Adducted thumbs: a clinical clue to genetic diagnosis.

Adducted thumbs are an uncommon congenital malformation. It can be an important clinical clue in genetic syndromes, e.g. the L1 syndrome. A retrospective survey was performed including patients with adducted thumbs referred to the Department of Clinical Genetics between 1985 and 2011 by perinatologists, (child) neurologists or paediatricians, in order to evaluate current knowledge on the genetic etiology of adducted thumbs. Twenty-five patients were included in this survey. Additional features were observed in 88% (22/25). In 25% (4/16) of the patients with adducted thumbs and congenital hydrocephalus L1CAM gene mutations were identified. One patient had a mosaic 5p13 duplication. Recommendations are made concerning the evaluation and genetic workup of patients with adducted thumbs.

Implementation of a mobile 0.15-T intraoperative MR system in pediatric neuro-oncological surgery: feasibility and correlation with early postoperative high-field strength MRI.

INTRODUCTION: We analyze our preliminary experience using the PoleStar N20 mobile intraoperative MR (iMR) system as an adjunct for pediatric brain tumor resection. METHODS: We analyzed 11 resections in nine children between 1 month and 17 years old. After resection, we acquired iMR scans to detect residual tumor and update neuronavigation. We compared final iMR interpretation by the neurosurgeon with early postoperative MR interpretation by a neuroradiologist. RESULTS: Patient positioning was straightforward, and image quality (T1 7-min 4-mm sequences) sufficient in all cases. In five cases, contrast enhancement suspect for residual tumor was noted on initial postresection iMR images. In one case, a slight discrepancy with postoperative imaging after 3 months was no longer visible after 1 year. No serious perioperative adverse events related to the PoleStar N20 were encountered, except for transient shoulder pain in two. CONCLUSIONS: Using the PoleStar N20 iMR system is technically feasible and safe for both supra- and infratentorial tumor resections in children of all ages. Their small head and shoulders favor positioning in the magnet bore and allow the field of view to cover more than the area of primary interest, e.g., the ventricles in an infratentorial case. Standard surgical equipment may be used without significant limitations. In this series, the use of iMR leads to an increased extent of tumor resection in 45 % of cases. Correlation between iMR and early postoperative MR is excellent, provided image quality is optimal and interpretation is carefully done by someone sufficiently familiar with the system.

Congenital hydrocephalus in clinical practice: a genetic diagnostic approach.

Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Clinical Genetics between 1985 and 2010 by perinatologists, (child) neurologists or pediatricians. Patients with hydrocephalus secondary to other pathology were excluded from this survey. We classified patients with primary congenital hydrocephalus into two main groups: non-syndromic hydrocephalus (NSH) and syndromic hydrocephalus (SH). Seventy-five individuals met the inclusion criteria, comprising 36% (27/75) NSH and 64% (48/75) SH. In 11% (8/75) hydrocephalus was familial. The cause of hydrocephalus was unknown in 81% (61/75), including all patients with NSH. The male-female ratio in this subgroup was 2.6:1, indicating an X-linked factor other than the L1CAM gene. In the group of SH patients, 29% (14/48) had a known cause of hydrocephalus including chromosomal abnormalities, L1 syndrome, Marden-Walker syndrome, Walker-Warburg syndrome and hemifacial microsomia. We performed this survey in order to evaluate current knowledge on the genetic etiology of primary congenital hydrocephalus and to identify new candidate genes or regulatory pathways for congenital hydrocephalus. Recommendations were made concerning the evaluation and genetic workup of patients with primary congenital hydrocephalus. We conclude that further molecular and functional analysis is needed to identify new genetic forms of congenital hydrocephalus.

Intraspinal dermoid and epidermoid tumors: report of 18 cases and reappraisal of the literature.

Intraspinal dermoid and epidermoid tumors are two histopathological subtypes of cutaneous inclusion tumors of the spine. This classification is based on obsolete embryological knowledge. In fact, according to current embryology, both tumor types consist of ectodermal derivatives. Therefore, we hypothesized that dermoid and epidermoid tumors do not differ in clinical practice. To explore this hypothesis, we studied the clinical, radiological and intraoperative findings of 18 patients, and related these findings to the histopathological characteristics of the tumor. No differences were found between dermoid and epidermoid tumors regarding clinical presentation, radiological examination and outcome, while intraoperative diagnosis by the surgeon correlated with the histopathological diagnosis in only 8 of 18 cases. Therefore, the histopathological difference between intraspinal dermoid and epidermoid tumors is not important in clinical practice and should be avoided. A new nomenclature is proposed in which both tumor types are referred to as 'spinal cutaneous inclusion tumors'.

