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DeSanto-Shinawi syndrome is a rare neurodevelopmental disorder caused by loss-of-function variants of WAC, located on chromosome 10p12.1. This syndrome is characterized by dysmorphic facial features, intellectual disability, and behavioral problems.In this case report, we present a new deletion case and summarize the clinical data of previously reported individuals, comparing the similarities and differences between cases caused by point mutations versus those which are caused by deletions in the 10p region.Some differential features could facilitate the diagnostic suspicion guiding the optimal diagnostic tests that should be requested in each case scenario.

Background Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder characterized by broad thumbs and halluces. RSTS is caused by mutations in CREBBP and in EP300 genes in 50–60% and 8%, respectively. Up to now, 76 RSTS-EP300 patients have been described. We present the clinical and molecular characterization of a cohort of RSTS patients carrying EP300 mutations. Methods Patients were selected from a cohort of 72 individuals suspected of RSTS after being negative in CREBBP study. MLPA and panel-based NGS EP300 were performed. Results Eight patients were found to carry EP300 mutations. Phenotypic characteristics included: intellectual disability (generally mild), postnatal growth retardation, infant feeding problems, psychomotor and language delay and typical facial dysmorphisms (microcephaly, downslanting palpebral fissures, columella below the alae nasi, and prominent nose). Broad thumbs and/or halluces were common, but angulated thumbs were only found in two patients. We identified across the gene novel mutations, including large deletion, frameshift mutations, nonsense, missense and splicing alterations, confirming de novo origin in all but one (the mother, possibly underdiagnosed, has short and broad thumbs and had learning difficulties). Conclusions The clinical evaluation of our patients corroborates that clinical features in EP300 are less marked than in CREBBP patients although it is difficult to establish a genotype-phenotype correlation although. It is remarkable that these findings are observed in a RSTS-diagnosed cohort; some patients harbouring EP300 mutations could present a different phenotype. Broadening the knowledge about EP300-RSTS phenotype may contribute to improve the management of patients and the counselling to the families.

Background Rubinstein‐Taybi syndrome (RSTS) is a rare congenital disorder characterized by broad thumbs and halluces, intellectual disability, distinctive facial features, and growth retardation. Clinical manifestations of RSTS are varied and overlap with other syndromes’ phenotype, which makes clinical diagnosis challenging. CREBBP is the major causative gene (55%–60% of the cases), whereas pathogenic variants found in EP300 represent the molecular cause in 8% of RSTS patients. A wide range of CREBBP pathogenic variants have been reported so far, including point mutations (30%–50%) and large deletions (10%). Methods The aim of this study was to characterize the CREBBP genetic variant spectrum in 39 RSTS patients using Multiplex Ligation‐dependent Probe Amplification and DNA sequencing techniques (Sanger and Trio‐based whole‐exome sequencing). Results We identified 15 intragenic deletions/duplications, ranging from one exon to the entire gene. As a whole, 25 de novo point variants were detected: 4 missense, 12 nonsense, 5 frameshift, and 4 splicing pathogenic variants. Three of them were classified as of uncertain significance and one of the patients carried two different variants. Conclusion Seventeen of the 40 genetic variants detected were reported for the first time in this work contributing, thus, to expand the molecular knowledge of this complex disorder.

