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The 4q deletion syndrome defines a disorder, which may involve patients affected by either the deletion of the interstitial region from the centromere to 4q31 or by the deletion of the terminal region from 4q31 to 4qter. Here, we describe clinical phenotypes of two unrelated children of the same age followed at the same time, with case 1 presenting with 4q interstitial and case 2 with terminal 4q deletion, and compare them each other and with those reported in the literature. Both children showed complex, heterogeneous clinical manifestations, including craniofacial features, pre-postnatal growth failure, speech and developmental delay. In case 2, thyroid and cholesterol dysfunction were also found. Analyzing these data, clinical differences between interstitial and terminal 4q deletions are scanty and no significant phenotype differences were found between the 4q regions deleted as observed in the comparison of the two children and the related cases of the literature. The term 4q deletion syndrome - inclusive for both the interstitial and terminal 4q regions deleted - seems to be appropriate. To note, the dysfunction of cholesterol metabolism and thyroid presented by case 2 may be clinically worthwhile, whether confirmed by other observations. [ABSTRACT FROM AUTHOR]

FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with "new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction. Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement. FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

Zhu‐Tokita‐Tachenouchi‐Kim syndrome (ZTTK) is a recently recognized malformation syndrome presenting with craniofacial dysmorphism, developmental delay/intellectual disability, seizures, anomalies involving brain white matter, and other body‐organs. In humans, the disorder is linked to the loss‐of‐function variants in the SON gene (MIM# 617140). Herewith, a new case of this syndrome is reported in a 2‐year‐old Caucasian child who presented the classical clinical features of the ZTTK syndrome in association with hydrocephalus and Chiari malformations type 1 an anomaly previously unreported. Exome analysis showed a de novo heterozygous variant in SON gene. Literature review of similar cases is reported. [ABSTRACT FROM AUTHOR]

Background: The BUB 1 mitotic checkpoint serine/threonine kinase B (BUB1B) gene encodes a key protein in the mitotic spindle checkpoint, which acts as a surveillance mechanism, crucial for the maintenance of the correct chromosome number during cell deviation. Mutations of BUB1B gene are linked to mosaic variegated aneuploidy 1 (MVA1) syndrome, a rare autosomal recessive disorder characterized by widespread mosaic aneuploidies, involving different chromosomes and tissues. MVA1 is clinically characterized by intrauterine growth restriction, post-natal growth retardation, and severe neurologic impairment including microcephaly, developmental delay/intellectual disability, epileptic seizures, and generalized hypotonia. Malignancies are also serious sequelae associated with the disorder. We reported on a case of two-year-old Italian girl with MVA1 who shows severe neurologic impairment, microcephaly and epileptic seizures. Materials and methods: Clinical data collection and genetic diagnosis of the patient were assessed. Mutational analysis covers the chromosomal microarray analysis, the gene methylation pattern studied using the methylation-specific multiplex ligation-dependent probe amplification, and the family-based Whole Exome Sequencing (WES). A literature research based on reported cases of MVA and premature chromatid separation was also included. Results: Karyotyping has revealed 12% of mosaics in the patient who carries a novel variant in BUB1B gene (c.2679A > T, p.Arg893Ser) detected by WES. Thirty-one cases of MVA1 including the present report, and four prenatally diagnosed cases with MVA1 were selected and inspected. Conclusion: Clinical and genetic findings reported in the girl strongly suggest a new MVA1 genotype–phenotype correlation and lead to a reappraisal of a severe syndrome. Diagnosis and in-depth follow-up provided worthwhile data. [ABSTRACT FROM AUTHOR]

Acute autoimmune encephalitis is a severe neurological disorder presenting with altered level of consciousness, confusion, irritability, headache, vomiting, and in some cases seizures. An infective event precedes by 1–2 weeks the onset of the symptoms. Cognitive impairment is considered the cardinal symptom. The autoimmune encephalitis comprises an increasingly group of inflammatory brain disorder caused by an underlying abnormal immune response to the CNS to the infective agent. In children, several antibodies have been recorded as causative agent. Among these, GAD65, MOG, and NMDAR antibodies are more commonly reported and with less frequency, the Dopamine-2 receptor, GABA A receptor, GABA B receptor, and Glycinereceptorandm-GluR5. We report here a 10-year-old male with acute autoimmune encephalitis with altered status of consciousness and severe cerebral involvement at the brain-MRI. Serum and cerebrospinal fluid disclosed the presence of anti-AMPA-GluR3 antibodies suggesting a possible pathogenetic correlation with the disorder presented by the proband. Precocious treatment with intravenous methylprednisolone and immunoglobulin resulted in progressive but constant improvement. At 3-month follow-up, the clinical condition of the child and the neuro-radiological brain anomalies returned to the normal. At the 2-year follow-up, no recurrence or other disturbances were reported. [ABSTRACT FROM AUTHOR]

Background: Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability. Case presentation: Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature. Conclusions: Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity. [ABSTRACT FROM AUTHOR]

Vitamin B12 is a water-soluble vitamin that plays a fundamental role as an essential cofactor for two enzymes responsible for the production of succinyl-CoA and methionine. Vitamin B12 deficiency can occur in infants and may be related to the breastfeeding mother's adherence to a vegan diet or somatic diseases in the mother. It should be differentiated from inborn errors of vitamin B12 metabolism. Herein, we report the cases of three infants with West syndrome; all three were breastfed by mothers who followed a strict vegan diet. In one of the three infants, West syndrome developed during treatment with vitamin B12 and normalization of the vitamin B12 level. Early treatment and replacement therapy are worthwhile to prevent serious neurological problems and to improve the patient's clinical course. [ABSTRACT FROM AUTHOR]

SARS‐CoV‐2 (Severe Acute Respiratory Syndrome, Coronavirus, type 2) is the virus responsible for the global pandemic of Coronavirus disease 2019 (COVID‐19) that began in China in December 2019. The variability of nasal olfactory symptoms in pediatric patients is interlinked with possible warning signs, including respiratory, gastrointestinal, ocular, or dermatological symptoms. Skin findings in patients with COVID‐19 can range from petechiae to papulovesicular rashes to diffuse urticaria and can be confused with rashes of non‐COVID‐19 conditions. These lesions typically appear early during COVID‐19 and are thought to be secondary to viral replication or circulating cytokines. Herein, we discuss two pediatric cases, presenting with skin lesions, which tested positive for SARS‐CoV‐2, thus, briefly reviewing current literature for similar reports and related management. Although these lesions heal spontaneously in most cases, an adequate "targeted" therapeutic approach can shorten the time and the discomfort of the skin disease. [ABSTRACT FROM AUTHOR]

