Aplasia cutis congenita type VII of the lower extremity: a favourable disease course with minimal conservative treatment.

Aplasia cutis congenita (ACC) is a group of rare heterogeneous disorders characterised by absent areas of skin at birth. The majority of cases involve the scalp region. ACC limited to one lower limb is extremely rare. We report an usual case of ACC limited to the left thigh of which healing occurred in utero. The case was managed conservatively and the disease course has been favourable with no limitations in limb function and an entirely normal development. Most cases of ACC are self-healing, justifying a conservative approach. This holds further true for ACC limited to one lower limb where the majority of cases reported to date show a favourable disease course with minimal conservative treatment.

Two SMARCAD1 Variants Causing Basan Syndrome in a Canadian and a Dutch Family.

Basan syndrome is an autosomal dominant genodermatosis characterized by congenital adermatoglyphia, transient congenital facial milia, neonatal acral bullae, and absent or reduced sweating. Basan syndrome is rare and has been reported in only 10 kindreds worldwide. It is caused by variants in the skin-specific isoform of SMARCAD1, which starts with an alternative exon 1. All reported variants, except for one large deletion, are point mutations within the donor splice site of the alternative exon 1. In this paper, we report two families with Basan syndrome and describe two SMARCAD1 variants. In one family, we have identified a complex structural variant (a deletion and a nontandem inverted duplication) using whole-genome optical mapping and whole-genome sequencing. Although this variant results in the removal of the first nine exons of SMARCAD1 and exon 1 of the skin-specific isoform, it manifested in the typical Basan phenotype. This suggests that unlike the skin-specific isoform, a single copy of full-length SMARCAD1 is sufficient for its respective function. In the second family, whole-exome sequencing revealed a deletion of 12 base pairs spanning the exon‒intron junction of the alternative exon 1 of the skin-specific SMARCAD1 isoform. In conclusion, we report two additional families with Basan syndrome and describe two SMARCAD1 pathogenic variants.

Acitretin induces capillary leak syndrome in a patient with pustular psoriasis.

Capillary leak syndrome is a rare and potentially life-threatening condition caused by a shift of intravascular fluid and proteins to the interstitial space. We describe a patient with pustular psoriasis in whom capillary leak syndrome developed after the start of acitretin. Immediate withdrawal of retinoic acid is necessary and corticosteroid therapy should be considered.

Lower birth weight predicts metabolic syndrome in young adults: the Atherosclerosis Risk in Young Adults (ARYA)-study.

OBJECTIVE: To study the relationship between intrauterine growth and the metabolic syndrome, particularly fasting serum lipids in young adulthood. METHODS: Seven hundred and forty-four young adults aged 26-31 years participated in the ARYA birth cohort. Birth characteristics were available from charts kept by the Municipal Health Service, Utrecht, The Netherlands. Adult medical history and lifestyle information were assessed by questionnaires. Adult anthropometry, blood pressure, fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides were measured, and LDL-cholesterol was calculated. RESULTS: Subjects in the lower tertiles of birth weight (1250-3209 and 3210-3649 g) had higher risks for metabolic syndrome than those in the highest birth weight tertile (3650-5500 g): odds ratio, 1.8; 95% confidence interval (CI) 1.0-3.5 and 1.4; 0.7-2.7, respectively; p for trend = 0.064, adjusted for gender, cardiovascular disease family history and current education. Birth weight was inversely related to systolic blood pressure (linear regression coefficient, -1.9 mmHg/kg birth weight; 95% CI -3.4 to -0.3) and to (log) triglycerides in mmol/L (-0.03/kg birth weight; 95% CI -0.06 to -0.01), adjusted for gender, current body mass index and current education. Birth weight showed inverse relations to diastolic blood pressure, serum glucose, total and LDL cholesterol and positive relations to waist circumference and HDL cholesterol levels, although not statistically significant. Birth length and ponderal index were not related to the metabolic syndrome or lipid profiles. CONCLUSION: Lower birth weight indicates a higher risk for metabolic syndrome in young adults, particularly through higher serum triglycerides and higher systolic blood pressure.

Alcohol intake and aortic stiffness in young men and women.

BACKGROUND: Moderate alcohol consumption has been shown to protect against cardiovascular disease. Aortic stiffness can be regarded as a marker of cardiovascular disease risk. Previously we have shown an inverse to J-shaped association between alcohol intake and aortic stiffness in middle-aged and elderly men and postmenopausal women. OBJECTIVE: In the present study we examined whether a relation between alcohol intake and aortic stiffness is already present at a younger age. DESIGN: Cross-sectional data of a cohort study in men and women aged 28 years were analysed stratified by gender (240 men and 283 women). MEASUREMENTS: Alcohol intake was derived from a questionnaire and aortic stiffness was assessed by pulse-wave velocity measurement. RESULTS: In women an alcoholic beverage intake of >/=1 glass/day is associated with a 0.36 m/s (95% confidence interval, -0.58 to -0.14) lower pulse-wave velocity compared with non-drinkers. In men alcohol intake is also inversely related to pulse-wave velocity, but this was not significant. These findings were independent of age, blood pressure and heart rate. CONCLUSIONS: These findings suggest that moderate intake of alcohol may affect vascular stiffness at an early age, notably in women. These findings may be viewed as compatible with a vascular protective effect of alcohol that expresses well before the occurrence of symptomatic cardiovascular disease.