Gorlin syndrome (GS) is a disorder transmitted by dominant autosomal inheritance associated to mutations in PTCH1, the main characteristic of which is the appearance of basal cell carcinomas, together with skeletal abnormalities, odontogenic keratocysts and intracranial tumours.A girl aged 3 years and 10 months, who was admitted due to acute ataxia. Some of the more striking features in the patient's personal history include psychomotor retardation and a family history of suspected GS in the mother as a result of a maxillary cyst. An examination revealed macrocephaly with a prominent forehead and hypertelorism, as well as nevus. A genetic study for GS was requested, in which mutation c.930delC was detected in exon 6 of the PTCH1 gene in heterozygosis.In GS there is an increase in the likelihood of developing basal cell carcinomas and strict dermatological monitoring is necessary. A clinical neurological follow-up and also magnetic resonance imaging scans are needed for an early diagnosis of intracranial tumours, especially in the case of medulloblastomas. Odontogenic keratocysts, other skin disorders, and cardiac and ovarian fibromas are characteristic, as are skeletal abnormalities, which require regular clinical and neuroimaging controls and treatment if needed, but radiation must be avoided. GS is a rare disorder, but it must be suspected in the presence of characteristic alterations. It requires a multidisciplinary follow-up, and it is also necessary to establish a protocol on how to act so as to allow early diagnosis and treatment of the potentially severe complications deriving from this disease.Sindrome de Gorlin en la edad pediatrica.Introduccion. El sindrome de Gorlin (SG) es un trastorno de herencia autosomica dominante asociado a mutaciones en el gen PTCH1, cuya principal caracteristica es la aparicion de carcinomas basocelulares, unido a anomalias esqueleticas, queratoquistes odontogenicos y tumores intracraneales. Caso clinico. Niña de 3 años y 10 meses, ingresada por ataxia aguda. Destacan como antecedentes personales retraso psicomotor y como antecedentes familiares la sospecha de SG en la madre por quiste maxilar. En la exploracion, se aprecia macrocefalia con frente prominente e hipertelorismo, asi como nevo. Se solicita estudio genetico de SG, en el que se detecta la mutacion c.930delC en el exon 6 del gen PTCH1 en heterocigosis. Conclusiones. En el SG hay un aumento de la susceptibilidad al desarrollo de carcinomas basocelulares y es preciso un estrecho control dermatologico. Es necesario un seguimiento neurologico clinico y de imagen, mediante resonancia magnetica, para el diagnostico precoz de tumores intracraneales, fundamentalmente el meduloblastoma. Tambien son caracteristicos los queratoquistes odontogenicos, otras alteraciones cutaneas, fibromas cardiacos y ovaricos, asi como anomalias esqueleticas, que precisan controles clinicos y de imagen periodicos, y tratamiento en caso de ser necesarios, pero debe evitarse la radiacion. El SG es un trastorno poco frecuente, que se debe sospechar ante la presencia de alteraciones caracteristicas. Es necesario un seguimiento multidisciplinar, asi como establecer un protocolo de actuacion, para un temprano diagnostico y tratamiento de las complicaciones potencialmente graves derivadas de esta enfermedad.

Global developmental delay (GDD) and intellectual disability (ID) are common reasons for consultation in paediatric neurology. Results from aetiological evaluations of children with GDD/ID vary greatly, and consequently, there is no universal consensus regarding which studies should be performed.We review our experience with determining aetiological diagnoses for children with GDD/ID who were monitored by the paediatric neurology unit over the 5-year period between 2006 and 2010.During the study period, 995 children with GDD/ID were monitored. An aetiological diagnosis was established for 309 patients (31%), but not in 686 (69%), despite completing numerous tests. A genetic cause was identified in 142 cases (46% of the total aetiologies established), broken down as 118 cases of genetic encephalopathy and 24 of metabolic hereditary diseases. Our data seem to indicate that diagnosis is easier when GDD/ID is associated with cerebral palsy, epilepsy, infantile spasms/West syndrome, or visual deficit, but more difficult in cases of autism spectrum disorders. Genetic studies provide an increasing number of aetiological diagnoses, and they are also becoming the first step in diagnostic studies. Array CGH (microarray-based comparative genomic hybridisation) is the genetic test with the highest diagnostic yield in children with unexplained GDD/ID.The cost-effectiveness of complementary studies seems to be low if there are no clinically suspected entities. However, even in the absence of treatment, aetiological diagnosis is always important in order to provide genetic counselling and possible prenatal diagnosis, resolve family (and doctors') queries, and halt further diagnostic studies.

We present the case of a 13 year-old patient diagnosed with fibromuscular dysplasia (FMD) by angiographic study, with "string of beads" image of internal carotid, after undergoing two ischemic strokes in nine days. Conservative treatment with acetylsalicylic acid at antiaggregant doses was decided. Twenty months later the clinical progress is favorable without presenting any new episodes. FMD is a very uncommon cause of stroke in childhood. Little is known about its etiology. In spite of it usually being an asymptomatic disease, it must be considered in cases of repeated or inexplicable strokes. Its prognosis and treatment is controversial, due to the limited number of pediatric patients with this pathology.

