Alojz Gregorič

A diagnostic approach for the child with hypertension

Hypertension during childhood is not rare, with an estimated prevalence of between 1% and 2%, although it is often an underrecognized clinical entity. Elevated blood pressure may be a sign of underlying disease or it may represent early onset of essential hypertension. In recent years the measurement of blood pressure has been emphasized as an important component of the routine pediatric physical examination that enables early detection of children with hypertension. In the evaluation of the child with documented blood pressure elevation, confirmation of truly and persistently elevated blood pressure is of the utmost importance. In addition, a thorough history and a full clinical examination are essential. These are followed by appropriate investigations, which are tailored to the age of the child and to the severity of the blood pressure elevation. Investigations should not only focus on a search for the underlying cause, but also on establishing effects on target organs, complications or additional diseases and on assessment of the total cardiovascular risk to the individual patient. An algorithm, which is a valuable diagnostic tool for the diagnosis and management of the child with hypertension, is presented. All children with confirmed hypertension need long-term follow-up, counseling and treatment. In those cases where an underlying cause of the hypertension is detected, the established diagnosis then determines the specific therapy and management.

Self-reported Adherence Behavior in Adolescent Hypertensive Patients: The Role of Illness Representations and Personality

OBJECTIVE This exploratory study examined the role that illness representations and personality play in the various adherence behaviors of adolescents diagnosed with essential hypertension. METHODS The participants were 97 hypertensive adolescents. They completed self-report questionnaires pertaining to (1) demographic and medical data, (2) adherence, (3) illness representations, and (4) personality. Medical charts were also assessed. RESULTS The hierarchical regression analyses indicated that: (1) conscientiousness, agreeableness, and perception of treatment effectiveness account for a significant amount of variance in general adherence; (2) perception of treatment effectiveness is predictive of overall specific adherence; and (3) for adherence to most of the individual specific regimen recommendations, illness representations are more predictive compared to personality dimensions. CONCLUSIONS The personality domains of conscientiousness, extraversion, agreeableness, and illness representation dimensions (treatment control, concern, and emotional burden) were shown to predict adherence behaviors in adolescent hypertensive patients differentially. Study implications and limitations are discussed.

Metabolic syndrome in the pediatric population: a short overview

The metabolic syndrome (MS) in adults is defined as a concurrence of obesity, disturbed glucose and insulin metabolism, hypertension and dyslipidemia, and is associated with increased morbidity and mortality from cardiovascular diseases and type 2 diabetes. Studies now indicate that many of its components are also present in children and adolescents. Moreover, the clustering of these risk factors has been documented in some children, who are at increased cardiovascular risk in adulthood. The MS is highly prevalent among overweight children and adolescents. Identifying these children is important for early prevention and treatment of different components of the syndrome. The first-line treatment comprises lifestyle modification consisting of diet and exercise. The most effective tool for prevention of the MS is to stop the development of childhood obesity. The first attempt at consensus-based pediatric diagnostic criteria was published in 2007 by the International Diabetes Federation. Nevertheless, national prevalence data, based on uniform pediatric definition, protocols for prevention, early recognition and effective treatment of pediatric MS are still needed. The aim of this article is to provide a short overview of the diagnosis and treatment options of childhood MS, as well as to present the relationships between MS and its individual components.

Carotid artery intima‐media thickness and angiotensin‐converting enzyme gene polymorphism in the offspring of parents with premature stroke

Aim: To determine some common cardiovascular risk factors, alterations in the measurements of intima‐media thickness (IMT) and the distribution of the angiotensin‐converting enzyme (ACE) polymorphism in children of parents with premature stroke, and to investigate the cardiovascular risk of these children and the potential need for some preventive measures.Methods: A family history of cardiovascular disease represents a cardiovascular risk factor in the offspring. This association has not yet been clearly determined for cerebrovascular accidents. New technology allows us to investigate the risk for cardiovascular disease at an early presymptomatic stage. We applied the measurement of IMT of carotid arteries by ultrasound imaging and the determination of the ACE insertion/deletion (I/D) polymorphism in blood to evaluate the predisposition for cerebrovascular disease in the offspring of patients with previous stroke. We investigated 58 subjects whose parents had experienced a cerebrovascular accident before the age of 45 y and compared them with a matched control group whose parents had not suffered a stroke. Results: The results of IMT at various sites of the carotid arteries and the genotype distribution of the ACE gene were not significantly different between the study group and the control group. In addition, no differences were found in the serum levels of lipid fractions or other biochemical variables.

