Differences in the clinical spectrum of two adolescent male patients with Alström syndrome.

Alström syndrome is a rare disorder typified by early childhood obesity, neurosensory deficits, cardiomyopathy, progressive renal and hepatic dysfunction, and endocrinological features such as severe insulin resistance, type 2 diabetes, hyperlipidemia, and hypogonadism. Widespread fibrosis leads to multiple organ failure. Mutations in ALMS1 cause Alström syndrome. Two age-matched, unrelated adolescent males of Serbian descent with Alström syndrome underwent an extensive workup of blood chemistries, and ophthalmological, audiological, and genetic evaluations. Although both showed typical features of Alström syndrome in childhood, several differences were observed that have not been reported previously. Patient 1 was first studied at the age of 13 years for multisystemic disease and re-evaluated at the age of 15.5 years. Patient 2 is a 15-year-old boy who presented at birth with epilepsy and psychomotor developmental delay and generalized tonic-clonic seizures with severe cognitive impairment, features not documented previously in this syndrome. Sequencing analysis indicated two novel ALMS1 mutations in exon 8: p.E1055GfsX4 and p.T1386NfsX15. Metabolic and physiological similarities were observed in both patients, including severe insulin resistance, and truncal obesity with fat loss suggestive of partial lipodystrophy, supporting evidence for a role for ALMS1 in adipose tissue function. The unusual phenotypes of clonic-tonic seizures and severe cognitive abnormalities and lipodystrophy-like adiposity pattern have not been documented previously in Alström syndrome and may be an under-reported abnormality.

[Levosimendan treatment of severe acute congestive heart failure refractory to dobutamine/milrinone in children].

INTRODUCTION: Levosimendan is a novel positive inotropic agent which, improves myocardial contractility through its calcium-sensitizing action, without causing an increase in myocardial oxygen demand. Also, by opening ATP-sensitive potassium channels, it causes vasodilatation with the reduction in both afterload and preload. Because of the long half-life, its effects last for up 7 to 9 days after 24-hour infusion. CASE REPORT: We presented three patients 2, 15 and 17 years old. All the patients had severe acute deterioration of the previously diagnosed chronic heart failure (dilatative cardiomyopathy; univentricular heart with bidirectional Glenn anastomosis and restrictive bulboventricular foramen; bacterial endocarditis on artificial aortic valve with severe stenosis and regurgitation). Signs and symptoms of severe heart failure, cardiomegaly (cardio-thoracic index 0.65) and left ventricular dilatation (end-diastolic diameter z-score 2.6; 4.1 and 4.0) were confirmed on admission. Also, myocardial contractility was poor with ejection fraction (EF - 27%, 25%, 35%), fractional shortening (FS - 13%, 11%, 15%) and stroke volume (SV - 40, 60, 72 mL/m2). The treatment with standard intravenous inotropic agents resulted in no improvement but in clinical deterioration. Thus, standard intravenous inotropic support was stopped and levosimendan treatment was introduced. All the patients received a continuous 24-h infusion 0.1 microg/kg/min of levosimendan. In a single patient an initial loading dose of 11 microg/kg over 10 min was administrated, too. Levosimendan treatment resulted in both clinical and echocardiography improvement with the improved EF (42%, 34%, 44%), FS (21%, 16%, 22%) and SV (59, 82, 93 mL/m2). Hemodynamic improvement was registered too, with the reduction in heart rate in all the treated patients from 134-138 bpm before, to less than 120 bpm after the treatment. These parameters were followed by the normalization of lactate levels. Nevertheless, left ventricular end-diastolic diameter did not change after the levosimendan treatment. CONCLUSION: Our initial experience demonstrates that administration of levosimendan in patients with severe chronic heart failure not responsive to standard intravenous inotropic treatment might result in a significant clinical and hemodynamic improvement and that, in selected patients, it might be life saving. According to our best knowledge patients presented are the first pediatric patients treated with levosimendan in our country.

[Adams-Oliver syndrome: case report].

INTRODUCTION: Adams-Oliver syndrome is characterized by congenital aplasia of the vertex skin of the skull in combination with skull and transverse limb defects. CASE OUTLINE: We presented a 5-month old female infant with Adams-Oliver syndrome manifested as cutis marmorata, dilated scalp veins and limb reduction defects. Clinical manifestation also included thumb hypoplasia and extreme hypoplasia of other fingers, with agenesis of all toes on both feet. Echocardiogram revealed foramen ovale apertum. Venography showed dilated malformed scalp and neck veins, predominantly on the right side. On the basis of the clinical features and extended investigation we confirmed Adams-Oliver syndrome in the presented patient. CONCLUSION: We recommended prenatal diagnosis in case of future pregnancies, ultrasound examination, and follow-up of foetal anomalies.

[Stenting aortic coarctation in children: immediate and mid-term results].

