Relation between biomarkers and clinical severity in patients with Smith–Lemli–Opitz syndrome

Smith–Lemli–Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n?=?4, clinical score <20) was 0.5–18 years, cholesterol was 2.37?±?0.8 mmol/L, and 7DHC was 0.38?±?0.14 mmol/L. In the group of typical SLOS (n?=?7, score 20–50), the diagnosis was set up earlier (age of 0.1–7 years); t-cholesterol was 1.47?±?0.7 mmol/L, and 7DHC was 0.53?±?0.20 mmol/L. Patients with severe SLOS (n?=?4, clinical score?>?50) died as newborns and had the lowest t-cholesterol (0.66?±?0.27 mmol/L), and 7DHC was 0.47?±?0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p?=?0.01), and between the Cho/7DHC ratios of groups (p?=?0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p?=?0.003) and mild SLOS (p?=?0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n?=?10) combined with statin therapy (n?=?9), increase of aspartate aminotransferase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. Conclusion: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.     

A patient with Smith–Lemli–Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement

Background  

The Smith–Lemli–Opitz (SLO) syndrome is a multiple congenital anomaly with mental retardation due to a decreased or lack of activity of 7-dehydrocholesterol reductase as a consequence of mutations of the DHCR7 gene. This paper describes a special patient with SLO syndrome. Laboratory examination showed low cholesterol (2.77 mmol/L) and increased 7-dehydrocholesterol level (102 mg/L). Molecular genetic analysis revealed a compound heterozygosity c.964-1G>C/p.G366V (c.G1370T) of the proband. The p.G366V is a novel mutation of the DHCR7 gene with guanine by thymine nucleotide exchange resulting in glycin by valin amino acid exchange in the dehydrocholesterol reductase enzyme. Simvastatin (0.2 mg/kg/day) and cholesterol replacement therapy (150–250 mg/kg/day) led to significant improvement in the patient's laboratory findings (7-dehydrocholesterol, cholesterol) as well as in his behavior and gross motor function.     

Expanding the phenotype of alopecia–contractures–dwarfism mental retardation syndrome (ACD syndrome): description of an additional case and review of the literature

Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.     

A prospective study of the presentation and management of dancing eye syndrome/opsoclonus–myoclonus syndrome in the United Kingdom

The incidence, mode of presentation and management of Dancing Eye Syndrome/Opsoclonus–Myoclonus Syndrome (DES/OMS) was prospectively evaluated in 20 United Kingdom (UK) paediatric neurology centres by questionnaire over a 24-month period between 2003 and 2005.Nineteen children were notified, giving an incidence of 0.18 cases per million total population per year. Mean age at presentation was 18 months (range 3–42 months). Fifteen families consented to participate in the study. Atypical features were present in 6/15 cases including very delayed presentation of opsoclonus, dysphagia, and rapid spontaneous improvement without treatment.Only 4/15 cases were associated with neuroblastoma (NB) but current practice in excluding this is diverse and a standardised approach is suggested.     

Surgical treatment of childhood hepatoblastoma in the Netherlands (1990–2013)

Background

Achievement of complete surgical resection plays a key role in the successful treatment of children with hepatoblastoma. The aim of this study is to assess the surgical outcomes after partial liver resections for hepatoblastoma, focusing on postoperative complications, resection margins, 30-day mortality, and long-term survival.

Method

Chart reviews were carried out on all patients treated for hepatoblastoma in the Netherlands between 1990 and 2013.

Results

A total of 103 patients were included, of whom 94 underwent surgery. Partial hepatectomy was performed in 76 patients and 18 patients received a liver transplant as a primary procedure. In 42 of 73 (58 %) patients, one or more complications were reported. In 3 patients, information regarding complications was not available. Hemorrhage necessitating blood transfusion occurred in 33 (45 %) patients and 9 (12 %) patients developed biliary complications, of whom 8 needed one or more additional surgical interventions. Overall, 5-year disease-specific survival was 82, 92 % in the group of patients who underwent partial hepatectomy, and 77 % in the group of patients who underwent liver transplantation.

Conclusions

Partial hepatectomy after chemotherapy in children with hepatoblastoma offers good chances of survival. This type of major surgery is associated with a high rate of surgical complications (58 %), which is not detrimental to survival.