Polymorphisms in four candidate genes in young patients with essential hypertension

Aim: To determine whether four potential genetic factors (polymorphisms in genes for alpha-adducin, beta-adducin, the G-protein beta-3 subunit and nitric oxide synthase) are important for the development of essential hypertension (EH) in Slovenian children and young adults with EH. Methods: Both a nuclear families approach and case-control study have been performed. Genotyping of common polymorphisms in these genes using polymerase chain reaction was carried out in 104 nuclear families (an affected child, both parents) and in 200 control patients. Results: Using the transmission disequilibrium test, no statistically significant differences were found between the frequencies of transmitted and non-transmitted alleles in nuclear families for all four investigated polymorphisms. In addition, the distributions of genotypes and alleles for the four polymorphisms did not differ significantly between our children and 200 healthy control patients. The allele frequencies of all polymorphisms were concordant with those observed in some other Caucasian populations. Conclusion: We found no association between the investigated gene variants and EH, so we conclude that they do not confer a significantly increased risk of the development of EH in the Slovenian population of hypertensive children.

Early renal insufficiency in a neonate with de novo partial trisomy of chromosome 10q.

Partial trisomy of the long arm of chromosome 10 is a well‐defined but rare syndrome. Clinical features of this chromosomopathy are a distinctive dysmorphic appearance, developmental delay, growth retardation, and in some cases, abnormalities of the extremities and renal, cardiac and ocular anomalies. This report describes a neonate with symmetric growth retardation and multiple dysmorphic features, in whom chromosomal analysis revealed a partial trisomy of chromosome 10q with a monosomy of the 13q34 region. The phenotype shares many common features with previously published cases. In addition to the typical features, our case also shows renal hypoplasia with early renal insufficiency and some genital anomalies.

