Ataxia in children: early recognition and clinical evaluation

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

The role of puberty and adolescence in the pathobiology of pediatric multiple sclerosis

Abstract Multiple sclerosis (MS) is increasingly recognized in the paediatric age. In a smaller, but well-established, proportion of paediatric MS patients [20% of total paediatric MS cases: 0.2% to 0.7% of the total MS patients] the onset of disease is before 10 years of age [pre-pubescent (childhood) MS]; in the majority [80%] of paediatric MS patients, however [1.7% to 5.6% of the total MS population], the onset of disease is between 10 and 18 years [post-pubertal (juvenile) MS]. Notably, while pre-pubertal MS occurs almost equally in both genders (female/male ratio = 0.9:1; reverting to 0.4–0.6/1 in pre-school MS children) the female/male ratio rises to 2.2/3:1 in the post-pubertal age. Interestingly, precocious puberty has been associated to: (a) a higher risk of developing MS; and (b) a more severe disease course. In addition to that, males are more susceptible to MS (and manifest more neurodegeneration) than females the latter being however more inflammatory than males; pregnancy however reduces MS relapses. All the above findings led to the suggestion of an underlying female sex hormonal involvement in the pathophysiology of MS vs. a protective role of male sex hormones. Epigenetic perspectives indicate that the interplay between genetic background, environmental triggers and neuroendocrine changes, typically occurring around the time of adolescence, could all play a combined role in initiating and/or promoting MS with onset in the paediatric age including many of the most frequent disease-associated risk factors (e.g., overweight/obesity, low vitamin D levels, reduced sunlight exposure, Epstein-Barr virus infection). According to this proposed complex multifactorial model, susceptibility to MS may be thus acquired during pre-pubertal age and children have probably to wait until the adolescence to manifest their first clinical signs/symptoms

Acute deep vein thrombosis (DVT) of the lower limbs in a 32-year-old man with chronic hypoplasia of the inferior vena cava (HIVC) without risk factors

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Cervical neurenteric cyst and Klippel-Feil syndrome: An abrupt onset of myelopathic signs in a young patient

Neurenteric cysts (NECs), also called enterogenous cysts or enterogenic cysts, are congenital malformative anomalies of endodermal origin that manifest with a variety of disorders, including spine anomalies. Neurenteric cysts are uncommon developmental disorders reported in 0.7%–1.3% of all spinal tumors. Klippel-Feil syndrome (KFS) defines a malformative spine disorder presenting with congenital fusion of cervical vertebrae and/or other parts of the spine. In patients with KFS, NECs are rarely reported; they may be silent for long periods of time, showing a slow progressive course or manifesting with an acute, severe neurological presentation or with fluctuating myelopathic symptoms. We report a young patient affected by KFS associated with a NEC which, in a short period of time, progressively caused myelopathic symptomatology. Surgical intervention resulted in resolution of the neurological signs. Keywords: Neurenteric cyst, Klippel-Feil syndrome, Intramedullary cys

Intronic Variant in CNTNAP2 Gene in a Boy With Remarkable Conduct Disorder, Minor Facial Features, Mild Intellectual Disability, and Seizures

Introduction: Mutations in the contactin-associated protein-like 2 (CNTNAP2) gene (MIM#604569) encoding for CASPR2, a cell adhesion protein of the neurexin family, are known to be associated with autism, intellectual disability, and other neuropsychiatric disorders. A set of intronic deletions of CNTNAP2 gene has also been suggested to have a causative role in individuals with a wide phenotypic spectrum, including Pitt-Hopkins syndrome, cortical dysplasia-focal epilepsy syndrome, Tourette syndrome, language dysfunction, and abnormal behavioral manifestations. Case presentation: A 10-years-old boy was referred to the hospital with mild intellectual disability and language impairment. Moreover, the child exhibited minor facial features, epileptic seizures, and notable behavioral abnormalities including impulsivity, aggressivity, and hyperactivity suggestive of the diagnosis of disruptive, impulse-control and conduct disorder (CD). Array comparative genomic hybridization (CGH) revealed a copy number variant (CNV) deletion in the first intron of CNTNAP2 gene inherited from a healthy father. Conclusions: A comprehensive description of the phenotypic features of the child is provided, revealing a distinct and remarkable alteration of social behavior not previously reported in individuals affected by disorders related to CNTNAP2 gene disruptions. A possible causative link between the deletion of a non-coding regulatory region and the symptoms presented by the boy has been advanced

Clinical and Pharmacological Aspects of Inflammatory Demyelinating Diseases in Childhood: An Update

Inflammatory demyelinating diseases comprise a spectrum of disorders affecting the myelin of the central and peripheral nervous system. These diseases can usually be differentiated on the basis of clinical, radiological, laboratory and pathological findings

Case report: A gain-of-function of hamartin may lead to a distinct “inverse TSC1-hamartin” phenotype characterized by reduced cell growth

Mutations of TSC1 and TSC2 genes cause classical Tuberous Sclerosis Complex (TSC), a neurocutaneous disorder characterized by a tendency to develop hamartias, hamartomas, and other tumors. We herein report on a girl, now aged 5 years, who presented a previously unreported, distinct clinical phenotype consisting of primary microcephaly (head circumference = 40 cm, −5.6 standard deviations), brain anomalies including hypoplasia of the corpus callosum (with a residual draft of the genu), simplified parieto-temporal gyral pattern, colpocephaly with ectasia of the temporal ventricular horns, intellectual disability, and a general pattern of reduced growth (with weight and height < 3rd centiles). No classical features of TSC were recorded; the girl harbored a novel missense variant in TSC1 (c.611G > A). We hypothesize that her clinical phenotype could be related to a “gain-of-function” of the TSC1 protein product hamartin, causing an increase in the effects of the protein on inhibition of its intracellular targets (i.e., mTORC or RAC1 pathways), resulting in a distinct “inverse TSC1-hamartin” phenotype characterized by reduced growth of cells instead of the more classical predisposition to increased cell growth

Chromosome 15q BP3 to BP5 deletion is a likely locus for speech delay and language impairment: Report on a four-member family and an unrelated boy

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