Behavioral Symptoms May Correlate With the Load and Spatial Location of Tubers and With Radial Migration Lines in Tuberous Sclerosis Complex

Objective: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous genetic disorder. The clinical manifestations are extensive and include neurological, dermatological, cardiac, ophthalmic, nephrological, and neuropsychiatric manifestations. The prediction and pathophysiology of neuropsychiatric disorders such as emotional symptoms, conduct problems, hyperactivity, and poor social behavior are poorly understood. The aim of the study was to diagnose neuropsychiatric symptoms in individuals with TSC, and to examine their possible correlations with quantity, magnitude, and spatial location of tubers and radial migration (RM) lines.Methods: The cohort comprised 16 individuals with TSC, aged 5–29 years, with normal or low normal intelligence. The participants or their parents were requested to fill Strengths and Difficulties Questionnaire (SDQ) and the TAND (TSC-associated neuropsychiatric disorders) Checklist for assessment of their neuropsychiatric symptoms. Correlations were examined between these symptoms and the magnitude, quantities, and locations of tubers and white matter RM lines, as identified in T2/FLAIR brain MRI scans.Results: The SDQ score for peer relationship problems showed correlation with the tuber load (r = 0.52, p < 0.05). Tuber load and learning difficulties correlated significantly in the temporal and parietal area. Mood swings correlated with tubers in the parietal area (r = 0.529, p < 0.05). RM lines in the temporal area correlated with abnormal total SDQ (r = 0.51, p < 0.05). Anxiety and extreme shyness were correlated with RM lines in the parietal area, r = 0.513, p < 0.05 and r = 0.593, p < 0.05, respectively. Hyperactive/inattention correlated negatively with RM lines in the parietal area (r = −707, p < 0.01).Conclusions: These observations may lead to future studies for precise localization of neuropsychiatric symptoms, thereby facilitating directed therapy.

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The Connectivity Fingerprint of the Fusiform Gyrus Captures the Risk of Developing Autism in Infants with Tuberous Sclerosis Complex

Cerebral Cortex ◽

10.1093/cercor/bhz233 ◽

2019 ◽

Vol 30 (4) ◽

pp. 2199-2214

Author(s):

Benoit Scherrer ◽

Anna K Prohl ◽

Maxime Taquet ◽

Kush Kapur ◽

Jurriaan M Peters ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Face Processing ◽

Genetic Disorder ◽

Neuropsychiatric Symptoms ◽

Autism Spectrum ◽

The Body ◽

Fusiform Gyrus ◽

Benign Tumors ◽

Anatomical Connectivity

Abstract Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.

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Multivariate Data Analysis Identifies Natural Clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND)

10.21203/rs.3.rs-835934/v1 ◽

2021 ◽

Author(s):

Petrus J de Vries ◽

Loren Leclezio ◽

Sugnet Gardner-Lubbe ◽

Darcy Krueger ◽

Mustafa Sahin ◽

...

Keyword(s):

Factor Analysis ◽

Tuberous Sclerosis ◽

Exploratory Factor Analysis ◽

Internal Consistency ◽

Tuberous Sclerosis Complex ◽

Genetic Disorder ◽

Neuropsychiatric Disorders ◽

Data Driven ◽

Small Scale ◽

Wide Range

Abstract BackgroundTuberous Sclerosis Complex (TSC), a multi-system genetic disorder, is associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND). Individuals have apparently unique TAND profiles, challenging diagnosis, psycho-education, and intervention planning. We proposed that identification of natural TAND clusters could lead to personalized identification and treatment of TAND. Two small-scale studies showed cluster and factor analysis could identify clinically meaningful natural TAND clusters. Here we set out to identify definitive natural TAND clusters in a large, international dataset.MethodCross-sectional, anonymized TAND Checklist data of 453 individuals with TSC were collected from six international sites. Data-driven methods were used to identify natural TAND clusters. Mean squared contingency coefficients were calculated to produce a correlation matrix, and various cluster analyses and exploratory factor analysis were examined. Statistical robustness of clusters was evaluated with 1000-fold bootstrapping, and internal consistency calculated with Cronbach’s alpha.ResultsWard’s method rendered seven natural TAND clusters with good robustness on bootstrapping. Cluster analysis showed significant convergence with an exploratory factor analysis solution, and, with the exception of one cluster, internal consistency of the emerging clusters was good to excellent. Clusters showed good clinical face validity.ConclusionsOur findings identified a data-driven set of natural TAND clusters from within highly variable TAND Checklist data. The seven natural TAND clusters could be used to train families and professionals and to develop tailored approaches to identification and treatment of TAND. Natural TAND clusters may also have differential aetiological underpinnings and responses to molecular and other treatments.

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Multivariate data analysis identifies natural clusters of Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND)

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-02076-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Petrus J. de Vries ◽

Loren Leclezio ◽

Sugnet Gardner-Lubbe ◽

Darcy Krueger ◽

Mustafa Sahin ◽

...

