardiac malformations, including hypertrophic cardiomyopathy, 14 supravalvar aortic stenosis, 15 "conotruncal" defects, 16 ' 17 atrioventricular canal defects, 18 -19 discrete subaortic stenosis, 20 and patency of the arterial duct. 21 It has now become possible to delineate the genetic defect of such familial cardiac malformations through linkage analysis and positional cloning.…”