Since its first clinical description (on his son) by William James West (1793–1848) in 1841, and the definition of the classical triad of (1) infantile spasms; (2) hypsarrhythmia, and (3) developmental arrest or regression as "West syndrome", new and relevant advances have been recorded in this uncommon disorder. New approaches include terminology of clinical spasms (e.g., infantile (IS) vs. epileptic spasms (ES)), variety of clinical and electroencephalographic (EEG) features (e.g., typical ictal phenomena without EEG abnormalities), burden of developmental delay, spectrum of associated genetic abnormalities, pathogenesis, treatment options, and related outcome and prognosis. Aside the classical manifestations, IS or ES may present with atypical electroclinical phenotypes (e.g., subtle spasms; modified hypsarrhythmia) and may have their onset outside infancy. An increasing number of genes, proteins, and signaling pathways play crucial roles in the pathogenesis. This condition is currently regarded as a spectrum of disorders: the so-called infantile spasm syndrome (ISs), in association with other causal factors, including structural, infectious, metabolic, syndromic, and immunologic events, all acting on a genetic predisposing background. Hormonal therapy and ketogenic diet are widely used also in combination with (classical and recent) pharmacological drugs. Biologically targeted and gene therapies are increasingly studied. The present narrative review searched in seven electronic databases (primary MeSH terms/keywords included West syndrome, infantile spasms and infantile spasms syndrome and were coupled to 25 secondary clinical, EEG, therapeutic, outcomes, and associated conditions terms) including MEDLINE, Embase, Cochrane Central, Web of Sciences, Pubmed, Scopus, and OMIM to highlight the past knowledge and more recent advances. [ABSTRACT FROM AUTHOR]

Objectives: To report a case series of children presenting with episodes of abrupt onset psychotic symptoms presumably linked to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Children/adolescents were selected among the group of individuals affected by clinical diagnosis of PANDAS/PANS. One group was selected by affected individuals coming from the Center UMDNJ-New Jersey Medical School, New Jersey, USA and the other from the Department of Pediatrics Catania University, Italy. Child health Questionnaire Parent form 50 was given to parents to describe children's quality of life. Results: Among the group of individuals with PANDAS/PANS disorders, eight children/adolescents were selected, six coming from the UMDNJ-New Jersey and two from Catania, University centers showing among the other typical manifestations severe episodes of abrupt onset of psychotic symptoms. Conclusions: Severe psychotic symptoms may be considered one among the other neuropsychiatric clinical manifestations presenting in individuals with PANDAS/PANS syndromes. [ABSTRACT FROM AUTHOR]

Background: Mutations in GABRB3 have been identified in subjects with different types of epilepsy and epileptic syndromes, including West syndrome (WS), Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), myoclonic‐atonic epilepsy (MAE), and others. Methods and results: We herewith report on a girl affected by DS, who has been followed from infancy to the current age of 18 years. Next‐generation sequencing (NGS)‐based genetic testing for multigene analysis of neurodevelopmental disorders identified two likely de novo pathogenic mutations, a missense variant in GABRB3 gene (c.842 C>T; p.Thr281IIe) and a nonsense variant found in BBS4 gene (c.883 C>T; p.Arg295Ter). Conclusion: A likely relationship between the novel GABRB3 gene variant and the clinical manifestations presented by the girl is proposed. Previously, one case of DS and two of DS‐like linked with GABRB3 mutations have been reported. To the best of our knowledge, this is the first report of DS associated with this novel variant. A literature review of clinical cases with various types of epileptic encephalopathies (EEs) related to GABRB3 mutations is reported. Our study explores a likely new gene‐phenotype relationship between a novel GABRB3 gene variant and the clinical manifestations of Dravet syndrome (DS). We, herewith, report on a long‐term follow‐up of a girl affected by DS, who harbors a novel likely pathogenic variant of GABRB3. A literature review of cases with various types of epileptic encephalopathy related to GABRB3 mutations is discussed. [ABSTRACT FROM AUTHOR]

Background: Wilson disease (WD) is an Autosomal-Recessive disorder due to mutations of ATP7B gene on chromosome 13q14.3. Inadequate protein function leads to low ceruloplasmin blood levels and copper accumulation in liver, basal ganglia and chornea. Main clinical manifestations are hypertransaminasemia, tremors, dysarthria, dystonia and psychiatric symptoms. The phenotypic variability in WD is considerable and its onset can be heterogeneous: the most common type in childhood is the hepatic involvement, followed by the neurological one or others. The presence of a genotype-phenotype correlation has not yet been fully demonstrated. The phenotypic variability may be explained by the intervention of other modifier genes regulating copper metabolism in the presence of mutations ATP7B. Case presentation: A streaking phenotypic variability was observed in two Sicilian sisters carrying the same genotype for ATB7B gene [c.3207C > A / c.3904-2A > G]. Although both started to present signs at age 10 years, onset was characterized by neurological signs in the first (tremors, motor incoordination, language and cognitive impairment), while liver involvement has been the only sign in the other. They started the same chelation therapy. After a 20-year follow-up the former is severely affected (MRI evidence of basal ganglia copper deposits and hyperchogenic liver, thrombocytopenia), while the latter presents only a moderate liver enlargement. In literature, the splice mutation c.3904-2A > G is also reported in Egypt population, associated with acute liver failure or chronic hepatic disease, and it could be typical of Mediterranean area, not being reported in other geographical zones. Conclusion: Based on our clinical experience in Eastern Sicily, there is a considerable phenotypic variability in WD, even in the presence of an identical genotype. The mutation c.3904-2A > G could be associated with this phenotypic variability in Mediterranean population, but further studies should be conducted. This condition could be explained by the intervention of modifier genes regulating copper metabolism in the presence of defective ATP7B protein function. Further investigations on their role by Next Generation Sequencing or Whole Exome Analysis might have a profound impact on patients' management and in particular on therapy. [ABSTRACT FROM AUTHOR]

