Diagnosis of tuberous sclerosis complex in the fetus Dragoumi, Pinelopi; O’Callaghan, Finbar; Zafeiriou, Dimitrios I.
European journal of paediatric neurology,
November 2018, 2018-Nov, 2018-11-00, 20181101, Letnik:
22, Številka:
6
Journal Article
Recenzirano
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Tuberous sclerosis complex is a dominantly inherited genetic disorder of striking clinical variability. It is caused by mutations in either TSC1 or TSC2 gene, which regulate cell growth and ...proliferation by inhibition of mTORC1 signaling. TS is characterized by the development of benign tumors in many tissues and organs and its neurological manifestations include epilepsy, autism, cognitive and behavioral dysfunction, and giant cell tumors. With mechanism-based mTOR inhibitors therapy now available for many of its manifestations, early diagnosis of TSC is very important in order to offer appropriate care, long-term surveillance and parental counseling. Fetal ultrasound and MRI imaging techniques have evolved and may capture even earlier the following TSC-associated lesions: cardiac rhabdomyomas, subependymal nodules, cortical tubers and renal cysts. Often these represent an incidental finding during a routine ultrasound. Furthermore, in the past decades prenatal molecular diagnosis of TSC has emerged as an important option for families with a known affected member; however, the existing evidence with regards to the clinical characteristics and long-term outcome of babies diagnosed prenatally with TSC is yet limited and the path that follows early TSC detection merits further research.
•Early diagnosis of TSC is very important in order to offer appropriate care.•Advanced fetal imaging techniques may capture TSC-associated lesions earlier.•Prenatal molecular diagnosis of TSC has emerged as an important option for families.•Long-term outcome of prenatally diagnosed TSC is not clear.•The role of presymptomatic treatment in TSC is a topic of ongoing research.
Hemimegalencephaly is a rare malformation of cortical development characterised by enlargement of one cerebral hemisphere. The association between hemimegalencephaly and tuberous sclerosis complex, ...an autosomal dominant genetic disorder, is uncommon and has so far been reported only in a few cases. Intractable epilepsy and severe developmental delay are typical clinical manifestations. Aberrant activation of the mTOR signalling pathway is considered to be the hallmark of the pathogenesis of these two disorders. Thus, mTOR inhibitors such as everolimus represent a promising therapeutic approach to mTOR-associated manifestations. We present a thorough literature review of the association between hemimegaloencephaly and tuberous sclerosis complex.
•TSC can be rarely associated with malformations of cortical development such as HME.•Ongoing surveillance of patients with HME for features of TSC is highly recommended.•Everolimus could be a potential therapeutic approach in mTORopathies with drug-resistant epilepsy and neurodevelopmental regression.
Autism is a heterogeneous neurodevelopmental disorder with a variety of different etiologies, but with a heritability estimate of more than 90%. Although the strong correlation between autism and ...genetic factors has been long established, the exact genetic background of autism is still unclear. This review refers to all the genetic syndromes that have been described in children with pervasive developmental disorders (tuberous sclerosis, fragile X, Down, neurofibromatosis, Angelman, Prader-Willi, Gilles de la Tourette, Williams, etc.). Issues covered include prevalence and main characteristics of each syndrome, as well as the possible base of its association with autism in terms of contribution to the current knowledge on the etiology and genetic base of pervasive developmental disorders.
Background Sickle cell disease (SCD) is associated with an increased risk of cardiovascular disease that may be due to a variety of possible risk factors, including abnormal blood pressure. Blood ...pressure (BP) of children and adolescents with SCD has been reported to be lower compared to the BP of the general pediatric population. Methods To confirm this prior observation, we compared reference BP values for children with SCD with reference BP values of the general pediatric population. We hypothesized that children with SCD do not have lower BPs than children without SCD. Results Systolic BP differed for both males and females, over the different age groups between pediatric subjects with and without SCD. Systolic BP was higher in children with SCD, in both obese and non-obese populations. Diastolic BP did not differ between the groups. Conclusions Our analysis demonstrated that systolic BP values are indeed higher in children with SCD than in the general pediatric population. This finding is consistent with the most recent literature showing abnormal BP patterns in the SCD pediatric population utilizing 24-hour BP monitoring devices. This is an important step for recognizing abnormal BP as a risk factor for cardio- and neurovascular events in SCD. Keywords: Pediatric hematology/oncology, Sickle cell Anemia, Hypertension, Systolic, Childhood, Pediatrics
The branched-chain amino acid (BCAA) is a group of essential amino acids that are involved in maintaining the energy balance of a human being as well as the homoeostasis of GABAergic, glutamatergic, ...serotonergic and dopaminergic systems. Disruption of these systems has been associated with the pathophysiology of autism while low levels of these amino acids have been discovered in patients with autism. A pilot open-label, prospective, follow-up study of the use of BCAA in children with autistic behaviour was carried out. Fifty-five children between the ages of 6 and 18 participated in the study from May 2015 to May 2018. We used a carbohydrate-free BCAA-powdered mixture containing 45·5 g of leucine, 30 g of isoleucine and 24·5 g of valine in a daily dose of 0·4 g/kg of body weight which was administered every morning. Following the initiation of BCAA administration, children were submitted to a monthly psychological examination. Beyond the 4-week mark, BCAA were given to thirty-two people (58·18 %). Six of them (10·9 %) discontinued after 4-10 weeks owing to lack of improvement. The remaining twenty-six children (47·27 %) who took BCAA for longer than 10 weeks displayed improved social behaviour and interactions, as well as improvements in their speech, cooperation, stereotypy and, principally, their hyperactivity. There were no adverse reactions reported during the course of the treatment. Although these data are preliminary, there is some evidence that BCAA could be used as adjunctive treatment to conventional therapeutic methods for the management of autism.