INTRODUCTION: Stent implantation, in patients with different forms of aortic coarctation, has significant theoretical advantages over primary balloon dilatation (BD). It can achieve over-dilatation of the coarcted segment with the rigid endoprothesis maintaining the increase in vessel diameter regardless of the intimal injury and, thus, reducing the likelihood of restenosis. Moreover, by preventing vascular recoil, stents can successfully expand long-segment tubular coarctations, hypoplastic isthmus and hypoplastic transverse aortic arch. Finally, by facilitating good apposition of the torn intima to the aortic wall, they can significantly reduce the incidence of aneurysm formation. OBJECTIVE: Evaluation of the immediate and mid-term results of stent implantation in patients with different forms of aortic coarctation. METHODS: Between February 2005 and March 2010 eleven stents were implanted in nine patients (two female and seven male) either with post surgical or post primary BD residual coarctation/recoarctation or with native aortic coarcatation. Mean age of our patients was 14 +/- 3 years (9.4-18.1 years) and mean body weight 54 +/- 18 kg (29-76 kg). RESULTS: Pressure gradient across the coarctation site was reduced from 24.9 +/- 12.4 mm Hg before to 3.9 +/- 5.0 mm Hg after stenting (p = 0.000). There were no complications. Mean followup was 2.0 +/- 1.5 years (range 0.1-5.2 years). In patients with localised aortic arch narrowing no restenosis or aneurysm formation was observed (residual pressure gradient 0-5 mm Hg). CONCLUSION: In properly selected children (body weight > 25 kg), adolescents and young adults stenting is the method of choice for patients with various forms of aortic arch obstruction.

An unusual presentation of cardiomyopathy in a patient with microcephaly-cardiomyopathy syndrome.

We report the case of a 15-year-old male patient with microcephaly, dilated cardiomyopathy, mental retardation, secondary hypopituitarism, and minor dysmorphic features: downward- slanting palpebral fissures, narrow palate, small and low-set ears, fifth finger clinodactyly, sandal gaps on both feet, and anal stenosis. He was admitted to the pediatric intensive care unit with signs of progressive cardiac failure. Lethal outcome occurred 25 days after admission. Most clinical features of the patient were similar to those of the four previously reported patients with microcephaly-dilated cardiomyopathy syndrome, but some of this patient's features, such as anal stenosis and secondary hypopituitarism, were unique.

Low-bandwidth teleconsultations for patients with complex congenital heart diseases.

We have reviewed our experience with a low-bandwidth paediatric telecardiology link (using ISDN at 128 kbit/s) between a tertiary centre in Belgrade and a tertiary centre in London. Over a two-year period, 12 videoconferences were held, during which 40 case histories of 38 patients were presented from Belgrade. The patients were aged 7 days to 20 years, and most of them had complex congenital heart defects. Changes in diagnosis and/or therapy occurred in 21 cases. Clinically relevant changes in diagnosis occurred in 2/40 cases (5%). In 12 cases, there were slight differences in opinion which resulted in minor changes in therapy for 9 of the patients. In another 9 patients, major changes in therapy occurred. There were no major problems with the quality of image and sound in any of the videoconferences. Our experience suggests that when there are experienced paediatric cardiologists at both ends of the connection, transmission via a single ISDN line is safe and accurate.

Age-related role of ambulatory electrocardiographic monitoring in risk stratification of patients with complete congenital atrioventricular block.

AIMS: The aim of the paper was to assess the importance of 24 h electrocardiographic Holter monitoring in determining predictive factors for Adams-Stokes (AS) attacks and heart failure (HF) in children and adolescents with complete congenital atrioventricular block (CCAVB). METHODS AND RESULTS: Forty-five patients were divided into two groups according to the presence of AS attacks and HF and six age-related subgroups. The following parameters of 24 h electrocardiographic Holter monitoring were analysed: (i) minimum heart rate (HR), (ii) maximum HR, (iii) average HR, (iv) daytime HR (v) rhythm and conduction disturbance. Adams-Stokes attacks and HF occurred in 10 and 8 patients, respectively (40%). Five of six neonates with HF had maximum HR < 74 bpm and daytime HR < 58 bpm. Maximum HR below 68 bpm and daytime HR below 52 bpm were recorded in all the children up to 8 years of age with AS attacks and HF and only in 3 of 14 asymptomatic patients. All the patients above 8 years of age with AS attacks had maximum HR below 62 bpm. Of 6 patients with daytime HR < 50 bpm AS attacks were present in two. Episodes of marked ventricular slowing during sleep were registered in 4 of 10 (40%) patients and in 3 of 27 (11%) symptomless patients. CONCLUSION: Risk factors for development of AS attacks and HF in patients with CCAVB include: (i) maximum HR < 74 bpm in neonates, <68 bpm up to the age of 8 and <62 bpm at ages above 8, (ii) daytime HR <58 bpm in neonates and < 52 bpm till the age of 8, and (iiii) abrupt pauses in ventricular rate that are at least twice the basic cycle length after the neonatal period.