Background: Deletions in chromosome 15q13 have been reported both in healthy people and individuals with a wide range of behavioral and neuropsychiatric disturbances. Six main breakpoint (BP) subregions (BP1‐BP6) are mapped to the 15q13 region and three further embedded BP regions (BP3‐BP5). The deletion at BP4‐BP5 is the rearrangement most frequently observed compared to other known deletions in BP3‐BP5 and BP3‐BP4 regions. Deletions of each of these three regions have previously been implicated in a variable range of clinical phenotypes, including minor dysmorphism, developmental delay/intellectual disability, epilepsy, autism spectrum disorders, behavioral disturbances, and speech disorders. Of note, no overt clinical difference among each group of BP region deletions has been recorded so far. Methods: We report on a four‐member family plus an additional unrelated boy affected by a BP3‐BP5 deletion that presented with typical clinical signs including speech delay and language impairment. A review of the clinical features associated with the three main groups of BP regions (BP4‐BP5, BP3‐BP5, and BP3‐BP4) deletions is reported. Results: Array‐CGH analysis revealed in the mother (case 1) and in her three children (cases 2, 3, and 4), as well as in the unrelated boy (case 5), the following rearrangement: arr (hg19) 15q13.1‐q13.3 (29.213.402–32.510.863) x1. Conclusion: This report, along with other recent observations, suggests the hypothesis that the BP region comprised between BP3 and BP5 in chromosome 15q13 is involved in several brain human dysfunctions, including impairment of the language development and, its deletion, may be directly or indirectly responsible for the speech delay and language deficit in the affected individuals. [ABSTRACT FROM AUTHOR]

Optic neuropathy consists of several etiological events. The primary etiologies of its acute form include optic neuritis, ischemic optic neuropathy, inflammatory (nondemyelinating) disorders, and trauma. Its subacute and chronic forms are most often linked to compressive, toxic, nutritional, or hereditary-genetic causes. Visual loss, dyschromatopsia, and visual field defects are the presenting symptoms. The Onodi cell (sphenoethmoidal air cell) is an anatomic variant located laterally and superior to the sphenoid sinus; it is closely related to the optic nerve. Onodi cell disorders are rare and may be unnoticed in differential diagnoses of patients with ocular and neurological manifestations. Here, we present the case of a 12-year-old boy with headache and acute loss of sight characterized by hemianopsia in the left eye and retrobulbar optic neuropathy caused by left sphenoethmoidal sinusitis with the presence of Onodi cell inflammation. The diagnosis was confirmed by multilayered paranasal computed tomography and cerebral magnetic resonance imaging. Therapeutic treatment resulted in gradual improvement: at the 2-week follow-up, the patient no longer had headaches and his visual acuity returned to normal. Inflammation of Onodi cells should be considered in children with headache and abnormal vision. [ABSTRACT FROM AUTHOR]

Nontraumatic atlantoaxial subluxation, also known as Grisel syndrome, is a rare disease that usually affects children. The typical presentation is torticollis in patients with a history of surgical operations or airway infections. We describe 5 patients with Grisel syndrome, referring to medical care for a torticollis, a few weeks after an airway infection, with no trauma associated. Radiologic confirmation of the diagnosis, with computed tomography and magnetic resonance imaging studies, was carried out. The patients were treated with external immobilization for 3 months, followed by surgical fixation in the case of recurrence after collar removal or inveterate subluxation. We performed a review of the literature to define the best management of this disease. Management of Grisel syndrome depends on the degree of subluxation basing on the Fielding and Hawkins classification. The initial nonsurgical management consists of close reduction and immobilization. Surgical fixation is indicated in cases of conservative treatment failure. [ABSTRACT FROM AUTHOR]

Abstract Array-based comparative genomic hybridization is a routine technology that helps clinicians in the diagnostic evaluation of individuals presenting with developmental delay or malformation anomalies. With this technique, several patients affected by microdeletion 2p15-p16.1 have been reported and this anomaly has been recognized as a distinct syndrome. In contrast, clinical features of patients with microduplication in the same region have been registered mainly in clinical and genetic data-bases and to date just a single patient has been reported in detail in the literature. A 12-year-old boy with 2p15-p16.1 microduplication presented with moderate neurodevelopment delay, epileptic seizures, behavioral disturbances, and minor dysmorphic features. The role of 2p15-p16.1 duplication in this case, and the others published in data-bases with a similar molecular duplication, are discussed. [ABSTRACT FROM AUTHOR]

Choledochal cysts are rare cystic dilatations of the bile ducts, which are commonly found in children. We report two young patients affected by this anomaly. The clinical symptoms of the patients were minimal: mild pain localized in the upper-right quadrant and a serum increase in transaminases. Both of the patients were affected by type I choledochal cysts (B and A, respectively, according to the Todani classification). The diagnosis was made using abdominal ultrasound and then confirmed by MRI. We wish to emphasize the relevant contribution of ultrasound as an easy, reliable, rapid, low-cost modality for the diagnosis of choledochal cysts. [ABSTRACT FROM AUTHOR]

Background: Woolly Hair is an uncommon congenital anomaly of the scalp hair presenting with strongly coiled hair involving a localized area of the scalp or covering the entire side and occurring in non-black people. Isolated or localized wooly hair is usually benign and is not related to other disorders and/or complications. On the contrary, the generalized type may be related to disorders and syndromes affecting heart, cutis, liver and gastrointestinal organs. Among the syndromes presenting with wooly hair, the most known are the Naxos syndrome, the Carvajal- Huerta syndrome, the wooly hair/hypotrichosis, the ectodermal dysplasia-skin fragility, the tricho-hepato-enteric syndrome. Case presentation: To our knowledge, no cases of wooly hair syndromes has been associated to neurologic involvement. Among the clinical notes of patients admitted in the Pediatric Units of the Catania University, we have selected four individuals presenting wooly hair, who showed different clinical features and course: case 1 presenting with a localized wooly hair type; case 2, member of a family affected by WH with autosomal dominant inheritance, not associated to complications; case 3, a wooly hair patient who displayed a progressive, severe form of Rasmussen's encephalitis with fatal evolution, and case 4, wooly hair associated to brain malformation and drug-resistant epilepsy. Conclusions: With this report, we aim to underline the wide spectrum of clinical presentation of individuals with WH and in particular we wish to give an annotation on a possible association of WH with severe neurologic disorders. [ABSTRACT FROM AUTHOR]