The prognosis of epilepsy is essentially determined by its aetiology and a poorer prognosis is generally associated with an early onset of the seizures.In this study we review our experience in epilepsies in children born after 1st January 1997 and who had their first acute non-symptomatic seizure before 31st March 2007 and between the ages of 3 and 12 months. Special attention is given to the analysis of cases of remote non-symptomatic epilepsies.Of the children born in that period, 267 were diagnosed with epilepsy, and the first seizure occurred between 3 and 12 months of age in 69 cases: 39 of which were symptomatic and 30 were cryptogenic and idiopathic epilepsies. West's syndrome/childhood spasms were observed in 20 cases (17 of the symptomatic cases and three of the cryptogenic and idiopathic patients). The cryptogenic and idiopathic cases were divided into three groups depending on their electroencephalogram pattern: nine generalised, 18 with no generalised alterations and three hypsarrhythmias. In addition, the three groups were analysed taking into account three degrees of psychomotor development: normal, slight retardation and moderate/severe retardation. None of the non-generalised cases presented severe psychomotor retardation, whereas 78% of the generalised and 33% of those with West's syndrome developed an important degree of retardation in their course.Our experience is compatible with the existence of epilepsies that have their onset in the early months of life and a good prognosis, which is important when it comes to the information and therapeutic approaches in cases of remote non-symptomatic epilepsy.

In neuropaediatrics, the aetiological diagnosis rarely allows a causal treatment to be established. In many cases, all we can offer is referral to early intervention (EI) and botulinum toxin type A (BTA). The only requirement before starting both interventions is a functional or syndromic diagnosis.Here we analyse the experience gained from an EI programme carried out in the region of Aragon since February 2003 and with the BTA service in the Neuropaediatric Unit of the Hospital Universitario Miguel Servet since November 2003.By the end of 2007, 2629 requests had been made for admission to the EI programme and in the year 2007 a total of 702 children were treated. In four years and four months 122 children with infantile cerebral palsy (ICP) were infiltrated with BTA, with positive results in 70% of cases and mild, transient side effects in 13.1%.The children, parents and professionals involved all view EI and BTA with satisfaction. Neuropaediatrics is one of the medical specialties that are best suited to child development and early intervention centres (CDIAT). The neuropaediatrician participates in all the stages of the EI: detection, diagnosis, information and intervention. He or she may act as the coordinating and homogenising element in EI, that is to say, as a link between CDIAT and health care services. Neuropaediatricians are also essential in EI training and education, in family training, information and awareness campaigns, primary care, social services and nurseries. Treatment with BTA cannot be viewed as an isolated technique, but instead as part of a programme in which physiotherapy, orthosis and sometimes surgery play a fundamental role. Coordination among the different professionals involved in treating the child with ICP is absolutely crucial.

The quality of the health care in a major part of neuropaediatrics benefits from appropriate communication and strategies that have been agreed with primary care (PC) paediatricians.We analyse the children who were assessed in the Neuropaediatric service at the Hospital Universitario Miguel Servet in Saragossa over a period of eight years and we also discuss the most important courses of action followed in the most prevalent problems.Eight reasons for visiting accounted for 86% of the total number: paroxysmal disorders (33%), headache (27%), psychomotor retardation (11.5%), alterations affecting the shape or size of the head (5.6%), problems at school and/or attention deficit (4.5%), behavioural disorders (4.25%), gait disorders (3.5%) and perinatal distress (3.4%). The most frequent diagnoses are headaches/migraines (26%), non-epileptic paroxysmal disorders (16.5%), prenatal encephalopathy (10.5%), epilepsy (8%), mental retardation (7.5%), infantile cerebral palsy (4.6%), cryptogenic attention deficit hyperactivity disorder (ADHD) (3.8%) and cryptogenic autism (3.6%).The PC paediatrician working in close relation with the children and their families in all cases is the person mainly responsible for conducting a follow-up on some of the most prevalent problems, such as headaches, many non-epileptic paroxysmal disorders and ADHD. The processes must be established, clearly specified, based on the best evidence, with the participation and within reach of all the professionals involved, in order to favour homogeneity and keep variability in the interventions to a minimum. Channels of communication, including the information and communications technologies, need to be set up to allow health professionals to be permanently up-to-date and capable of controlling their patients in the best possible way.

