Case Of Tuberous Sclerosis Complex Research Articles

Tuberous Sclerosis Complex in a 20-year-old Female: Delayed Recognition and Life-threatening Outcomes

Tuberous sclerosis complex (TSC) is a rare, autosomal dominant multisystem disorder affecting the brain, heart, kidneys, lungs, and skin leading to significant morbidity and mortality. We report a case of TSC and highlight the need for prompt diagnosis and proper surveillance to minimize life-threatening complications. A 20-year-old female presented with facial and ungual papulonodular lesions 4 years after being diagnosed with epilepsy at the age of eight. No family history of genetic diseases was reported. Eight years later, the patient developed recurrent cough, shortness of breath, and blurring of vision. Biopsy of facial and digital nodule showed angiofibroma and ungual fibroma (Koenen tumor), respectively. Chest computed tomography scan revealed extensive cystic lesions diffusely scattered throughout the entire lung parenchyma suggestive of lymphangioleiomyomatosis. Cranial MRI revealed cortical and subependymal tubers, compatible with TSC. The patient had multidisciplinary management. However, her symptoms progressed, and she eventually succumbed to death. Cutaneous lesions such as facial angiofibromas and ungual fibromas along with multisystemic manifestations should alarm the clinician to TSC. Given its highly variable expressivity, awareness of different TSC-associated signs and symptoms is essential for prompt diagnosis, proper treatment, disease monitoring, and early recognition of TSC complications.

Isolated Renal Multifocal Epithelioid Angiomyolipoma Leading to Non-Functioning Kidney in a Case of Tuberous Sclerosis Complex with Piebaldism

A 19-year-old gentleman presented to the outpatient department with chief complaint of a right loin mass which had been increasing in size since the past 1 year and had been insidious in onset, causing right loin pain, discomfort, early satiety, along with loss of weight and loss of appetite. Patient was a known case of tuberous sclerosis complex with piebaldism since childhood and had related clinical features like Ash-leaf macules on the trunk, retinal hamartomas along with a recurrent intra-oral disfiguring hamartoma (histopathologically proven acanthosis with hyperkeratosis).

Tuberous Sclerosis Complex: Clinical Case Presentation and Literature Review

Tuberous sclerosis complex is a rare congenital illness with autosomal dominant transmission caused by a mutation in the TSC1 or TSC2 gene. It belongs to the phacomatoses and is distinguished by multi-systemic manifestations that can cause neurological, dermatological, cardiovascular, renal, ocular, pulmonary, renal, ocular, pulmonary, endocrine, gastrointestinal, and bone abnormalities. Here, we detail a familial case of tuberous sclerosis complex clinically diagnosed, along with the importance of early clinical, genetic diagnosis and therapy . Keywords: Tuberous sclerosis complex, Genetic disorder, Multisystemic disease, Epilepsy, Case report.

Topical sirolimus for the treatment of facial angiofibromas in tuberous sclerosis patient: a case report

<p class="abstract">Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder seen in 1/6000 births. Facial angiofibroma is the most common cosmetic disfiguring cutaneous manifestation of it. Therapeutic modalities include cryotherapy, podophyllotoxin application, electrocoagulation, surgery and laser therapy associated with their own high risk of complications and sequelae. Sirolimus is a lipophilic lactone isolated from <em>Streptomyces hygroscopicus</em> (soil bacteria), found to have anti-T-cell properties and classifies as an anticancer drug from the mammalian target of rapamycin (mTOR) inhibitors. Sirolimus binds with mTOR and causes inhibition of mTOR activity and VEGF‑stimulated endothelial cell proliferation. Topical preparation produced by crushing tablets of sirolimus 1 mcg and mixing in an aqueous base emollient or the solution form of sirolimus has been used with beneficial effects in the treatment of angiofibroma, especially in younger patients. Here we reported a case of a 34-year-old male, a known case of TSC with facial angiofibroma in which the topical 0.1% sirolimus had been used with beneficial effects and clinical outcomes.</p><p class="abstract"> </p>

The Peculiar Case Of Diplopia

A nineteen - year - old female presented with a history of binocular diplopia for one week. She had a history of headache, seizures, and memory loss. Magnetic Resonance Imaging (MRI) of brain revealed subependymal astrocytoma as the cause of her symptoms. Our pa tient was a probable case of tuberous sclerosis complex (TSC). Diplopia was the presenting sign in this case diagnosis.

A case report of severe tuberous sclerosis complex detected in utero and linked to a novel duplication in the TSC2 gene

BackgroundDisease severity is tremendously variable in tuberous sclerosis complex (TSC). In contrast with the detailed guidelines available for TSC diagnosis and management, clinical practice lacks adequate tools to evaluate the prognosis, especially in the case of in utero diagnosis. In addition, the correlation between genotypes and phenotypes remains a challenge, in part due to the large number of mutations linked to TSC. In this report, we describe a case of severe TSC diagnosed in utero and associated with a specific mutation in the gene tuberous sclerosis complex 2 (TSC2).Case presentationA mother was referred for a thorough investigation following the observation by ultrasound of cardiac abnormalities in her fetus. The mother was healthy and reported frequent, intense and long-lasting hiccups/spasms in the fetus. The fetus of gestational age 33 weeks and 4 days was found to have multiple cardiac tumors with cardiac ultrasound. Brain magnetic resonance imaging (MRI) performed in utero revealed the presence of sub-ependymal nodules and of abnormal signals disseminated in the white matter, in the cerebral cortex and in the cerebellum. Following diagnosis of definite TSC, pregnancy interruption was chosen by the parents. Genetic testing of the fetus exposed a duplication in exon 41 of TSC2 (c.5169dupA), which was absent in the parents. The autopsy ascertained the high severity of brain damage characterized by an extensive disorganisation of white and grey matter in most cerebral lobes.ConclusionsThis case presentation is the first to depict the association between a de novo TSC2 c.5169dupA and multi-organ manifestation together with indications of a particularly high disease severity. This report can help physicians to perform early clinical diagnosis of TSC and to evaluate the prognosis.

