Simultaneous presentation of Henoch Schonlein purpura in monozygotic twins

Henoch Schonlein purpura is a relatively common and well recognized paediatric condition. We report a case of 2 monozygotic twins that presented with typical Henoch Schonlein symptoms, starting simultaneously. Both children had positive throat cultures for Streptococcus pyogenes and skin biopsies typical for HS disease. Their genotype was determined and compared with studies suggesting predisposition according to HLA typing.     

Arrhythmogenic right ventricular cardiomyopathy in two pairs of monozygotic twins

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritant disease with an autosomal dominant mode of transmission with incomplete penetrance and variable expression. Linkage analysis in affected families succeeds in identifying 9 loci determining 9 subtypes of the disease. Genotype phenotype correlation is unclear and the influence of various environmental factors is discussed. OBJECTIVES: Genotype phenotype correlation in 2 pairs of monozygotic twins with ARVC and the role of environmental factors are analyzed. PATIENTS AND METHODS: Among 40 pts with ARVC and their 195 relatives there were 2 pairs of monozygotic twins: brothers, age 47 y; and sisters, age 48 y. History, ECG, Holter monitoring, 2D and Doppler Echo, and MRI were analyzed. RESULTS: Twin brothers: ARVC was diagnosed in the proband after the episode of VT with LBBB morphology (enlarged right ventricle, focal hypokinesia of apex, MR evidence of adipose tissue in RV wall). Identical morphology of RV was seen in asymptomatic twin brother. The patient presenting arrhythmia has been rowing for 4 years. Twin sisters: diagnosis was done during family screening. Both were asymptomatic. RV morphology typical for ARVC was found discrete in one of them (bulges adipose tissue in the RV apex); the latter showed changes suggesting RV abnormality (mild segmental dilatation of infundibulum, adipose tissue in a free wall of the RV). No differences in previous viral infections and sports involvement were observed. CONCLUSIONS: 1. Clinical picture of ARVC in monozygotic twins is not identical. 2. Strenuous effort may be a factor triggering the arrhythmia in pts with ARVC.     

Discordant clinical features of identical hypertrophic cardiomyopathy twins

Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects ∼1 in 500 individuals and is characterized by increased left ventricular wall thickness. While HCM is caused by pathogenic variants in any one of eight sarcomere protein genes, clinical expression varies considerably, even among patients with the same pathogenic variant. To determine whether background genetic variation or environmental factors drive these differences, we studied disease progression in 11 pairs of monozygotic HCM twins. The twin pairs were followed for 5 to 14 y, and left ventricular wall thickness, left atrial diameter, and left ventricular ejection fraction were collected from echocardiograms at various time points. All nine twin pairs with sarcomere protein gene variants and two with unknown disease etiologies had discordant morphologic features of the heart, demonstrating the influence of nonhereditable factors on clinical expression of HCM. Whole genome sequencing analysis of the six monozygotic twins with discordant HCM phenotypes did not reveal notable somatic genetic variants that might explain their clinical differences. Discordant cardiac morphology of identical twins highlights a significant role for epigenetics and environment in HCM disease progression.

Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy accompanied by nondilated ventricular chambers in the absence of other cardiac or systemic disease that would cause similar cardiac morphology (1). HCM is clinically recognized in ∼1 in 500 individuals, and >70% of familial HCM patients carry a pathogenic or likely pathogenic variant in genes encoding cardiac sarcomere proteins (2, 3) (denoted as HCM variants). Most HCM variants alter thick filament proteins myosin heavy chain 7 (MYH7) and myosin binding protein C (MYBPC3). Other HCM variants in genes encoding thin filament proteins, such as troponin T (TNNT2), account for a minority of cases (4, 5).HCM variants generally have high penetrance but produce variable expression of clinical manifestations (6–13). Some variant carriers manifest LV hypertrophy early in childhood, while others have normal LV wall thickness (LVWT) until the sixth or seventh decade of life. Hypertrophy can range from the upper limit of normal (LVWT = 12 mm) to massive (>30 mm) and can occur with minimal symptoms, advanced heart failure, or fatal arrhythmias (3, 10). Approximately 25% of patients die from HCM-related adverse events (14), including sudden cardiac death, thromboembolic stroke, and heart failure. Although patients with HCM variants have more adverse outcomes than patients with unknown causes for HCM (15, 16), the mechanisms accounting for diverse responses to variants within the same or different HCM genes are unknown.A classic approach to defining the contribution of genetic and environmental factors to variable progression of human disorders is to compare clinical phenotypes in monozygotic (MZ) twins, who have identical genome sequences. Few case reports have evaluated MZ twins with HCM (17–22). Wang et al. (19) showed that a twin pair with a pathogenic sarcomere gene mutation (MYH7 G768R) had similar LVWT but different amounts of fibrosis, measured by late gadolinium enhanced magnetic resonance imaging. Jansweijer et al. (22) examined interventricular septum thickness (IVSd) from 11 MZ twin pairs with HCM, including 5 pairs with sarcomeric variants, and found no significant heritability for IVSd in HCM. In contrast, a recent study demonstrated concordant morphologic findings and clinical course of identical twins with HCM, suggesting little environmental influence on clinical expression of HCM (20). Whether MZ twins with HCM variants have similar or different clinical courses remains uncertain. To more fully identify factors influencing HCM progression, we characterized longitudinal disease progression in 11 MZ twin pairs, including 9 with pathogenic sarcomere variants over 5 to 14 y.     