Keyword(s):

Factor Analysis ◽

Tuberous Sclerosis ◽

Exploratory Factor Analysis ◽

Internal Consistency ◽

Tuberous Sclerosis Complex ◽

Genetic Disorder ◽

Neuropsychiatric Disorders ◽

Data Driven ◽

Small Scale ◽

Wide Range

Abstract Background Tuberous Sclerosis Complex (TSC), a multi-system genetic disorder, is associated with a wide range of TSC-Associated Neuropsychiatric Disorders (TAND). Individuals have apparently unique TAND profiles, challenging diagnosis, psycho-education, and intervention planning. We proposed that identification of natural TAND clusters could lead to personalized identification and treatment of TAND. Two small-scale studies showed cluster and factor analysis could identify clinically meaningful natural TAND clusters. Here we set out to identify definitive natural TAND clusters in a large, international dataset. Method Cross-sectional, anonymized TAND Checklist data of 453 individuals with TSC were collected from six international sites. Data-driven methods were used to identify natural TAND clusters. Mean squared contingency coefficients were calculated to produce a correlation matrix, and various cluster analyses and exploratory factor analysis were examined. Statistical robustness of clusters was evaluated with 1000-fold bootstrapping, and internal consistency calculated with Cronbach’s alpha. Results Ward’s method rendered seven natural TAND clusters with good robustness on bootstrapping. Cluster analysis showed significant convergence with an exploratory factor analysis solution, and, with the exception of one cluster, internal consistency of the emerging clusters was good to excellent. Clusters showed good clinical face validity. Conclusions Our findings identified a data-driven set of natural TAND clusters from within highly variable TAND Checklist data. The seven natural TAND clusters could be used to train families and professionals and to develop tailored approaches to identification and treatment of TAND. Natural TAND clusters may also have differential aetiological underpinnings and responses to molecular and other treatments.

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TUBEROUS SCLEROSIS: PRESENTATION OF A CASE AND REVIEW OF THE LITERATURE

10.36106/gjra/4910349 ◽

2021 ◽

pp. 95-96

Author(s):

Fabricio Andrés Lasso Andrade ◽

Jorge Alejandro Cadena Arteaga ◽

Ángela Maria Fajardo Arteaga ◽

Viviana Lizeth Echeverry Morillo ◽

David Alfredo Acevedo Vargas ◽

...

Keyword(s):

Nervous System ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Autosomal Dominant ◽

Genetic Disorder ◽

Causal Link ◽

Benign Tumors ◽

Review Of The Literature ◽

Dominant Inheritance ◽

Variable Expression

Tuberous Sclerosis Complex (TSC) also known as Bournneville disease. TSC is a multisystemic genetic disorder with autosomal dominant inheritance, of variable expression, which is mainly characterized by the presence of benign tumors or hamartomas in the nervous system and skin, but which may also be present in the heart, kidney, lung and other organs. The most frequent symptom is epilepsy, affecting 80-90% of patients with TSC which manifests itself in childhood between 1 to 3 years of age. We present a case of sporadic onset tuberous sclerosis with epilepsy that had a causal link with TSC after admission to the emergency room in a convulsive status.

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Brain MRI in Fetuses with Cardiac Tumours

The Neuroradiology Journal ◽

10.1177/197140090702000503 ◽

2007 ◽

Vol 20 (5) ◽

pp. 494-499 ◽

Cited By ~ 3

Author(s):

E. Jurkiewicz ◽

M. Bekiesińska-Figatowska ◽

A. Romaniuk-Doroszewska ◽

J. Dangel

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Imaging Modality ◽

Brain Mri ◽

Multisystem Disorder ◽

Complete Evaluation ◽

Sonographic Examination ◽

Diagnosis And Prognosis ◽

Prenatal Mri ◽

Cardiac Tumours

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder which affects the skin, brain, heart and other organs. It is caused by mutations of two genes: TSC1 (on chromosome 9q34) or TSC2 (on 16p13.3). 70% of cases are sporadic with new mutations. This study aimed to highlight the utility of prenatal MRI as an adjunct imaging modality in the diagnosis and prognosis of tuberous sclerosis complex. Prenatal ultrasound and magnetic resonance imaging were performed in seven fetuses at a gestational age of 30, 32, 34 and 35 weeks using a 1.5 T MRI scanner. SSFSE,T2- and FGRE/T1-weighted images were obtained in axial, coronal and sagittal planes. Postnatal MRI was performed in two cases. Intracardiac tumors (rhabdomyomas) were revealed on ultrasound in all fetuses. On sonographic examination the brain tissue appeared normal in all cases. Brain MRI revealed focal low-signal-intensity lesions, localized along the walls of the lateral ventricles of five fetuses. Another hypointense lesion was seen at the grey/white matter junction in one case. Brain MRI of two fetuses was normal. The diagnosis of TSC was established in five cases. Postnatal MRI in two cases confirmed prenatal findings. MRI allows more complete evaluation of the fetus and helps to determine the diagnosis and prognosis in cases of TSC. The use of prenatal MR imaging in addition to prenatal sonography has the potential to improve genetic counseling and prenatal diagnosis of patients with tuberous sclerosis.

