Genome-wide analysis of mitral valve disease in Cavalier King Charles Spaniels.

The Cavalier King Charles Spaniel (CKCS) is prone to severe early onset mitral valve disease. In this study, 36 purebred CKCS dogs were evaluated for mitral valve murmur and divided into early and late onset groups. A genome-wide genetic approach was used to assess whether the condition is determined by a small number of genetic factors. There were no regions of highly discrepant homo/heterozygosity in the two groups. Similarly, there was no evidence for loci associated with mitral valve murmur in a genome-wide association study. This analysis suggests that familial occurrence of mitral valve murmur in the CKCS breed is not due to a single major gene effect, indicating that breeding strategies to eliminate the disease cannot be based on genotype information at this time.

Heritability of premature mitral valve disease in Cavalier King Charles spaniels.

Mixed model analysis of 1252 records of cardiac auscultation of 4- to 5-year-old Cavalier King Charles spaniels (CKCS) from 1991 to 2008 in conjunction with the Kennel Club pedigree records of all dogs registered from the mid 1980s to September 2007 was used to estimate variance parameters of premature mitral valve disease (MVD). Data were limited to dogs ≥4 and <5 years of age to ensure diagnostic distinction between early and late onset MVD. Cardiac murmurs were detected in 108/1252 (8.6%) dogs. Heritability estimates of 0.67 (standard error, SE 0.071) for the grade of murmur and 0.33 (SE 0.072) for the presence/absence of murmur were calculated. The variance due to clinician was 0.02 (SE 0.012) for grade and 0.03 (SE 0.017) for presence/absence of murmur. These results indicate that the presence and severity of MVD, as assessed by cardiac auscultation, in 4- to 5-year-old CKCS is highly heritable and that selection against the disease should be successful.

Evaluation of the Swedish breeding program for cavalier King Charles spaniels.

A breeding program with the aim of reducing the prevalence of mitral regurgitation (MR) caused by myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) is currently ongoing in Sweden. In this investigation 353 CKCS were selected as a sample of the population and 150 were examined by auscultation for heart murmurs when they reached the age of six years in 2007 and 2009. The aim with this investigation was to study the prevalence of heart murmurs in six-year-old CKCS and to estimate if prevalence has decreased since the breeding program was introduced 2001. The effect of the breeding program was evaluated by comparing the prevalence of heart murmurs in the two groups. In 2007, the prevalence of heart murmurs was 52% (50% for females and 54% for males) and in 2009, the prevalence was 55% (44% for females and 67% for males). No significant difference was found in the prevalence of heart murmurs between 2007 and 2009 (P=0.8). For all six-year-old CKCS, the prevalence of heart murmur was 53% (females 46% and males 61%), which is higher than previous Swedish investigations.

Congenital heart disease in boxer dogs: results of 6 years of breed screening.

The aim of this study was to analyse the results of 6years (1999-2004) of mandatory breed screening for congenital heart disease in Boxer dogs using physical examination and echocardiography. Records of 1283 Boxers were reviewed and 165 dogs (12.86%) were found to be affected by heart disease, with aortic and pulmonic stenosis being the most frequent cardiac lesions. Comparison of these results with those of a previous survey showed a lower overall prevalence of both outflow obstructions, particularly of the more severe forms. A male predisposition for both aortic and pulmonic stenosis was evident from the study. Consistent with reports from other countries, soft left basilar heart murmurs were detected in both healthy dogs and dogs affected with congenital heart disease.

[Evaluation of cardiac murmurs in children]. / Vurdering av barn med hjertebilyder.

BACKGROUND: Many normal children have heart murmurs, but most children do not have heart disease. Differentiation of innocent murmurs from those due to structural heart disease, pathological murmurs, is largely clinical. MATERIAL AND METHODS: This review is based upon the authors' own studies and PubMed searches. RESULTS: An appropriate history and a properly conducted physical examination can identify children at risk of significant heart disease. INTERPRETATION: If a murmur cannot clearly be labelled as innocent based on characteristics like sound quality, intensity, location and response to posture, then referral to a paediatric cardiologist is indicated. Other indications for referral are any sign or symptom of cardiovascular disease such as shortness of breath, cyanosis or decreased exercise tolerance. In addition, children with syndromes should, because of their high risk of congenital heart disease, be referred to a paediatric cardiologist for further evaluation.

Complex congenital heart malformations in mosaic tetrasomy 8p: case report and review of the literature.

We describe a 5-month-old boy with complex congenital heart defects (dTGA, DORV, VSD, ASD, and PDA), minor facial and ear anomalies, deep palmar creases, multiple vertebral anomalies, agenesis of the corpus callosum, and mosaic tetrasomy 8p (47,XY,+i(8)(p10)[88%]/46,XY[12%] in blood with normal chromosomes in cultured skin fibroblasts. This infant represents the eleventh reported case of mosaic tetrasomy 8p since its first description by Kristofferson et al. [1988: Clin Genet 34:201-203]. The pattern of heart malformations and discordance of blood and fibroblast karyotypes make our case unique. Our report and review suggest that an important distinction between mosaic tetrasomy 8p and other chromosome 8 aneuploidies involves the increased incidence and complexity of congenital heart malformations.