A case of Shwachman-Diamond syndrome in a male neonate: Correspondence sections

Sir, We report a case of a male neonate presenting with clinical features of Shwachman-Diamond syndrome (SDS) in whom the IVS2DS T /C mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene has been identified. SDS is a rare, autosomal, recessive, multisystemic disorder, mainly characterized by growth retardation, exocrine pancreatic insufficiency and bone marrow dysfunction [1]. It was initially shown that SDS maps to the centromeric region of chromosome 7 [2]. In 2003, the SBDS gene and its pseudogene, SBDSP, were identified in the disease-associated interval at 7q11, and causative mutations in this gene were found in 89% of affected individuals [3]. The precise function of the SBDS protein in normal cells is still unknown. It has been hypothesized that it is involved in an aspect of RNA metabolism that is essential for the development of the exocrine pancreas, haematopoiesis and chondrogenesis [3]. The disease is highly heterogeneous [4], and no genotype phenotype correlations have been observed [5]. A male neonate was born as the second child to healthy, young, unrelated parents. Labour was induced at 36 wk gestation because of intrauterine growth retardation and the suspicion of a skeletal dysplasia. During pregnancy, amniocentesis was performed, which revealed a normal karyotype. Birthweight was 1940 g (60 g below the 3rd percentile for premature infants), birth length 37 cm (7 cm below the 3rd percentile for premature infants), head circumference 32 cm (3rd percentile) and Apgar score was 6/7. After birth, respiratory distress due to dysmaturity developed, necessitating respiratory support. Short extremities, a narrow thorax, hepatomegaly, generalized muscular hypotonia, and a distinctive paleness of the skin and mucous membranes were observed. There were no dysmorphic features. Laboratory studies revealed anaemia (haemoglobin 67 g/l), neutropenia (white blood cells 11.3 /10/l with 454/mm neutrophils) and thrombocytopenia (platelets 23 /10/l). The bone marrow was hypoplastic. Exocrine pancreatic insufficiency was diagnosed because of the high faecal fat content, decreased, practically undetected faecal chymothrypsin, and low serum and urinary amylase (serum amylase 0.1 mkat/l). Liver function tests and clotting studies were normal, as was the chloride sweat test. Congenital infections (cytomegalovirus, herpes simplex virus, Epstein-Barr virus, parvovirus B19) were also excluded, as were some metabolic disorders. Chest X-rays showed a cone-shaped thorax with horizontally placed irregular ribs. Metaphyseal changes in the distal radius and ulna and proximal femur were also noticed. The distal phalanx of the fifth toe and the middle phalanges of the third, fourth and fifth toes were undeveloped. Spinal X-ray was normal. No major osteopenia was observed. Abdominal ultrasound revealed a liver of normal size and structure, a hypoplastic pancreas and asplenia. The latter was confirmed scintigraphically. Ultrasound of the brain suggested agenesis of the corpus callosum, which was confirmed by brain CT scan. After birth the patient suffered from common septic conditions caused by Gram-negative organisms. The patient failed to thrive, despite pancreatic enzyme supplementation, with a weight gain of only 70 g in the first 2 mo of life. The patient died at the age of two and a half months from sepsis with refractory pancytopenia. Cytogenetic analysis of the patient showed a normal karyotype. The patient was also tested for possible subtelomeric rearrangements. FISH analysis, using the multiprobe T-system (Cytocell), showed all subtelomeric regions to be normal. Afterwards, molecular genetic analysis for achondroplasia mutations G380R and G375C in the fibroblast growth-factor receptor type 3 (FGFR3) gene was performed. He and his family members (brother, parents) were also tested for the presence of mutations 183 184 TA /CT and IVS2DS T /C in the SBDS gene. The detection of mutations G380 and G375C in the FGFR3 gave negative results. On the other hand, we detected the mutation IVS2DS T /C in the proband as well as in his mother and his unaffected brother. Because we did not observe two mutations in the SBDS gene, we could not completely confirm the diagnosis of SDS, which is an autosomal recessive condition. Therefore, we sequenced the 352-bp fragment from the proband using a dideoxy-cycle sequencing method. The mutation IVS2DS T /C was confirmed, but no other sequence variation was observed. Recent genetic studies have shown that mutations of the SBDS genes are present in the majority of patients with SDS. Most patients have compound heterozygous mutations of SBDS, consistent with a loss-of-function mechanism [6]. Boocock et al. [3] found mutations resulting from gene conversion in 89% of SDS patients, with 60% carrying two converted alleles and the rest only one converted allele. There is a subgroup of patients in whom SBDS mutations have not been found, suggesting that SDS is a genetically heteroge-

Polymorphisms in four candidate genes in young patients with essential hypertension: Some genetic factors in young hypertensives

Aim: To determine whether four potential genetic factors (polymorphisms in genes for alpha‐adducin, beta‐adducin, the G‐protein beta‐3 subunit and nitric oxide synthase) are important for the development of essential hypertension (EH) in Slovenian children and young adults with EH. Methods: Both a nuclear families approach and case‐control study have been performed. Genotyping of common polymorphisms in these genes using polymerase chain reaction was carried out in 104 nuclear families (an affected child, both parents) and in 200 control patients. Results: Using the transmission disequilibrium test, no statistically significant differences were found between the frequencies of transmitted and non‐transmitted alleles in nuclear families for all four investigated polymorphisms. In addition, the distributions of genotypes and alleles for the four polymorphisms did not differ significantly between our children and 200 healthy control patients. The allele frequencies of all polymorphisms were concordant with those observed in some other Caucasian populations.