Background: Ataxia is a sign of different disorders involving any level of the nervous system and consisting of impaired coordination of movement and balance. It is mainly caused by dysfunction of the complex circuitry connecting the basal ganglia, cerebellum and cerebral cortex. A careful history, physical examination and some characteristic maneuvers are useful for the diagnosis of ataxia. Some of the causes of ataxia point toward a benign course, but some cases of ataxia can be severe and particularly frightening. Methods: Here, we describe the primary clinical ways of detecting ataxia, a sign not easily recognizable in children. We also report on the main disorders that cause ataxia in children. Results: The causal events are distinguished and reported according to the course of the disorder: acute, intermittent, chronic-non-progressive and chronic-progressive. Conclusions: Molecular research in the field of ataxia in children is rapidly expanding; on the contrary no similar results have been attained in the field of the treatment since most of the congenital forms remain fully untreatable. Rapid recognition and clinical evaluation of ataxia in children remains of great relevance for therapeutic results and prognostic counseling. [ABSTRACT FROM AUTHOR]

Array-comparative genomic hybridization (Array-CGH) has been proposed as the first efficient approach to scan the entire genome for variations in DNA copy number. This diagnostic method is based on the study of total genomic DNA isolated from any sample and reference cell populations, differentially labelled and hybridized to DNA microarrays. The method has been initially applied in clinical genetics research and has recently also been used in cancer research, as tumor genomes have a wide variety of copy number phenotypes, indicating different types of genetic instability. In this field, array-CGH has been demonstrated to be an efficient diagnostic method to provide information on the location of important cancer genes. Recently the use of array-CGH has been expanded, including the analysis of constitutional abnormalities, to diagnose subtending mutations of neurologic diseases, with promising results in diagnosing genetic mutations otherwise not evident with other genetic tests. We performed a prospective study on the efficiency of array-CGH in the genetic-molecular diagnosis of pediatric patients affected by developmental delay and mental retardation associated with clinical signs of dimorphism and/or other relevant neurological symptoms. In our study, we had a detection rate of 22.71% by array-CGH analysis and we were able to take more precise genetic information for microdeletion and microduplication of our cohort of patients with developmental delay and/or idiopathic mental retardation and/or dimorphic face and/or epilepsy. In our opinion, we think that these findings would be helpful in early diagnosis and family genetic counseling, above all in those clinical neurologic cases in which other diagnostic tests have not succeed in performing a diagnosis. [ABSTRACT FROM AUTHOR]

Congenital melanocytic nevi (CMN) are observed frequently in children. The anomalous skin shows a widely variable clinical expression not only in the anatomic location, but also in color, morphology and superficial structure. According to the width CMN are distinguished in small, medium, large or giant. Aside the cosmetic problem and its psychological implications, CMN may present with severe complications consisting of malignant transformation and/or central nervous system involvement. We report on a 3-month old infant with an extensive CMN in the left leg, which extended from the lower portion of the knee to the foot, with satellite nevi. Concomitant with the extensive nevi in the same district a remarkable reduction in size was present, and involved the adipose and muscle tissues, contributing to a counterpart diameter difference of 5 cm, without bone involvement. Melanocytic nevi and soft tissue undergrowth in the leg is a usual association; a pathogenic explanation on the anomaly involving concomitantly the skin and the underneath soft tissues is advanced. [ABSTRACT FROM AUTHOR]

Neurocutaneous disorders represent a heterogeneous group of conditions affecting the skin (with pigmentary/vascular abnormalities, hamartomas or tumors) and the central and peripheral nervous systems. In recent years, besides the well-known neurocutaneous diseases (e.g., the different forms of neurofibromatosis, tuberous sclerosis complex, Sturge-Weber syndrome and mosaic pigmentary/hamartomatous disorders), new distinctive syndromes have been characterized, extending our knowledge on the spectrum of these conditions. The concurrent presence of pigmentary abnormalities (both of the hypo- and hyperpigmented type), and primary microcephaly has not been commonly reported. We report on a 4.5-year-old girl with primary microcephaly, who had in addition moderate to severe developmental delay, behavioral and stereotypic abnormalities and a cutaneous pattern of paired hypo- and hyperpigmented lesions variously distributed over the body, particularly on the trunk. Failure to thrive and mild facial dysmorphic features were also present. To our knowledge, this complex malformation (neurocutaneous) phenotype has not been previously reported. [ABSTRACT FROM AUTHOR]

Hypertrichosis is defined as an excessive growth in body hair beyond the normal variation compared with individuals of the same age, race and sex and affecting areas not predominantly androgen-dependent. The term hirsutism is usually referred to patients, mainly women, who show excessive hair growth with male pattern distribution. Hypertrichosis is classified according to age of onset (congenital or acquired), extent of distribution (generalized or circumscribed), site involved, and to whether the disorder is isolated or associated with other anomalies. Congenital hypertrichosis is rare and may be an isolated condition of the skin or a component feature of other disorders. Acquired hypertrichosis is more frequent and is secondary to a variety of causes including drug side effects, metabolic and endocrine disorders, cutaneous auto-inflammatory or infectious diseases, malnutrition and anorexia nervosa, and ovarian and adrenal neoplasms. In most cases, hypertrichosis is not an isolated symptom but is associated with other clinical signs including intellective delay, epilepsy or complex body malformations. A review of congenital generalized hypertrichosis is reported with particular attention given to the disorders where excessive diffuse body hair is a sign indicating the presence of complex malformation syndromes. The clinical course of a patient, previously described, with a 20-year follow-up is reported. [ABSTRACT FROM AUTHOR]