     

Hybrid Transcatheter–Surgical Palliation

The outcome of patients with hypoplastic left heart (HLH) is determined by many factors, particularly by the first-step palliative procedure in newborns undergoing the Norwood procedure, its Sano modification, or, rarely, through challenging biventricular repairs. Duct stenting combined with bilateral pulmonary artery banding (PAB) is a new method employed as an alternative first-step approach in a number of centers worldwide. We describe this interventional–surgical “hybrid approach” as an additional strategy for the treatment of newborns with HLH syndrome and HLH complex. Between 1998 and April, 2006, 58 newborns underwent ductal stenting and bilateral PAB. These patients underwent surgical bilateral PAB initially, followed by percutaneous duct stenting; the only exception to this were patients in whom duct stenting was performed as a rescue procedure. Various balloon-expandable and self-expandable stents with different widths and lengths were used during the 8-year period of this study. Balloon dilatation of the atrial septum was performed when indicated. This included 5 patients in whom the atrial septum was stented. Aortic arch reconstruction (AAR) combined with a bidirectional cavopulmonary connection (BCPC) was performed at a median age of 4.8 months (range, 2.6–7.5), and total cavopulmonary connection (TCPC) was performed at a median age of 3.1 years (range, 2.5–4). Nine patients were listed for heart transplantation (HTX) and transplanted with AAR when a donor heart was available. Depending on growth of left ventricular structures, biventricular repair (BVR) was performed at a median age of 7.1 months (range, 3.5–10). Overall, 8 of 58 patients (13.8%) treated by the transcatheter–surgical hybrid approach died during the study period. The mortality rate for duct stenting was 1.7% (l/58), and it was 1.7% for bilateral PAB as well. Twenty-seven patients received an AAR/BCPC; 2 of them died (7.4%). Additionally, 1 of 2 patients with AAR/BCPC died while on the waiting list for HTX, resulting in a total mortality rate of 11% with an actuarial survival rate of 89%. One patient is still awaiting AAR + BCPC. Three patients died while on the waiting list for HTX despite successful bilateral PAB and duct stenting. The 30-day mortality rate for TCPC (n = 11), HTX (n = 8), and 18 patients with BVR was 0. The actuarial survival rate for patients with BVR is 93%. Postnatal transcatheter–surgical hybrid palliation expands the surgical options for newborns with HLH. Using hybrid palliation, Norwood stage I operation can be avoided in the neonatal period, the waiting period for children scheduled for cardiac transplantation can be extended, and observation for left ventricular growth suitable for biventricular repair as well.     

Sturge–Weber syndrome: From the past to the present

Sturge–Weber syndrome is a rare sporadic neurocutaneous syndrome the hallmark of which is a facial port-wine stain involving the first division of the trigeminal nerve, ipsilateral leptomeningeal angiomata and angioma involving the ipsilateral eye. Our understanding of the disease process has vastly improved since it was first described in 1879, with recent identification of an activating somatic mutation in the GNAQ gene found in association with both Sturge–Weber syndrome and non-syndromic facial port-wine stain. Sturge–Weber syndrome is marked by a variable but usually progressive course in early childhood characterised by seizures, stroke-like episodes, headaches, neurological and cognitive deterioration, hemiparesis, glaucoma and visual field defects. More recently, the increased prevalance of otolaryngological, endocrine and emotional–behavioural issues have been established. Neurophysiology and neuroimaging studies provide information regarding the evolution of changes in Sturge–Weber syndrome over time. Early recognition and aggressive management of symptoms remains cornerstone in the management of this syndrome. An international collaborative effort is needed to maximise our understanding of the natural history and response to interventions in Sturge–Weber Syndrome.     

Management of symptomatic Wolff–Parkinson–White syndrome in childhood

The term “ventricular preexcitation” or “preexcitation” refers to the presence of a delta wave and short PR interval on electrocardiogram (ECG) during normal sinus rhythm. The Wolff–Parkinson–White (WPW) syndrome refers to preexcitation during sinus rhythm, in association with episodes of supraventricular tachycardia (SVT). The delta wave represents extra-nodal conduction via an accessory connection located along the atrioventricular groove or the septal region, and this substrate can support atrioventricular reentrant tachycardia. Patients with Wolff–Parkinson–White syndrome may experience symptoms of palpitations, dizziness, syncope, or sudden cardiac arrest related to supraventricular tachycardia; infants may present with congestive heart failure. Catastrophic symptoms such as cardiac arrest or sudden death may be triggered from atrial fibrillation with rapid antegrade conduction to the ventricle via the accessory connection, resulting in ventricular fibrillation [1], [2], [3], [4]; this risk is likely higher in patients in the first three decades of life [4], [5]. Sudden cardiac arrest as the initial symptom may be more common in younger patients [2], [4], [6]; for this reason, appropriate evaluation and management of the young patient with preexcitation is essential.     