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Tuberous sclerosis complex renal disease

10.1093/med/9780199592548.003.0330 ◽

2015 ◽

Cited By ~ 1

Author(s):

Bradley P. Dixon ◽

J. Christopher Kingswood ◽

John J. Bissler

Keyword(s):

Renal Failure ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Autosomal Dominant ◽

Genetic Disorder ◽

Mammalian Target Of Rapamycin ◽

Cystic Disease ◽

Pulmonary Lymphangioleiomyomatosis ◽

Brain Involvement ◽

Almost All

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting almost all organs. It has wider phenotypic variation than often appreciated, with less than half showing the combination of characteristic facial angiofibromas, epilepsy, and mental retardation. Renal angiomyolipomata or cysts are found in 90% and renal failure was historically a common mode of adult death from the disease. Pulmonary lymphangioleiomyomatosis is restricted to females. Angiomyolipomata or cystic disease, or both, may cause renal failure. Angiomyolipomata may also haemorrhage, especially from larger lesions. Manifestations of brain involvement substantially complicate management of many patients with TSC. The causative genes TSC1 and TSC2 encode tuberin and hamartin which are involved in control of the mammalian target of rapamycin pathway. Inhibitors of that pathway, such as sirolimus and everolimus, are therefore logical approaches to therapy and have been shown to be effective in reducing angiomyolipomata volume. It remains to be seen whether they can protect renal function.

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Description of a multidisciplinary model of care in a French cohort of adult patients with tuberous sclerosis complex

Journal of Medical Genetics ◽

10.1136/jmedgenet-2019-106607 ◽

2020 ◽

Vol 58 (1) ◽

pp. 25-31

Author(s):

Pierre Pfirmann ◽

Jerome Aupy ◽

Eva Jambon ◽

Laetitia Idier ◽

Mathilde Prezelin-Reydit ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Multidisciplinary Approach ◽

Genetic Disorder ◽

Multidisciplinary Care ◽

Adult Patients ◽

Bone Lesions ◽

Interdisciplinary Management ◽

Cutaneous Lesions ◽

High Level

BackgroundTuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Due to the various manifestations of TSC and their potential complications, a multidisciplinary care approach is recommended by consensus guidelines.ObjectivesOur study aimed to give a complete description of our TSC adult cohort and to evaluate the multidisciplinary and interdisciplinary management model.MethodsData on each adult patient diagnosed with TSC, including disease manifestations, interventions and outcomes, were collected at baseline and updated annually. A multidisciplinary TSC approach with all the recommended explorations was carried out annually.Results90 patients were enrolled in Centre Hospitalier Universitaire de Bordeaux, between January 2000 and September 2018. Median age of patients at inclusion was 37 years (range, 27–47) and 20 years old at diagnosis of TSC. Regarding the occurrence of TSC manifestations, 97% of the patients had cutaneous lesions, 89% had neurological manifestations, 83% had renal manifestations and 100% had dental lesions with pits. More than half the patients had sclerotic bone lesions (68%), TSC-associated neuropsychiatric disorders (64%) and lymphangioleiomyomatosis (59%). A TSC multidisciplinary approach was developed including a global follow-up and an evaluation of TSC targeting organs, according to the recommendations. A satisfaction survey revealed global and entire satisfaction of patients with TSC.ConclusionWe obtained an accurate description of a cohort of adult patients with TSC. Our multidisciplinary approach model allowed us to provide optimal management of patients with TSC with a high level of patient satisfaction.

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Fetal Echocardiographic Detection of Cardiac Tumors: A Case Report of Multiple Fetal Cardiac Rhabdomyomas

Journal of Diagnostic Medical Sonography ◽

10.1177/8756479319847641 ◽

2019 ◽

Vol 35 (5) ◽

pp. 426-430

Author(s):

Bailey Sarff ◽

Randall Floyd ◽

Amy Bildner ◽

Janell Stormo ◽

Kelsy Fisher

Keyword(s):

Case Report ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Cardiac Tumor ◽

Genetic Disorder ◽

Cardiac Tumors ◽

Size Number

Cardiac rhabdomyomas are the most common fetal cardiac tumor. They can be detected in the second and third trimesters. Rhabdomyomas are most commonly associated with the genetic disorder tuberous sclerosis complex. When associated with tuberous sclerosis complex, cardiac rhabdomyomas usually regress within the first few years of life, without complications. Symptoms depend on the size, number, and location of the rhabdomyomas. A case report of multiple cardiac rhabdomyomas that was found at 35 weeks’ gestation and is discussed.

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