Microcephaly is defined as a head circumference measurement of 2 or 3 standard deviations below the mean for age and sex. However, distinguishing the value of -2 or -3 standard deviations as a cutoff is relevant in the clinical practice, since the limit of -3 standard deviations is more frequently associated with cognitive impairment. The use of ultrasound scans in pregnancy has allowed the identification of subjects with a measurement of the head circumference at the limit of the cutoff for gestational age, but who do not subsequently show cognitive delay. The same is true for newborns with a -2 to -3 standard deviations cutoff, and without anomalous clinical signs, for which a cognitive delay is not easily diagnosed. In this case, to define an infant as being affected by microcephaly (with a prognosis usually recognized as harmful) may be unnecessarily distressful for parents or caregivers. In the cases mentioned, resuming the word "small head" instead of microcephaly to define such subjects could be more appropriate and more appreciated. [ABSTRACT FROM AUTHOR]

There is an ample evidence that hypopigmentation of the skin along the Blaschko's lines is frequently associated with neurological disorders. Nowadays, the term 'Hypomelanosis of Ito' (HI) is applied when, together with the cutaneous lesions, various and multisystem organs are involved. Among these, the most frequent are cerebral manifestations, such as cognitive delay and epileptic seizures. For this reason, hypomelanosis of Ito has been included in the group of neurocutaneous syndromes, neurologic manifestations being one of the most frequent. Epileptic seizures have been reported in patients with this disorder, but in a very few particular attention has been focused on the type and frequency of epilepsy and on the response to the treatment. Herein, we report on five patients with HI who showed episodes of epileptic seizures with onset in childhood, in absence of malformative anomalies except for the skin lesions. A survey on the frequency and types of epileptic seizures in HI children and in the literature is reported. [ABSTRACT FROM AUTHOR]

The authors report a wide and updated revision of hydranencephaly, including a literature review, and present the case of a patient affected by this condition, still alive at 36 months. Hydranencephaly is an isolated and with a severe prognosis abnormality, affecting the cerebral mantle. In this condition, the cerebral hemispheres are completely or almost completely absent and are replaced by a membranous sac filled with cerebrospinal fluid. Midbrain is usually not involved. Hydranencephaly is a relatively rare cerebral disorder. Differential diagnosis is mainly relevant when considering severe hydrocephalus, poroencephalic cyst and alobar holoprosencephaly. Ethical questions related to the correct criteria for the surgical treatment are also discussed. [ABSTRACT FROM AUTHOR]

The authors report a wide and updated revision of hydranencephaly, including a literature review, and present the case of a patient affected by this condition, still alive at 36 months. Hydranencephaly is an isolated and with a severe prognosis abnormality, affecting the cerebral mantle. In this condition, the cerebral hemispheres are completely or almost completely absent and are replaced by a membranous sac filled with cerebrospinal fluid. Midbrain is usually not involved. Hydranencephaly is a relatively rare cerebral disorder. Differential diagnosis is mainly relevant when considering severe hydrocephalus, poroencephalic cyst and alobar holoprosencephaly. Ethical questions related to the correct criteria for the surgical treatment are also discussed. [ABSTRACT FROM AUTHOR]

The current spectrum of disorders associated to clinical spasms with onset in infancy is wider than previously thought; accordingly, its terminology has changed. Nowadays, the term Infantile spasms syndrome ( ISs ) defines an epileptic syndrome occurring in children younger than 1 year (rarely older than 2 years), with clinical (epileptic: i.e., associated to an epileptiform EEG) spasms usually occurring in clusters whose most characteristic EEG finding is hypsarrhythmia [the spasms are often associated with developmental arrest or regression]. The term West syndrome ( WS ) refers to a form (a subset) of ISs, characterised by the combination of clustered spasms and hypsarrhythmia on an EEG and delayed brain development or regression [currently, it is no longer required that delayed development occur before the onset of spasms]. Less usually, spasms may occur singly rather than in clusters [ infantile spasms single-spasm variant ( ISSV )], hypsarrhythmia can be (incidentally) recorded without any evidence of clinical spasms [ hypsarrhythmia without infantile spasms ( HWIS )] or typical clinical spasms may manifest in absence of hypsarrhythmia [ infantile spasms without hypsarrhythmia (I SW) ]. There is a growing evidence that ISs and related phenotypes may result, besides from acquired events, from disturbances in key genetic pathways of brain development: specifically, in the gene regulatory network of GABAergic forebrain dorsal–ventral development, and abnormalities in molecules expressed at the synapse. Children with these genetic associations also have phenotypes beyond epilepsy, including dysmorphic features, autism, movement disorders and systemic malformations. The prognosis depends on: (a) the cause, which gives origin to the attacks (the complex malformation forms being more severe); (b) the EEG pattern(s); (c) the appearance of seizures prior to the spasms; and (d) the rapid response to treatment. Currently, the first-line treatment includes the adrenocorticotropic hormone ACTH and vigabatrin. In the near future the gold standard could be the development of new therapies that target specific pathways of pathogenesis. In this article we review the past and growing number of clinical, genetic, molecular and therapeutic discoveries on this expanding topic. [ABSTRACT FROM AUTHOR]

Background: In the past decades, the theory of 'allergen avoidance' was considered the standard treatment for preventing the onset of allergic diseases. Recently, the concept of 'immune tolerance' has replaced this old theory, and induction of tolerance by exposure is actually considered the appropriate method for preventing atopic diseases and other immunomediated pathologies. On the other hand, it is obvious that for public health reasons, abandoning current medical and hygienic practices is not desirable; therefore, safe alternatives, such as probiotics, have been suggested for providing necessary microbial stimulation. Objective: The purpose of our review is to describe the immunomodulatory and anti-inflammatory properties of probiotics, reporting literature data on their effect when used for the treatment of immunomediated diseases. Materials and methods: Articles reporting the evidence on the use of probiotics in immunomediated diseases, such as atopy, cow's milk allergy and rheumatoid arthritis (RA), and in inflammatory diseases, such as inflammatory bowel diseases (IBDs), with or without statistical meta-analysis, were selected in three different search engines: (1) MEDLINE via PubMed interface, (2) Scopus and (3) Google Scholar for all articles published from inception to July 2013. Titles and abstracts of identified papers were screened by two independent reviewers to determine whether they met the eligibility criteria of interest to develop our review. Subsequently, full texts of the remaining articles were independently retrieved for eligibility by the two reviewers. Results and Discussion: The recent literature is focusing its interest towards the immunologic properties of relatively harmless organisms, including lactobacilli and bifidobacteria, helminths and saprophytic mycobacteria that may skew immune responses towards immunoregulation by inducing Treg cells, rather than eliciting a pro-inflammatory immune response. For this reason, recent researches have been addressed on the use of probiotics to promote immunoregulation in atopic diseases, such as atopic/eczema dermatitis syndrome and food allergy, as well as in inflammatory-based diseases such as IBDs, RA and bronchial asthma. [ABSTRACT FROM AUTHOR]

