Ercan Tutar

Familial neonatal Marfan syndrome due to parental mosaicism of a missense mutation in the FBN1 gene

We present a family in which three siblings were born with neonatal Marfan syndrome (MFS) to unaffected parents. The clinical findings included joint contractures, large ears, loose skin, ectopia lentis, muscular hypoplasia, aortic root dilatation, mitral and tricuspid valve insufficiency, and pulmonary emphysema. All three siblings died due to cardiorespiratory insufficiency by 2–4 months of age. Screening of the FBN1 gene showed the heterozygous c.3257G > A (p.Cys1086Tyr) mutation in the proband. Mosaicism of the mutation was demonstrated in the somatic cells and in the germ line of the father. Although three examples of parental mosaicism for classical MFS were demonstrated previously, this is the first report of familial occurrence of neonatal MFS due to a heterozygous mutation in FBN1. In conclusion, the p.Cys1086Tyr mutation in FBN1 is consistently associated with neonatal MFS. Parental mosaicism should always be kept in mind when counseling families with MFS.

The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

Myocardial Tissue Velocities in Neonates

Background: Tissue Doppler echocardiography (TDE) has been applied to the children age group; however, myocardial tissue velocities of neonates have been reported by few researchers. Methods: Myocardial velocities along the longitudinal axis of the left ventricle were measured in two groups: 50 term neonates within 5 days after birth and 54 healthy children by TDE. Sample volumes were placed in mitral lateral annulus (MLA), mitral medial annulus (MMA), and in the basal and middle parts of the left ventricular lateral wall (LVLW) and interventricular septum (IVS). Results: The highest myocardial velocities were obtained from MLA. In all segments, the mean systolic velocity (Sw) was found significantly lower than the mean early diastolic (Ew) and atrial systolic velocities (Aw) (P < 0.0001). The mean Aw was the dominant component in the MMA and were significantly higher than Ew (P < 0.001). The mean Ew/Aw in the MMA and MLA increased significantly while replacing the Doppler beam from base to apex. TDE indexes of neonates, except Aw obtained from MLA and MMA, were significantly lower than that of children group (P < 0.0001 and P < 0.0001, respectively). The mean E/Ew ratio of the left ventricle in neonates was found to be significantly higher than that found in children group (P < 0.0001). Conclusion: In neonates, the diastolic and systolic myocardial velocities of the left ventricle were significantly lower than those measured in the children group. Decreased myocardial tissue values of neonates might be reflecting the immaturity of neonatal myocardium.

Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiency.

Aim: To analyse the activity of the autonomic nervous system during breath‐holding spells, we assessed the ECG changes, including ventricular repolarization parameters before and during the spell. We also analysed the effects of iron deficiency on these ECG parameters. Methods: The study group consisted of 37 children with breath‐holding spells (30 cyanotic, 7 pallid) (mean age±SD: 12.9±10.8 mo). Twenty‐six healthy children (mean age±SD: 14.4±8.6 mo) served as a control group. All patients and controls had standard 12‐lead simultaneous surface ECG. All patients had ECG recordings during at least one severe breath‐holding spell obtained by “event recorder”. Traces obtained by “event recorder” were analysed in terms of mean heart rate and the frequency and duration of asystole during the spell. Results: Respiratory sinus arrhythmia on standard ECGs and asystole frequency during spells were higher in patients with pallid breath‐holding spells. Patients with iron deficiency had a lower frequency of respiratory sinus arrhythmia and prolonged asystole time during the spell. There was no difference in terms of ventricular repolarization parameters (QT/QTc intervals and QT/QTc dispersions) between patients and controls and between patient subgroups (cyanotic versus pallid).

Clinical and Epidemiological Characteristics of Children with Kawasaki Disease in Turkey

BACKGROUND Kawasaki disease (KD) is the leading cause of acquired heart disease in childhood in the developed countries. The objective of this study is to describe the clinical and epidemiological characteristics of children with KD in Turkey. METHODS The medical records of 24 patients treated for KD between January 1994 and June 2009 at Ankara University Medical School, Turkey were reviewed. RESULTS The male-to-female ratio was 1.4 : 1. The median age at diagnosis was 2 years (range: 6.5 months to 11 years). Conjunctivitis and changes in the lips and oral cavity were seen in 21/24 (87.5%), cervical lymphadenopathy 17/24 (70.8%), polymorphous rash 16/24 (66.7%) and peripheral changes in 12/24 (50%). Coronary artery abnormality (CAA) was observed in 8/24 (33.3%) cases. CAA was seen in both the complete and incomplete groups with similar frequency (31.3% vs. 37.5%, respectively). CONCLUSIONS KD must be kept in mind in the differential diagnosis of infants with prolonged fever.

The Effect of p.Arg25Cys Alteration in NKX2-5 on Conotruncal Heart Anomalies: Mutation or Polymorphism?