The aetiology and clinical features of peroxisomal diseases vary widely. An altered very-long-chain fatty acid (VLCFA) profile is commonly found in many of these diseases, and this makes it easier to point the diagnosis in the right direction.We review our experience in the diagnosis of cases of peroxisomal diseases with an altered VLCFA pattern; these were determined in serum only when there was a strong clinical suspicion up to the end of 1998, when their quantification by chromatography was introduced into our laboratory.The neuropaediatric database included 10,239 cases between May 1990 and 1st October 2007. Ten cases of peroxisomal disease with an altered VLCFA pattern were identified, all of them males. There were two cases of Zellweger syndrome spectrum, one unclassified peroxisomal oxidation defect and seven X-linked adrenoleukodystrophies (four with neurological compromise and three with no neurological damage; two were identified in siblings of patients and the other due to the presence of Addison's syndrome).In our 10 cases, the diagnosis was guided by the clinical or familial features that led to the determination of VLCFA. Being able to determine VLCFA makes early systematic diagnosis of patients possible. At present, VLCFA determination is performed when there is a clinical suspicion of Zellweger spectrum, suspected X-linked adrenoleukodystrophy/adrenomyeloneuropathy of unclear causation, Addison's disease, both in males and females, and above all in cases of chronic encephalopathy of unknown causation, with or without prenatal onset.

We review retrospectively the clinical histories of patients who were immediately switched from carbamazepine (CBZ) to oxcarbazepine (OXC), being administered a minimum of 1.3 times the CBZ dosis in 2 daily dosis of OXC.The immediate switching was carried out in 22 paediatric cases. 17 patients were taking CBZ in monotherapy and 5 in politherapy. The change was made in 20 cases to lower the number of seizures (and to avoid side effects in 4 of them), and in 2 only to reduce drowsiness and fatigue. The average change was from 18.62 mg/kg of CBZ to 28.89 mg/kg of OXC. The medium change rate was 1.6:1 (maximum: 2:1).In 19 cases there were no side effects. With one boy, the essential tremor worsened and two girls became more tired and drowsy. Three experienced less drowsiness and one less weight increase. Twelve cases showed no seizure changes. Five cases became immediately seizure-free, three of them for a prolongated time. There was a reduction in seizure frequency in 2 cases, with posterior disappearance in one of them. Three cases experienced a reduction in seizure intensity. In two cases OXC was stopped after 24 seizure-free months. Fourteen patients were still taking OXC, 8 in monotherapy, with a mean follow-up of 31.5 months.Given the potential benefits, ease and good tolerability, we advise trying with immediate switching to OXC, before adding another antiepileptic drug to CBZ.

As result of our aim to improve the quality standard of our emergency system, work has been carried out in relation to the development and monitorization of effective clinical protocols in the department of paediatric practice.An evidence based review approach was taken to design a clinical protocol about Bell's palsy condition for the paediatric emergency department. Previous protocol approved in March 2003 was reviewed accordingly with the new designed protocol's quality standards. The Bell's palsy cases reported since March 2003 until June 2006 to paediatric emergency department were analyzed.A total of 27 patients affected by Bell's palsy were reported to the hospital's emergency department. Facial expression was described in 85.19% of the cases. Cranial nerves normal function was reported in 77.78%. Fundoscopic examination was described in 77.78% and otoscopic findings in 44.44%; the absence of herpes vesicles was analyzed only in 11.11%. All patients received steroid therapy (prednisone) and the treatment resulted in the complete recovery. The mean time to resolution was 58.6 days.In order to improve hospital's quality standards, clinical protocols should be designed and verified regularly to ensure the proper performance. Medical auditing also contributes to improve effectiveness in health attendance.