Fibromatosis colli is an uncommon benign, congenital fibrous tumor or pseudotumor of the sternocleidomastoid muscle that manifests in infancy. In some of these patients tightening of the muscle results in torticollis. We report the case of a 3-week-old child, who presented with a neck mass localized in the left side with reduced mobility of the head. The diagnosis of fibromatosis colli was raised by ultrasound sonography. The mass regressed spontaneously within 3 months without surgical or physical treatment. [ABSTRACT FROM AUTHOR]

Asymmetric face flushing, known as harlequin syndrome, is an autonomic disorder that occurs with other dysfunctions or in isolation. It may be secondary to organic causes or unknown in origin. The latter, which is uncommon in childhood, is considered benign. We report on a boy who first showed this anomaly at 4 years of age, followed up for 6 years. During this time, we saw an increase in the frequency and duration of the episodes of asymmetric face flushing. In the past months, the episodes were associated with a wider involvement of autonomic symptoms, consisting of severe localized headache, lack of coordination, asymmetric sweating, and a loss of strength that lasted about 30 minutes. A review list of young patients affected by this condition is reported. [ABSTRACT FROM PUBLISHER]

Gelastic epilepsy are focal seizures manifesting as recurrent brief seizures starting as laughter or grimaces. They are most commonly associated with other types of seizures and can be secondary to infectious, malformative, metabolic, or neoplastic processes involving the central nervous system. We report on an 18-month-old girl who presented since the age of 2 months with multiple, recurrent, unprovoked episodes of stereotypical laughter. Brain magnetic resonance study revealed an hypothalamic hamartoma. Endoscopic tumor disconnection of the hamartoma resulted in rapid resolution of neurological symptomatology. [ABSTRACT FROM AUTHOR]

Psychogenic non-epileptic seizures (PNES) are defined as episodes of altered movements, sensations, and behaviours that resemble epileptic seizures but that are not associated with abnormal electrical brain discharges. The incidence of PNES in the general population is relatively low (about 1.5/100.000 persons per year), but the data from epilepsy centres show a much higher incidence rate. The identification of this pathological entity has significantly increased in the last years, also thanks to the setting-up of video-electroencephalography. The main challenge for physicians and neurologists is to distinguish PNES from epileptic seizures. The aim of this review was to analyse the clinical aspects and the diagnostic problems of PNES in epileptic patients in order to give practical advices for the identification of this problem and for distinguishing PNES from epileptic seizures. [ABSTRACT FROM AUTHOR]

Abstract: Ohtahara syndrome or Early Infantile Epileptic Encephalopathy (EIEE) with Suppression-Burst, is the most severe and the earliest developing age-related epileptic encephalopathy. Clinically, the syndrome is characterized by early onset tonic spasms associated with a severe and continuous pattern of burst activity. It is a debilitating and early progressive neurological disorder, resulting in intractable seizures and severe mental retardation. Specific mutations in at least four genes (whose protein products are essential in lower brain’s neuronal and interneuronal functions, including mitochondrial respiratory chains have been identified in unrelated individuals with EIEE and include: (a) the ARX (aristaless-related) homeobox gene at Xp22.13 (EIEE-1 variant); (b) the CDKL5 (SYK9) gene at Xp22 (EIEE-2 variant); (c) the SLC25A22 (GC1) gene at 11p15.5 (EIEE-3 variant); and (d) the Stxbp1 (MUNC18-1) gene at 9q34-1 (EIEE-4 variant). A yet unresolved issue involves the relationship between early myoclonic encephalopathy (EME–ErbB4 mutations) versus the EIEE spectrum of disorders. [Copyright &y& Elsevier]

The authors previously reported on the initial manifestations in a set of female twins, who presented soon after birth with bath-induced paroxysmal events each time they were immersed in a warm water bath. These episodes progressively ceased by the age of 36 months, replaced by paroxysmal episodes of alternating hemiplegia unrelated to water immersion. By age 4 years, the twins developed the classic features of alternating hemiplegia of childhood. Clinical outcomes at the age of 11 years are now reported. Standard and video-electroencephalograms showed a large, slow background activity followed by lower amplitude waves without focal abnormalities or other abnormal findings. This represents the first report on (a) alternating hemiplegia of childhood started with bath-induced paroxysmal episodes; (b) this condition in monozygotic twins; and (c) an 11-year follow-up study in which the twins continue to experience episodes of alternating hemiplegia in the setting of baseline cognitive impairment without epileptic episodes. [ABSTRACT FROM PUBLISHER]

Background: We report a study conducted in children and adolescents who are affected by primary headaches. The aim was to establish the most useful investigations for diagnosing headaches. Methods: The current study involved 300 consecutively hospitalized children and adolescents selected according to the criteria of the second edition of the International Classification of Headache Disorders. The following examinations were performed in all patients: full ophthalmologic; brain magnetic resonance imaging (MRI); electroencephalography; echocardiogram; and electrocardiogram. Dental, otorhinolaryngology, echocardiography of the supra-aortic trunks, abdominal ultrasound, and visual- and auditory-evoked potentials were carried out in patients according to the clinical signs associated with headache. Results: In a large number of cases routine laboratory analysis and neurophysiologic investigations were within the normal value when neurologic examination was normal. Electroencephalography, ophthalmologic studies and cerebral MRI are advisable as they can reveal precocious pathologic events, even in the absence of evident or alarming clinical signs. Conclusion: As widely reported in the literature, most of these investigations may be of little clinical value, but the authors reasoned that electroencephalography, ophthalmologic investigations and a cerebral MRI may be noteworthy because such studies may reveal a precocious pathologic event which can change the prognostic value of the headache. In addition, negative results on cerebral MRI may relieve the anxiety of parents and in turn may positively influence the clinical course of headache in children and adolescents. [ABSTRACT FROM AUTHOR]

The article presents a case study of dizygous twins with X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome in a wide clinical variability. Their parents are non-consanguineous, and had one healthy female child prior to the birth of the twins. The first twin was characterized with severe microcephaly based on his facial features. The second twin's facial anomalies are less present. Other factors beyond the ATR-X mutation are likely to play a complex role due to genetic variability.