The spinal dermal-sinus-like stalk.

OBJECTS: In this study, a disjunction anomaly mimicking the spinal congenital dermal sinus (DS) is described. This anomaly is referred to as the dermal-sinus-like stalk. Dissimilarities between a true dermal sinus and a dermal-sinus-like stalk are discussed. CLINICAL MATERIAL: Three cases in which a spinal congenital dermal sinus was suspected are presented. A similar anatomical configuration, different from that of a dermal sinus, was found. All cases presented with a skin-covered dimple from which a solid tract was seen continuing intramedullary in two cases and intraspinally in one case. None of the patients presented with signs of infection or an associated dermoid-epidermoid tumor. Clinical, radiological, and surgical findings are discussed. A hypothesis is made on the pathological genesis of this malformation. CONCLUSION: A dermal-sinus-like stalk is a malformation similar to a spinal congenital dermal sinus but is not associated with DS-related complications. Despite important clinical, radiological, surgical, and histopathological differences, it is difficult to distinguish this malformation from a true DS based on clinical and radiological examination alone. Therefore, surgical intervention, at the time of diagnosis, is recommended in all cases.

Analysis of the success and failure of endoscopic third ventriculostomy in infants less than 1 year of age.

OBJECTIVES: In infants less than 1 year of age, the value of endoscopic third ventriculostomy (ETV) is controversial. It is believed to cause more morbidity and to have higher failure rates. We analyzed our data enlarging the reported pool of ETV outcome in infants less than 1 year of age. MATERIALS AND METHODS: We performed 12 ETVs in ten patients younger than 1 year of age. All patients had predominant supratentorial hydrocephalus. We defined ETV success as a shunt-free follow-up of at least 12 months, however, allowing re-ETV. CONCLUSION: ETV should be considered as initial treatment and carries low morbidity in these infants. As the immune system rapidly matures, postponing shunt implantation for several months or even weeks would make an ETV procedure worthwhile. On the other hand, as success probability rapidly increases 4 months after birth, re-ETV should always be considered first.

Anatomy and surgery of the infected dermal sinus of the lower spine.

OBJECT: Cases of infected dermal sinus are scarce and detailed surgical anatomical descriptions are hardly found in literature. The clinical, radiological, and surgical findings in four cases of an infected dermal sinus located at the lower spine are presented to elucidate the pathological anatomical configuration. CLINICAL MATERIAL: The first case showed two dermal sinuses with a parallel course extra- and intradurally, ending in a confluence of cavities connected to the conus. In this case, as well as in the fourth case, the signs and symptoms were those of meningitis. The second case presented with meningitis and a subdural empyema, while the third case presented with an intradermoid-intramedullary abscess at the junction between the DS and the conus. This child probably showed signs and symptoms of conus involvement as early as during pregnancy. CONCLUSION: The anatomy of the nervous elements in this congenital anomaly is heavily disturbed, more particularly in case of infection, due to extensive arachnoidal scarring. The latter renders dissection laborious and recognition of anatomical details difficult, resulting in complete excision of a dermal sinus in less than half of the cases. Despite their variability in presentation, most cases of an infected dermal sinus show similar characteristic features.

De novo duplication (5)(q31.3q33.3): report of a patient and characterization of the duplicated region using microdissection and FISH.

We report on a 2-year-old boy presenting with growth and psychomotor retardation and facial anomalies, including a flat face with prominent forehead, a flat nasal bridge and flat occiput, unusually long curved eyelashes, and a thin upper lip with down-turned corners of the mouth. Analysis of GTG-banded chromosomes demonstrated that the patient had extra chromosomal material in the long arm of one chromosome 5. This chromosome aberration was characterized further using microdissection and FISH with band-specific probes and a de novo direct duplication (5)(q31.3q33.3) was shown to be present. We have compared this case with others known to be partially trisomic for chromosome 5q reported in the literature.

Helmet versus nonhelmet treatment in nonsynostotic positional posterior plagiocephaly.

A total of 105 infants with nonsynostotic posterior plagiocephaly were treated using a helmet or by head positioning. Effect of treatment was scored using a cosmetic outcome score (0-10 points) assigned by the parents. The onset of the observed skull deformity correction was not different for the helmet vs. nonhelmet treatment. Improvement was significantly better and faster in the helmet group compared with nonhelmet treatment (p < 0.01 and p < 0.001, respectively).