Identical twins with hypertrophic cardiomyopathy and apical aneurysm

Left ventricular apical aneurysms, in absence of coronary artery disease, occur in approximately 1% of patients with hypertrophic cardiomyopathy (HC). Identical twins, age 44 years, are presented with HC and identical LV morphology, including apical aneurysms. These cases demonstrate a genetic predisposition to the development of apical aneurysm, as well as overall LV morphology, in patients with HC.     

Different clinical course of ascending aortic aneurysm in monozygotic twins

A 45-year-old woman without medical history of cardiovascular disease came to the clinic. She was diagnosed as annuloectasia and aneurysm of ascending aorta and dissected aorta from above the aortic valve to renal artery level (type A). There are no laboratory abnormalities including CBC, biochemistry, and serology tests etc. She does not have any Marfanoid features. Surprisingly, when we reviewed her family history, we realized her monozygotic twin sister performed Bentall operation because of grade III/IV of aortic regurgitation due to annuloectasia and aneurysm of ascending aorta in our hospital 2 years ago. Now she underwent modified Bentall operation and recovered well. Our case suggests that physicians should meticulously check-up the first-order relatives of probands before dissection happens because familial thoracic aortic aneurysms tend to grow at a higher rate.     

Achalasia in monozygotic twins

Summary The familial occurrence of achalasia has been previously recorded and a genetic origin for the disease has been postulated. We present the first case of achalasia in monozygotic twins and suggest that concordance for the disease is consistent with a genetic factor in the etiology of achalasia.     

Focal myositis in monozygotic twins

Focal myositis is a rare disease with unknown etiology and a broad spectrum. Here, we present two cases in monozygotic twins who complained of recurrent pain of their calves and showed histological signs of inflammation and MRI image compatible with the diagnosis of focal myositis. The occurrence of twin cases not living in the same household suggests a genetic susceptibility to the disease.     

Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy

OBJECTIVES: The goal of this study was to assess gender-related differences in a multicenter population with hypertrophic cardiomyopathy (HCM). BACKGROUND: Little is known regarding the impact of gender on the heterogeneous clinical profile and clinical course of HCM. METHODS: We studied 969 consecutive HCM patients from Italy and the U.S. followed over 6.2 +/- 6.1 years. RESULTS: Male patients had a 3:2 predominance (59%), similar in Italy and the U.S. (p = 0.24). At initial evaluation, female patients were older and more symptomatic than male patients (47 +/- 23 years vs. 38 +/- 18 years; p < 0.001; mean New York Heart Association [NYHA] functional class 1.8 +/- 0.8 vs. 1.4 +/- 0.6; p < 0.001), and more frequently showed left ventricular outflow obstruction (37% vs. 23%; p < 0.001). Moreover, female patients were less often diagnosed fortuitously by routine medical examination (23% vs. 41% in male patients, p < 0.001). Female gender was independently associated with the risk of symptom progression to NYHA functional classes III/IV or death from heart failure or stroke compared with male gender (independent relative hazard 1.5; p < 0.001), particularly patients > or =50 years of age and with resting outflow obstruction (p < 0.005). Hypertrophic cardiomyopathy-related mortality and risk of sudden death were similar in men and women. CONCLUSIONS: Women with HCM were under-represented, older, and more symptomatic than men, and showed higher risk of progression to advanced heart failure or death, often associated with outflow obstruction. These gender-specific differences suggest that social, endocrine, or genetic factors may affect the diagnosis and clinical course of HCM. A heightened suspicion for HCM in women may allow for timely implementation of treatment strategies, including relief of obstruction and prevention of sudden death or stroke.     

Tetralogy of Fallot in monozygotic twins

A pair of monozygotic twins having tetralogy of Fallot is reported for the first time in the Indian literature. This case report will help in further enriching the existing data on genetic hypothesis of congenital heart defects.     

Occurrence of scleroderma in monozygotic twins

Familial occurrence of scleroderma is rare and concordance for the disease in twins has been reported exceptionally. We describe 2 female identical twin pairs concordant for scleroderma. The first twin pair was diagnosed with the systemic form of scleroderma, the second pair with the localized form.