The neurodevelopmental impairment in tuberous sclerosis complex (TSC) has a multifactorial origin. Various factors have been proposed as predictors of neurological outcome such as tuber load, seizure ...onset, and TSC2 mutation. Cerebellar lesions have been associated with worse neuroradiological phenotype, but their contribution is not well understood.
A partly retrospective and partly prospective pediatric cohort study was conducted at three hospitals in Greece between 2015 and 2020. Patients aged ≤ 18 years with a confirmed TSC daignosis were included and underwent brain imaging, a semistructured interview (authorized Greek version of the tuberous sclerosis-associated neuropsychiatric disorders, or TAND, checklist), and intellectual ability assessment.
The study populations consisted of 45 patients with TSC (22 females, 23 males; mean age 9.53 years). Twenty patients (44.4%) had cerebellar lesions. Cerebellar involvement was the most powerful predictor of tuber load (P = 0.03). Cerebellar lesions were associated with giant cell astrocytomas (SEGAs) (P = 0.01) and severe neurological outcome (P = 0.01). Even though in the univariate analysis early seizure onset, tuber load, and cerebellar involvement were associated with intellectual impairment and neurological severity, none of them was an independent predictor of cognitive outcome and neurological severity.
Cerebellar lesions are common among individuals with TSC. Cerebellar involvement correlates with supratentorial derangement and the development of SEGAs, which is suggestive of a more severe clinical and neuroradiological phenotype. Cerebellar involvement and early seizure onset were not independent predictors of either neurological severity or intellectual disability or neurobehavioral outcome; their role in TSC clinical phenotype should be further investigated.
Nephrotic syndrome (NS) in childhood can be accompanied by serious neurological complications increasing the morbidity of disease. The study aimed to assess the spectrum of neurological complications ...in children with in terms of clinical presentation, contributory risk factors, and outcome.
In this systematic review, we searched for articles in PubMed, providing individual patient-level data for any neurological complication in children and adolescents with primary NS, between January 1, 1990 and April 30, 2018.
The search yielded 63 articles, involving 103 patients. Events occurred more frequently during nephrotic state relapses; 71.6% of cerebral thromboembolic (TE) events and 81.2% of posterior reversible encephalopathy (PRES) cases. Median duration of disease before a cerebral TE event was 3 months (IQR 0–27), and 18 months (IQR 1-37.5) for PRES. Among cases with TE, 73.1% presented with cerebral sinovenous thrombosis (CSVT), and 16.9% parenchymal lesions. 70% of patients had a risk factor for neurological complication including NS-associated thrombophilia, hypertension, and treatment with immunosuppressive agents. Outcome was favorable in 93.8% of the patients with PRES. In patients with cerebral TE outcome was favorable in 95.8% of the cases with CSVT only, and in 64.7% of the cases with parenchymal lesions.
Neurological complications may occur in children with primary NS and risk factors during nephrotic state relapses. The outcome for PRES has been reported favorable. Outcome in cerebral TE events may differ by the presence of venous or artery infarct. Recognition of additional protrombotic state risk factors may help to lower the incidence of neurological complications.
•Neurological complications occurred frequently during nephrotic state relapses in patients with risk factors.•Outcome is usually favorable, but neurological sequelae are common in cases with arterial stroke.•Nephrotic state needs further research to identify biomarkers for the risk of disease-associated neurological morbidity.
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