[Atenolol for preventing recurrence of atrioventricular reentry tachycardia in childhood]. / Atenolol zur Rezidivprophylaxe von atrioventrikulären Reentrytachykardien im Kindesalter.

BACKGROUND: Supraventricular reentrant tachycardias are the most common cardiac arrhythmia observed in infancy and childhood. The often benign clinical course of the disease warrants careful selection of any antiarrhythmic drug given to prevent recurrencies, in order to avoid potentially dangerous side-effects such as proarrhythmia. This study reports our experience with atenolol in the longterm treatment of infants and children with supraventricular tachycardias. PATIENTS AND METHODS: A search of our database was made and all the children admitted in our institution between 1987 and 1995 for treatment of supraventricular tachycardia were selected. Patients who had longterm oral treatment with atenolol were retrospectively evaluated and were seen during 1996 in our outpatient clinic for a follow-up examination including a Holter-monitor. RESULTS: 14 infants and children with a median age of 2 9/12 years at first presentation could be evaluated. In 10 patients, atenolol was the first antiarrhythmic drug given. In 10 of the patients (72%) therapy with atenolol was considered successful and no further attacks of tachycardia occurred. In 2 patients a partial response to atenolol was seen with an important decrease in the frequency of tachycardias. Two patients showed no effect of treatment and the betablocker was withdrawn. The effect of the drug on heart rate and blood pressure was mild and did not lead to symptoms. In no case had the drug to be withdrawn for adverse effects. After a mean follow-up of 50 months (3-105 months), 7 patients were off the drug and free of recurrencies while among the 5 children still on atenolol, only one experienced rare episodes of tachycardia. CONCLUSION: Atenolol is efficient in the longterm treatment of supraventricular tachycardias and due to its favorable risk profile can be recommended as first line treatment option.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

OBJECTIVES: To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). METHODS: The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. RESULTS: Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). CONCLUSIONS: The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed.

Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation.

Cardiac arrhythmias can present with the signs and symptoms of a seizure disorder. This potentially life-threatening underlying cause of non-febrile seizures should be recognized early, since successful specific treatment is possible. The purpose of this retrospective study was to examine common features in such patients. Over a period of 25 years, eight patients were initially treated for up to 5 years at our institution for a seizure disorder until dysrhythmia as the underlying cause of the seizures was disclosed. The main symptom was drop attacks coinciding with physical activity or emotional stress. Convulsions were only rarely observed. In five of the eight patients the underlying disorder was the long-QT-syndrome (Romano-Ward syndrome). In one patient intermittent complete atrioventricular block was found, another patient showed ventricular tachydysrhythmia of unknown etiology and the last patient suffered from hypertrophic cardiomyopathy.

[Therapeutic efficacy and diagnostic potential of adenosine in infants and children]. / Therapeutischer Nutzen und diagnostische Möglichkeiten von Adenosin bei Säuglingen und Kindern.

In an open study a total of 53 episodes of supraventricular reentrant tachycardia in 31 infants and children were treated with intravenous adenosine at two centers. Adenosine was given as a rapid intravenous bolus injection beginning with a dose of 0.1 mg/kg. If there was persistence of the dysrhythmia dosage was increased in 0.05 mg/kg-steps up to a maximum dose of 0.3 mg/kg if necessary. The median dose required for successful termination of the tachycardias was 0.15 mg/kg. In 26 patients with 48 episodes of regular narrow-QRS-complex tachycardia adenosine was used as the therapeutic agent of first choice. In all patients a shortlasting atrioventricular block occurred within seconds after the administration of adenosine. In 42 of 48 episodes of tachycardia (87%) the dysrhythmias were converted to a stable sinus rhythm. In six episodes (13%) recurrence of the tachycardia was observed immediately. In five children adenosine was used for diagnostic purpose: in three children with wide-QRS-complex tachycardia successful termination with adenosine proved the supraventricular origin of the dysrhythmia. In two children with suspected atrial flutter adenosine-induced atrioventricular block allowed identification of flutter waves in one patient while in the other patient no effect of adenosine was seen. Side-effects such as flush, chest-pain or abdominal pain were frequent but mild and only of a few seconds' duration. No influence of adenosine on blood pressure was noted. Only in one child with previously unknown sinus node dysfunction was a relevant electrophysiologic side effect seen: a prolonged sinus arrest with asystole of 12 seconds' duration occurred after adenosine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

The gene for X-linked myotubular myopathy is located in an 8 Mb region at the border of Xq27.3 and Xq28.