Relationship between parental cardiac status in Cavalier King Charles spaniels and prevalence and severity of chronic valvular disease in offspring.

OBJECTIVE: To study the relationship between parental cardiac status in Cavalier King Charles Spaniels and development of chronic valvular disease (CVD) in offspring. DESIGN: Historical cohort. ANIMALS: 54 female and 53 male Cavalier King Charles Spaniel offspring. PROCEDURE: 7 sires, selected on the basis of their liability to develop CVD, were screened for clinical signs of CVD and assigned to 1 of 3 groups (late, intermediate, and early onset of CVD). The mates of these sires (30 dams) were selected and classified likewise, and 107 offspring produced in 1988 from matings between these parents were screened for clinical signs of CVD at a mean age of 5.3 +/- 0.3 years. RESULTS: 55% of the offspring were free from clinical signs of CVD, whereas 45% had cardiac murmurs of low or moderate intensity. The proportion of offspring with heart murmurs and the intensity of murmurs were significantly greater with increased parental classification. More males than females had developed murmurs, and murmurs of moderate intensity also were more prevalent in males. Results of multiple-regression analysis indicated that mean parental classification and sex had significant effects on proportion of offspring with murmurs and their intensity. Additionally, age affected disease prevalence and severity, despite the narrow range in age of offspring examined. CLINICAL IMPLICATIONS: Parental CVD status is an important factor influencing the probability of heart murmurs and their intensity in offspring. The results of this study indicate that CVD development is a polygenic threshold trait and that sex of the offspring influences threshold levels.

Microdeletion of chromosome 7P syndrome ocular manifestations.

Several syndromes have been associated with microdeletions of the autosomes. These syndromes are diverse in their morphology and frequently manifest abnormalities of the ocular adnexa. A child with an uncommon microdeletion of the short arm of chromosome 7P presented initially with congenital myogenic ptosis. After multiple systemic abnormalities were found during a routine examination, the child was referred for genetic evaluation where the defects were incidentally found. The child responded well with a fascia lata frontalis sling. The genetic disorder is discussed with an emphasis on the ophthalmologic findings.

Mild phenotypic manifestation of a 7p15.3p21.2 deletion.

A 28 month old girl with dysmorphic features was found to have an interstitial deletion of the short arm of chromosome 7p15.3-7p21.2. The patient had ptosis, dacryostenosis, pectus excavatum, short hands, and her development was normal or mildly delayed. Craniosynostosis and growth retardation, which were present in two other patients with similar deletions, were not present. Because of the mild manifestations, this case expands the clinical spectrum of the 7p15-7p21 deletion phenotype.

Chronic valvular disease in the cavalier King Charles spaniel in Sweden.

The prevalence of chronic valvular disease was studied in 494 cavalier King Charles spaniels with a mean (+/- sd) age of 3.0 +/- 2.7 years. Cardiac murmurs were detected in 65 (13.2 per cent) of the dogs. Among 61 cavalier King Charles spaniels with a mean age of 6.4 +/- 2.8 years, cardiac murmurs were detected in 32 (52 per cent). In both groups of dogs the prevalence of cardiac murmurs was low among dogs younger than three years (1.9 per cent) but increased with age (P < 0.001). The estimated ages at which 50 per cent of the dogs had developed murmurs were 7.5 and 6.2 years, respectively. When 39 of the 61 dogs were re-examined three years later, cardiac murmurs were detected in 28 (72 per cent), and the intensities of the murmurs had generally increased (P < 0.05). Nine (28 per cent) of the dogs which had previously had murmurs had been euthanased for signs of congestive heart failure whereas none of the dogs which had been free of murmurs had died from congestive heart failure. Animal insurance statistics from 1982 to 1990 (1983 excluded) for dogs less than 10 years old showed that claims for veterinary care or death or euthanasia were five times more common in the cavalier King Charles spaniel than in dachshunds (P < 0.001) and eight times more common than the mean for all other insured breeds (P < 0.001).

Familial fixed subaortic stenosis.

In this report, we give details of two families in which fixed subaortic stenosis was found in more than one member. It is rare for this entity to show familial incidence.

Autosomal dominant atrial septal defect of ostium secundum type. Report of three families.

The authors report on three Sicilian families with 17 individuals (10 females and 7 males) in successive generations affected by atrial septal defect of ostium secundum type (S-ASD) without conduction defect. The anomaly was inherited as an autosomal dominant trait. Cytoplasmic inheritance could be excluded, the anomaly being transmitted also by fathers. Familial S-ASD is probably more frequent than commonly reported since cardiological examination of the relatives is not routinely performed in every case of apparently sporadic ASD.