Birth weight and carotid intima-media thickness: new perspectives from the atherosclerosis risk in young adults (ARYA) study.

PURPOSE: Although intrauterine growth retardation (IUGR) is associated with increased risk of cardiovascular disease (CVD) in adult life, it is unclear whether the relationship is present at younger ages. Furthermore, current debate suggests that postnatal factors might be at least as important as prenatal conditions. The authors investigated whether low birth weight leads to an increased risk of subclinical atherosclerosis in a population-based sample of 750 Dutch men and women, aged 27 to 30 years. METHODS: Information about birth characteristics was available from the original charts of the Municipal Health Service, Utrecht, The Netherlands. Cardiovascular risk factors were evaluated by a questionnaire. The extent of atherosclerosis, assessed by carotid intima-media thickness (CIMT), was measured in both common carotid arteries. RESULTS: Overall, birth weight was not related to common CIMT. However, in the lowest tertile of birth length an inverse association between birth weight and common CIMT was observed. Moreover, low birth weight was significantly associated with increased common CIMT in those who showed exaggerated postnatal growth. CONCLUSIONS: These findings suggest that low birth weight is only associated with increased common CIMT in young adulthood in those who experienced severe IUGR and in those who showed exaggerated postnatal growth.

Does a routinely measured blood pressure in young adolescence accurately predict hypertension and total cardiovascular risk in young adulthood?

BACKGROUND: It is insufficiently known if routine blood pressure (BP) measurement by school doctors has added predictive value for later hypertension and cardiovascular risk. OBJECTIVE: To assess whether screening of BP in adolescence has additional predictive value to already routinely collected indicators of later hypertension and cardiovascular risk. METHODS: In the Dutch city of Utrecht, routine BPs and anthropometry were collected from school health records of 750 adolescents. In The Hague, standardized repeated BP measurements and anthropometry were available for 262 adolescents. Of both cohorts, 998 now young adults were recently re-examined. Predictors of adult hypertension, systolic blood pressure (SBP) > or = 140 mmHg and/or diastolic blood pressure (DBP) > or = 90 mmHg) and 10-year cardiovascular risk were analysed by logistic regression and area under receiver operator characteristics curve (AUC). RESULTS: A total of 167 young adults had hypertension. Single adolescent SBP and DBP predicted hypertension: odds ratio (OR) 1.04 per mmHg [95% confidence interval (CI): 1.03-1.06], OR 1.02 (1.00-1.04), respectively, but with little discriminative power. Gender, adolescent body mass index (BMI) and age combined predicted hypertension: AUC 0.71 (0.67-0.75), which slightly improved by adding SBP: AUC 0.74 (0.70-0.77); difference in AUC 0.03 (0.002-0.06). SBP exclusively predicted hypertension within men: OR 1.03 (1.01-1.04), AUC: 0.59 (0.53-0.65), and within women: OR 1.08 (1.05-1.11), AUC 0.74 (0.67-0.82). However, an adolescent BP of > or = 120 mmHg did not efficiently detect hypertensive men, while it detected 57.9% of hypertensive women. Only young adult men had meaningful 10-year cardiovascular risks, which only SBP predicted: OR risk score > 95th percentile 1.04 (1.02-1.07), AUC 0.67 (0.60-0.75). CONCLUSION: A single routine BP measurement in adolescent girls efficiently predicts young adult hypertension. In adolescent boys, BP predicts young adult 10-year cardiovascular risk.

Cardiovascular risk factors and increased carotid intima-media thickness in healthy young adults: the Atherosclerosis Risk in Young Adults (ARYA) Study.

BACKGROUND: The relation between cardiovascular risk factors and extent of atherosclerosis in middle-aged and elderly populations is well established. Autopsy studies have suggested that similar associations may be present at a young age. We evaluated the relationship between conventional risk factors and increased carotid intima-media thickness (CIMT) in 750 healthy young adults, aged 27 to 30 years. METHODS: All participants completed a questionnaire on cardiovascular risk factors, had a fasting blood sample drawn, and underwent an ultrasonographic examination of both common carotid arteries to assess common CIMT (CCIMT). RESULTS: Age (11.2 micro m/SD), body mass index (10.3 micro m/SD), pulse pressure (5.0 micro m/SD), sex (4.8 micro m/SD), and low-density lipoprotein cholesterol level (4.3 micro m/SD) were independent determinants of increased CCIMT in young adults (R2 = 0.36). Total pack-years of smoking, adjusted for age and sex, showed a linear trend with increased CCIMT (P =.02), which attenuated after further adjustment for body mass index. Common CIMT increased gradually and significantly with the number of cardiovascular risk factors present. The estimated absolute risk, based on the Framingham risk function, for development of coronary heart disease within 20 years was 2.5 times higher in individuals with mean CCIMT in the highest quartile compared with those in the lowest quartile of the distribution. CONCLUSIONS: An unfavorable cardiovascular risk profile is associated with a marked increase in CCIMT in young adulthood. Efforts to change modifiable risk factors early in life may retard atherosclerosis development and hence delay the onset of clinical cardiovascular disease later in life.