Surgical care of the pediatric Crohn’s disease patient

Despite the significant advances in the medical management of inflammatory bowel disease over the last decade, surgery continues to play a major role in the management of pediatric Crohn’s disease (CD). While adult and pediatric Crohn’s disease may share many clinical characteristics, pediatric Crohn’s patients often have a more aggressive phenotype, and the operative care given by the pediatric surgeon to the newly diagnosed Crohn’s patient is very different in nature to the surgical needs of adult patients after decades of disease progression. Children also have the unique surgical indication of growth failure to consider in the overall clinical decision making. While surgery is never curative in CD, it has the ability to transform the disease process in children, and appropriately timed operations may have tremendous impact on a child’s physical and mental maturation. This monograph aims to address the surgical care of Crohn’s disease in general, with a specific emphasis on the surgical treatment of small intestinal and ileocecal involvement.     

Surgical Placement of Totally Implantable Venous Access Device–An Institutional Experience

Objectives

To investigate the advantages and disadvantages of Totally implantable venous access devices (TIVAD) catheter in pediatric age group and also to review this subject in the recent literature and compare the results with the present results.

Methods

A total of 61 cases, 2 mo to 14 y old, were included in the index study. TIVADs were implanted in these patients for chemotherapy. The device was inserted under general anesthesia (GA) by open technique. All the children were followed up for a mean period of 7.2 mo.

Results

Out of 61 cases, 9 cases had complications; 3 requiring removal of the port due to infection and in one case the device had to be reinserted due to malpositioning, one had late wound dehiscence with exposed port chamber which needed operative correction and four had minor wound infections. There was no mortality. Complications like hemo or pneumothorax, arterial puncture, hematoma formation were very less with open technique of insertion of the port. Most patients and their parents were satisfied with TIVAD.

Conclusions

Thus, TIVAD can be a useful device for many chronic patients who need an IV access for multiple injections especially in pediatric age group.     

Gómez–López-Hernández syndrome: reappraisal of the diagnostic criteria

Gómez–López-Hernández syndrome (GLHS) is a rare and possibly underdiagnosed condition. So far, 21 patients have been reported and all of them were sporadic observations. We report six additional patients. The hallmark triad of GLHS, also named cerebellotrigeminal dermal dysplasia, consists of rhombencephalosynapsis, trigeminal anesthesia (often giving rise to corneal opacities), and bilateral parietal or parieto-occipital alopecia. Our patients had rhombencephalosynapsis and alopecia, but none had trigeminal dysfunction. In this respect, the term cerebellotrigeminal dermal dysplasia is potentially misleading. In conclusion, only rhombencephalosynapsis and alopecia are consistently present in GLHS and are required diagnostic criteria, while trigeminal anesthesia, dysmorphic features, and ataxia are inconsistent findings. A high index of suspicion is required to diagnose GLHS, particularly as alopecia tends to be hidden by surrounding scalp hair.     

Possible association of Down syndrome and exstrophy–epispadias complex: report of two new cases and review of the literature

In the past, several midline defects have been associated with Down syndrome (DS) on a regular basis, e.g. heart defects, cleft lip and palate, neural tube defects, omphalocele and anal atresia. The exstrophy–epispadias complex (EEC) represents a rare midline defect, rarely described in association with DS. Here, we report on the co-occurrence of DS and EEC in two, so far, unreported cases and present a review of the literature. We suggest that EEC represents a rare but inherent part in the spectrum of DS-associated midline defects.     

Dyssynchronous ventricular contraction in Wolff–Parkinson–White syndrome: a risk factor for the development of dilated cardiomyopathy

Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff–Parkinson–White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n?=?2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. Conclusions: A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.