Heterozygous mutations in the NKX2-5 gene of patients with various congenital heart defects have been reported. Most of the congenital heart defects associated with the mutations in the NKX2-5 gene are conotruncal heart anomalies, primarily the tetralogy of Fallot. In this study, the authors screened 72 Turkish children with conotruncal heart anomalies and 185 healthy control subjects to find the NKX2-5 alterations. They found one previously documented NKX2-5 missense alteration, heterozygous c.73C>T (p.Arg25Cys), in a 10-year-old boy with tetralogy of Fallot. The same heterozygous alteration was found also in the patient’s healthy father and in two unrelated persons in the healthy control group. The current study shows for the first time the presence of p.Arg25Cys in healthy control subjects other than African Americans. These results show that no genetic support exists for the pathogenecity of this alteration, although a previous in vitro study and theoretical predictions suggest a structural/functional difference in the altered protein region.

Antistreptococcal Response is Exaggerated in Children with Familial Mediterranean Fever

Abstract: Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Although the pathogenesis of the disease is not yet completely understood, enhanced acute-phase responsiveness is considered to be one of the most important mechanisms. The presence of high levels of antistreptolysin O (ASO) antibodies and streptococcus-associated diseases, such as acute poststreptococcal glomerulonephritis (AGN) and acute rheumatic fever (ARF), has been reported in patients with FMF. In order to better understand the effect of FMF on antistreptococcal antibody response, we measured ASO and antideoxyribonuclease B (anti-DNAse B) levels in patients with FMF and compared them with those in healthy controls. The study consisted of two parts. In the first step, antistreptococcal antibody levels were analysed in 44 patients with FMF and 165 healthy children who had no history or clinical evidence of upper respiratory tract infection (URTI) for the last 4 months. In the second step, antistreptococcal antibody levels were measured in 15 patients with FMF and 22 healthy controls in response to documented group A β-haemolytic streptococcal pharyngitis. In the first part of the study, ASO and anti-DNAse B levels in patients with FMF were found to be significantly higher than those in healthy controls (P<0.001). In the second part, ASO and anti-DNAse B titres were found to be significantly higher in patients with FMF than in controls (P<0.001 and <0.05, respectively) 4 weeks after a positive throat culture. We concluded that patients with FMF have an exaggerated response to streptococcal antigens and might be prone to poststreptococcal non-suppurative complications, such as ARF.

Global left-ventricular function by tissue Doppler imaging in pediatric dialysis patients

Cardiovascular abnormalities are observed in most children with end-stage renal disease (ESRD). The aim of this study was evaluation of left-ventricular (LV) myocardial performance using tissue-Doppler imaging (TDI) in patients with ESRD. Twenty-five patients with ESRD and 25 healthy gender- and age-matched control subjects were assessed with conventional M-mode echocardiography, pulsed-wave Doppler (PWD), and TDI. Myocardial Performance Index (MPI) and LV mass index (LVMI) were calculated. MPI and conventional echo-Doppler indices were compared in the ESRD and control groups. Significant differences were present in the mean systolic and diastolic blood pressure (BP) between children with ESRD and healthy children (p = 0.007 and p < 0.001, respectively). The mean LVMI was significantly greater in the patient group (p < 0.001). The tissue-Doppler MPI of patients was significantly higher than that in healthy children (p < 0.001). LVMI was significantly correlated with systolic and diastolic BP. MPI obtained by TDI was significantly correlated with LVMI. Our study confirms that LV dysfunction is present in patients with ESRD and hypertension is an important risk factor.

Ophthalmo‐acromelic syndrome: Report and review

The ophthalmo-acromelic syndrome of Waardenburg is an autosomal recessive trait comprising eye malformations ranging from true anophthalmia to mild microphthalmia with acromelic malformations. Some 29 affected individuals have been reported since Waardenburgs first report in 1935 [Waardenburg et al., 1961]. We report on a new case with bilateral anophthalmia and typical limb malformations. The patient also was found to have interruption of the inferior vena cava with azygos continuation as an additional finding. The previous reports are reviewed to elucidate the spectrum of the syndrome.

Incidence of pericardial effusion during attacks of familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disorder that affects primarily Jews, Armenians, Turks, and Arabs. It is characterised by recurrent, self limited attacks of fever accompanied by inflammation of the peritoneal, synovial, and pleural surfaces.1 Pericardial involvement is a well known (0.7–1.4%) but rare feature of the disease.2,3 Our initial observation of two patients who had recurrent pericarditis as a sole manifestation of FMF4 has led us to suggest that pericardial inflammation is more prevalent than generally believed. Since echocardiography is a non-invasive and sensitive tool for the detection of pericardial effusion, we undertook an echocardiographic study to assess the exact frequency of pericardial effusions during attacks of FMF. Two dimensional, M mode, and Doppler echocardiographic examinations were performed during 55 consecutive FMF attacks in 42 patients (15 female, 17 male). Echocardiographic study was carried out by one of the authors (ET or SA) and reviewed by the other one, who was aware of the diagnosis of FMF but unaware of the presence or absence of chest pain. Typical attacks of FMF consisted of fever and serositis including peritoneum, synovium, and pleura lasting 1–4 days. Attacks of FMF were recurrent and self limited. FMF was diagnosed according to established clinical criteria or molecular analysis when appropriate (in 37 patients).1 None of the patients had …