Adolescent blood pressure and blood pressure tracking into young adulthood are related to subclinical atherosclerosis: the Atherosclerosis Risk in Young Adults (ARYA) study.

BACKGROUND: Increased blood pressure (BP) in young adulthood is associated with cardiovascular morbidity and mortality. Longitudinal studies of patients at young ages are, however, limited. Our aim was to study the relationships of adolescent BP and tracking of BP into young adulthood with subclinical atherosclerosis, as assessed by carotid intima-media thickness (CIMT), at the age of 28 years. METHODS: The Atherosclerosis Risk in Young Adults (ARYA) study comprises of a community-based sample of 750 subjects aged 27 to 30 years. In the 352 men and 398 women, at least one BP measurement was recorded at a mean age of 13 years in school health records. Recently, all participants completed a questionnaire on cardiovascular risk factors, had a fasting blood sample drawn, and underwent an ultrasound examination of both common carotid arteries to assess CIMT. RESULTS: Linear regression showed that adolescent systolic BP was associated with thickening of the intima-media (an increase of 7.5 microm in CIMT per standard deviation increase in systolic BP; 95% CI 4.3 to 10.6). Similar relations were found for pulse pressure and mean arterial pressure. When sex, age, and body mass index at adolescence and young adulthood and adult BP were taken into account, the relations attenuated, but for pulse pressure they remained statistically significant. Furthermore, subjects who tracked in the highest systolic BP and pulse pressure levels from adolescence into young adulthood showed the thickest CIMT. CONCLUSION: Our findings strengthen the notion that elevated BP at adolescence and a relative increase in BP from adolescence to adulthood unfavorably affect cardiovascular risk, as indicated by increased CIMT.

Adolescent blood pressure does not predict aortic stiffness in healthy young adults. The Atherosclerosis Risk in Young Adults (ARYA) study.

BACKGROUND: Increased arterial stiffness has been shown to be a good predictor of cardiovascular morbidity and mortality and to be associated with an adverse cardiovascular risk profile. OBJECTIVE: To evaluate the relationship between adolescent blood pressure and aortic stiffness in 524 healthy young adults aged 27-30 years, as a means of investigating early determinants of arterial stiffness. SETTING: General community. PARTICIPANTS: We studied 524 healthy young adults, aged 27-30 years, who attended secondary school in Utrecht, The Netherlands. MEASUREMENTS: Data on adolescent weight, height, blood pressure and stage of puberty were available from the original school health records of the Municipal Health Service. At young adulthood, a questionnaire on cardiovascular risk factors was completed and a fasting blood sample was drawn. MAIN OUTCOME MEASURE: Arterial stiffness, assessed by carotid-femoral pulse wave velocity (PWV). RESULTS: Adolescent blood pressure did not predict aortic PWV at young adulthood (linear regression coefficient 0.03 m/s per 10 mmHg increase in systolic blood pressure; 95% confidence interval 0.09 to 0.14). Repeated analysis in a subgroup (n = 199) for whom two adolescent blood pressure measurements were averaged showed stronger (2-19x) associations with adult PWV, although these were not significant. CONCLUSION: Adolescent blood pressure did not predict arterial stiffness in healthy young adults. Measurement error in the baseline blood readings (regression to the mean phenomenon) may partly explain the lack of association in our study. Further studies should confirm our results in order to enable better understanding of the role of adolescent blood pressure in the aetiology of vascular damage.

Gestational age and birth weight in relation to aortic stiffness in healthy young adults: two separate mechanisms?

BACKGROUND: Impaired vascular development due to intrauterine growth retardation and postnatal-induced vascular damage by an unfavorable cardiovascular risk profile may both cause stiffer arteries in later decades. METHODS: Of 524 young adults, participating in the Atherosclerosis Risk in Young Adults (ARYA) study, data on birth characteristics were obtained from the original medical records of the Municipal Health Service and the extent of aortic stiffness was assessed using carotid-femoral pulse wave velocity (PWV). RESULTS: The PWV showed an inverse trend with gestational age (linear regression coefficient (beta) = -0.07 m/sec per 1 week; P =.064) whereas it was positively related to birth weight (beta = 0.33 m/sec per 1 kg; P =.020), adjusted for blood pressure (BP), gender, age, and each other. After exclusion of the 26 prematurely born infants, the association with gestational age was attenuated (beta = -0.03 m/sec per 1 week; P =.582), whereas the relation with birth weight hardly changed (beta = 0.30 m/sec per 1 kg; P =.041). In an analysis in which we excluded the 26 subjects with diabetic mothers the birth weight-PWV relation was attenuated (beta = 0.21 m/sec per 1 kg; P =.169). CONCLUSIONS: Our findings suggest that prematurity drives the relation of gestational age and PWV, whereas risk of impaired glucose tolerance drives the relation of birth weight and PWV. We hypothesized that two separate mechanisms might be involved in the development of arterial stiffness in healthy young adults.