Currarino syndrome (CS) is a peculiar form of caudal regression syndrome [also known as autosomal dominant sacral agenesis (OMIM no. 176450)] characterised by (1) partial absence of the sacrum with intact first sacral vertebra, (2) a pre-sacral mass and (3) anorectal anomalies ( Currarino triad). We studied a 3-year-old girl with Currarino triad who had additional systemic features and performed array comparative genomic hybridisation to look for chromosomal abnormalities. This girl had the typical spectrum of anomalies of the CS including (a) partial sacral agenesis (hemisacrum with remnants of only sacral S1–S2 vertebrae and a residual S3 vertebral body) associated with complete coccygeal agenesis, (b) pre-intrasacral dermoid, (c) intra-dural lipoma, (d) ectopic anus and (e) tethered cord. She had, in addition, pre- and post-natal growth impairment (<3rd percentile), severe microcephaly (<−3 SD) with normal gyration pattern and lack of cortical thickening associated with a hypoplastic inferior vermis, facial dysmorphism, sensorineural deafness and decreased serum levels of IGF-1. A de novo 10.3-Mb duplication of 7q34–q35 and an 8.8-Mb deletion on 7q36 were identified in this patient. The Homeobox HLXB9 (CS) gene is contained within the deletion accounting for the CS phenotype including microcephaly. The spectrums of associated abnormalities in the IGF-1 deficiency growth retardation with sensorineural deafness and mental retardation syndrome (OMIM no. 608747) are discussed. To the best of our knowledge, this is the first reported case of a patient with distal 7q chromosomal imbalance and features of CS triad (including microcephaly) and the first documented case of a patient with normal gyration pattern microcephaly. The spectrum of associated anomalies in this newly recognised phenotype complex consists of growth failure, typical facial anomalies with additional (previously unreported) nervous system abnormalities (e.g. sensorineural deafness) and somatomedin C deficiency. [ABSTRACT FROM AUTHOR]

Aims: The Atrophodermas include a large group of disorders appearing as localized or widespread depressed skin areas and characterized by underlying dermal atrophy. The present study aims to report a peculiar form of previously unreported focal dermal atrophy. Methods: We studied over a period of 5 years a boy who manifested, since birth, multiple hypopigmented cutaneous atrophic lesions of the atrophoderma type in a mosaic distribution over the body and the legs. Results: This boy did no develop other cutaneous or systemic stigmata except for an idiopathic thrombocytopenic purpura (ITP) manifested at age 2 years. Full serum, metabolic and infective analyses; full ophthalmological examination; ultrasound examination of the heart and internal organs; skeletal x-rays; brain magnetic resonance imaging; and DNA analysis of the PORCN ( Focal Dermal Hypoplasia - FDH) gene in this boy yielded normal results. Pathological analysis of multiple skin specimens from an affected area revealed slightly reduced dermal thickness; hyperpigmentation of the basal layer; homogenized and disarrayed collagen bundles; perivascular chronic infiltrates of lymphocytes and histiocytes; and normal skin appendages. Currently, the child is healthy; he has mildly improved skin status with less-evident skin depression throughout the lesion areas and no further complication has been recorded. The histological and clinical appearance of the skin lesions and the course were against any known disorder in the group of the atrophodermas. Conclusions: The cutaneous lesions seen in this boy represent a possibly new congenital skin disorder characterized by multiple, benign areas of focal dermal atrophy in a mosaic distribution. [ABSTRACT FROM AUTHOR]

Transient, recurrent or permanent causes of hydrocephalus in children are usually due to tumours, cerebral bleeding or colloid cysts and complications of infectious meningitis or secondary to poisoning. Recurrent, obstructive hydrocephalus is very rare. We report a 4-month-old boy who suffered at least three different episodes of obstructive hydrocephalus presumably caused by intermittent valvular blockage of the normal aqueduct cerebrospinal flow as indirectly demonstrated by serial standard and dynamic brain imaging studies. In addition, he had congenital left hydronephrosis secondary to congenital ureteropelvic junction stenosis. The child underwent an endoscopic third ventriculostomy with only transient post-surgical complications (i.e. central diabetes insipidus). The neurological symptoms rapidly improved after surgery, and the child is currently doing well with normal psychomotor development. [ABSTRACT FROM AUTHOR]

Stroke is a rare disorder in childhood; among its risk factors, C677T mutations in the methylenetetrahydrofolate reductase (MTHFR) gene with secondary hyperhomocysteinemia are considered. We report on a family in which two brothers had arterial ischemic stroke (AIS). One of these siblings came to our observation at the age of 4 years because of decreased motility of the right arm, mild hypotrophy of the right limbs, and frequent falls: brain magnetic resonance imaging revealed a large left AIS. Family history revealed that his older brother had died at the age of 7 due to AIS. An extensive metabolic investigation revealed a homozygous C677T [G80A-reduced folate carrier 1 (RFC1)] mutation in the MTHFR gene in both the affected siblings and in their healthy older brother and heterozygous mutations in the parents. None of these family members presented hyperhomocysteinemia. To the best of our knowledge, this is the first family with multiple AIS patients harboring homozygous MTHFR gene C677T (G80A-RFC1) mutations without associated hyperhomocysteinemia (the latter factor is usually considered as effector of vascular damage in patients with MTHFR C677T mutations). The pathogenic hypotheses of stroke in this family are considered. [ABSTRACT FROM AUTHOR]