X-linked recessive myotubular myopathy (XLMTM) is a rare and severe neonatal neuromuscular disease characterized by muscle weakness, hypotonia, and respiratory problems. Here we report an extensive linkage analysis in two families with XLMTM. Using 18 markers in the Xq27-Xqter region we found a maximum two-point lod score of Z = 4.00 at theta = 0.00 for the marker II-10 (DXS466). Three recombinations were detected between markers and the disease locus. At the distal side of Xq27.3 a recombination was present in between RNI (DXS369) and VK23b (DXS297), another in between VK23b (DXS297) and II-10 (DXS466), and at the proximal side of Xq28 a recombination in between U6.2 (DXS304) and Cpx67 (DXS134). Combining the results of both families we conclude that XLMTM is located in the 8 Mb(11 cM) region between VK23b (DXS297) and Cpx67 (DXS134).

[Congenital heart defects: prevalence and course during the school years (8 to 16 years)]. / Angeborene Herzfehler: Vorkommen und Verlauf während der Schulzeit (8. bis 16. Lebensjahr).

In continuation of former studies regarding the first year of life and the preschool period, the prevalence and course of congenital heart disease in children during compulsory schooling has been studied. Compared with the preschool period, few cardiac defects are discovered, the prevalence up to 16 years of age being 9.9/1000. The mortality rate (2.7%) and also the rate of spontaneous normalization (4%) is significantly lower (compared to 18.7% and 21% respectively in the preschool period). Medical measures are needed less frequently, with 10 times fewer operations and 15 times fewer heart catheterizations being performed. Apart from the decline of hospital stays, checkups in the outpatient clinic also declined 3-4 times in comparison with the period between birth and school entry. School performance is very good. Only 4% of the children are unable to attend a normal school for cardiac reasons, and the percentage of pupils attending secondary school is higher than normal. In 5% of the children exercise tolerance is decreased due to the cardiac condition. In 85%, the quality of life is normal during the compulsory school period. Impairment is most often caused by additional non-cardiac malformations or very severe heart disease.

[Childhood treatment of paroxysmal supraventricular tachycardia using i.v. adenosine]. / Behandlung der paroxysmalen supraventrikulären Tachykardie im Kindesalter mit Adenosin i.v.

Paroxysmal supraventricular tachycardia is the most frequent significant arrhythmia in the pediatric age group, especially in the first year of life. In neonates and infants there are important limitations for the commonly used drugs such as verapamil and digitalis. In an open Swiss multicentre study we treated 19 children with a total of 29 episodes of tachycardia by means of adenosine i.v. as the drug of first choice. 76% of all the tachycardias were converted, whereas the success rate was 87% if only tachycardias with atrioventricular reentry were considered. The important advantage of adenosine lies in its very short half-life of about 15 seconds, which means that the rare relevant, and the more common mild, side effects are quite limited in duration. A major disadvantage are recurrences in about one third of cases. We conclude that adenosine is an efficient and safe treatment for paroxysmal supraventricular tachycardia in the whole pediatric age group including neonates and infants.

Stress-induced polymorphous ventricular tachyarrhythmias in two brothers: unusual pattern of inheritance in the long QT syndrome.

Two brothers, 10 and 9 years old, are reported who were treated for years with antiepileptic drugs until the cardiac origin of their syncopal attacks was discovered. Our findings are consistent with the diagnosis of long QT syndrome, although no other family members are affected and only intermittent and mostly borderline QT prolongation could be found. Diagnostic difficulties and genetic implications are discussed.

[Value of an electroencephalogram in a patient with transient neurological symptoms]. / Het nut van een elektro-encefalogram bij een patiënt met voorbijgaande uitvalsverschijnselen.

A seven year old boy had several episodes of dysfunction of the left hemisphere. The only sign on physical examination was a very slight facial asymmetry on the right side. The CT scan with and without contrast enhancement was normal. Because of a marked asymmetry of the EEG, duplex scan examination of the carotid arteries was carried out; it showed a flow disturbance of the left carotid artery. Angiography showed a narrowing of the supraclinoidal portion of the internal carotid artery which was considered to be due to angiitis. As the boy was known to have bronchitis and eczema and the blood tests showed a marked increase of eosinophil cells, he was treated with corticosteroids. At follow-up after three months the EEG and the duplex scan were normal. There had been no TIAs since the start of the treatment.