Summary: We report on monozygotic twins with neonatal onset of daily reflex seizures triggered by hot water. Video record during the hot water bathing showed clinical signs consistent with a reflex seizure. The numbers of episodes were markedly reduced when the mother began bathing the children with reduced temperature bath water. At the age of 20 months, the twins developed episodes of paroxysmal disturbances including alternating hemiplegia. These two patients are the youngest reported cases of reflex hot water seizures, and the only reported cases in which reflex hot water seizures subsequently manifested episodes of alternating hemiplegia. [Copyright &y& Elsevier]

Recent infection seems to be an important and independent risk factor for neurological illness, but the mechanism linking infection and neurological involvement is still largely undetermined. Among infective agents, Mycoplasma pneumoniae is a reasonably common cause of neurological complications in childhood and it can manifest in several ways, including cerebral infarction and extrapyramidal features. Here, we report on a child who had a peripheral neuropathy chronologically, clinically and biologically related to M. pneumoniae infection. The present report supports the hypothesis of a close causal relationship between this infective agent and the neurological symptoms experienced by this child during an acute episode of respiratory disease. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging revealed numerous bilateral gadolinium-enhancing nodules, with perilesional edema and moderate midline shift (Fig A,B). The finding of cerebral aspergillosis lead to screening for the actual cause of her disease, the CGD, a primary phagocyte disorder resulting in increased risk of intracellular catalase-positive microorganism infections. Neuroaspergillosis, Chronic granulomatous disease, Brain, Inflammation, White matter involvement. [Extracted from the article]

Streptococcal infection in children is usually benign and self-limited. In a small percentage of children, prominent neurologic and/or psychiatric sequelae can occur. Sydenham chorea is the best defined and best recognized. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive-compulsive disorder consistently exacerbate in temporal correlation to a group A β-hemolytic streptococcal infection. PANDAS constitutes a subset of children with tics, Tourette syndrome, and obsessive-compulsive disorder. In addition to strictly defined PANDAS, we and others have recognized several PANDAS variants, including adult-onset variant, a dystonic variant, a myoclonic variant, and a ‘chronic’ PANDAS variant. The nosology and classification of these entities are rapidly evolving. The recognition that some pediatric neurobehavioral syndromes have infectious and/or immunologic triggers points to important new avenues of disease treatment. In this review, we summarize this complex and rapidly evolving area of clinical research. [ABSTRACT FROM AUTHOR]

Septo-optic dysplasia is defined by a variable combination of dysgenesis of midline brain structures including optic nerve hypoplasia and hypothalamic-pituitary dysfunction often associated with a wide variety of brain malformations of cortical development. Multiple congenital anomalies have been reported only sporadically. Despite recent demonstration of the possible pathogenic role of HESX1/Hesx1 gene (a homeobox gene important for development of prosencephalon), the etiology of most cases of septo-optic dysplasia still remains unclear. This report describes eight children (4 males, 4 females; age 2 to 17 years) with septo-optic dysplasia who manifested dysmorphic features (involving not only the midline facial structures) and a spectrum of additional clinical and imaging features including autism, facial hemangioma, and holoprosencephaly. Full mutational screening for the HESX1 gene in seven of eight children was negative. Based on the extreme variability of the clinical and imaging phenotypes hereby observed, on literature review, and on septo-optic dysplasia animal models, this study confirmed that the phenotypic heterogeneity in septo-optic dysplasia is high. We suggest that: (1) dysmorphic features are more frequent than previously thought—they may represent a relevant part of the phenotype; (2) septo-optic dysplasia should be recategorized as an heterogeneous malformation syndrome (septo-optic dysplasia complex) (encompassing multiple brain, endocrine, and systemic anomalies) rather than a single precisely defined entity. [Copyright &y& Elsevier]

This report describes a proband and his family consisting of 14 patients affected with simple congenital ptosis. Pedigree suggests an autosomal dominant pattern with 70-90% penetrance. The family includes patients with both unilateral and bilateral involvement, and cases with and/or without complex synkinesia. Left unilateral preponderance is striking, and pedigree analysis suggests the possibility of a modifier gene determining laterality. This study represents the first report of a large family with congenital autosomal dominant simple ptosis which demonstrates the full clinical spectrum of this condition. [Copyright &y& Elsevier]

Aim: To determine the frequency and clinical features of corpus callosum hypoagenesis, dysgenesis or hypoplasia in conjunction with extraparenchymal interhemispheric cyst.Methods: A retrospective study of clinical files and imaging records of all 2500 children referred to the University Department of Paediatrics, Catania, Italy, who underwent neuroimaging by ultrasound, computerized tomography or magnetic resonance imaging in 1992-2003. Five children (all girls, aged 2-18 y) were found to have abnormalities of the corpus callosum associated with interhemispheric cyst.Results: Three cases were type 2b, one type 2c and one mixed type 2b and 2c according to the classification proposed by Barkovich et al. The onset of clinical symptoms was very early, with severe neurological involvement, seizures that were difficult to treat and profound psychomotor retardation.Conclusions: In callosal anomalies with cysts, a prevalence in females is not confined to type 2b cysts, the spectrum of abnormalities of the corpus callosum is more varied than previously recorded, and the natural history and outcome of the condition are poor with profound developmental delay and drug-resistant seizures. The finding that all the cases were of type 2 suggests that the overall phenotype is more widespread than previously thought and may present in association with other complex syndromes. [ABSTRACT FROM AUTHOR]

Recently, an atypical form of celiac disease (CD) has been identified, in which gastrointestinal symptoms are less pronounced. Other organs can be more or less severely affected, and the disease might be unrecognized and undiagnosed. In some cases, hypertransaminasemia has been indicated as the first symptom of CD in infancy. A direct relationship between liver damage and glutensensitivity has been proven by the disappearance of biochemical signs and histological lesions of the liver after the initiation of the gluten-free diet. The present case report is of a 14-year-old girl affected by CD and severe hepatic failure who underwent a liver transplant. To our knowledge, this case is the first report of liver involvement related to CD which is so severe as to require a liver transplant in a child. Because most patients with CD remain undiagnosed, and, as observed in the present report, untreated CD with subclinical hepatic involvement can lead to more serious liver disease, a more aggressive diagnostic work-up for CD in the general population is warranted. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A β-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti–basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher''s exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection. [Copyright &y& Elsevier]