Tuberous Sclerosis Complex Associated Lymphangioleiomyomatosis Presenting with Spontaneous Pneumothorax and Renal Angiomyolipomas

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder manifested by involvement of multisystem including skin, central nervous system, heart, kidneys and eyes. Lymphangioleiomyomatosis (LAM) is also a multisystem disorder that primarily affects the lungs. We report a case of tuberous sclerosis complex associated lymphangio-leiomyomatosis (TSC-LAM) in a 26-year-old female patient who was presented with spontaneous pneumothorax and renal angiomyolipomas. In clinical examination; We found multiple angiofibromas over her face, shagreen patches over upper and lower back and ungual fibromas in both fingers and toes. HRCT of chest revealed right sided pneumothorax with multiple thin walled cysts in both lungs. Ultrasonogram (USG) and Computer Tomography (CT) scan of abdomen revealed bilateral angiomyolipomas. We managed her pneumothorax with intercostal chest tube drainage and oxygen inhalation.
 Bangladesh Med J. 2019 May; 48 (2): 51-54

Novel small molecule protein kinase CK2 inhibitors exert potent antitumor effects on T98G and SEGA cells in vitro.

Tumours of astroglial origin, both malignant glioblastoma (GBM) and benign subependymal giant cell astrocytoma (SEGA), pose a serious medical problem. Casein kinase 2 (CK2), a member of the serine/threonine kinase family, has antiapoptotic properties and plays a vital role in glial tumour cell survival. It contributes to invasive cell growth and is often upregulated in malignant neoplastic cells; however, its role in benign tumours of astrocytic origin is less understood. In the present study we investigated the effects of small molecule CK2 inhibitors on proliferation and viability of glioma cells in vitro. The experiments were conducted on commercial T98G malignant glioma cell line and the SEGA cell line, derived from a paediatric case of tuberous sclerosis complex (TSC). Cell cultures were incubated with selected CK2 inhibitors: 4,5,6,7-tetrabromo-1H-benzimidazole (TBI), 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBB) at 0.1, 1, 10, 25, 50, 75 and 100 µM concentrations for 24 and 48 hours. Cell proliferation was assessed using a cell counter and cell viability was evaluated by MTT assay. TBB at 75 µM and 100 µM, and TBI starting from 25 µM, both reduced T98G cell proliferation after 24 hours, while DMAT was ineffective. All tested small molecule CK2 inhibitors appear to reduce T98G cell growth and viability after 48 hours, although TBI appeared to be the most effective and reduced cell growth in the 50-100 µM dose range. TBI also showed potential efficacy in reducing the number and viability of SEGA cells after 48 hours. Proliferation and viability of SEGA cells have proven resistant to TBB treatment. DMAT only reduced the viability of SEGA cells at 24 (at 100 µM) and 48 hours (10-100 µM). Importantly, normal human astrocyte cells were found to be moderately resistant to TBB, while their viability was mildly reduced at higher doses of DMAT and TBI. In conclusion, CK2 appears to play a role not only in malignant glioma cells but it can also sustain the viability and proliferation of benign astrocytoma cells. The obtained antitumor effects of CK2 inhibitors significantly exceeded their mild or no effect on normal astrocytes in control, which supports the therapeutic potential of these compounds against gliomas.

A case of tuberous sclerosis complex masquerading as Birt-Hogg-Dube syndrome

A case of tuberous sclerosis complex masquerading as Birt-Hogg-Dube syndrome

Oral lesions in tuberous sclerosis

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous syndrome with an approximate incidence of 1 in 10,000–50,000. The cardinal features of TSC are skin lesions, convulsive seizures, and mental retardation. Here, we report a case of TSC in a male patient who presented with oral and cutaneous manifestations without mental retardation or history of convulsive seizures, which is very rarely reported to the best of authors' knowledge.

Rapamycin therapy for neonatal tuberous sclerosis complex with cardiac rhabdomyomas: A case report and review.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease that varies greatly in its expression. The current study reports a novel case of TSC caused by a TSC2 mutation (TSC2c.1642_1643insA or TSC2p.K549fsX589), in which multiple cardiac rhabdomyomas were detected by fetal echocardiography in week 31 of pregnancy. The infant was delivered successfully; however, seizures began 16 days following birth. Subsequent genetic tests confirmed a diagnosis of TSC. Rapamycin treatment resulted in regression of cardiac rhabdomyomas and controlled seizures. The current study demonstrates the value of fetal echocardiography in the diagnosis of TSC and suggests that inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway may be considered as a potential antiepileptogenic therapy for neonatal TSC. In addition, it was demonstrated that rapamycin treatment was therapeutically beneficial for preventing disorders caused by abnormal mTOR signaling, such as cancer. According to the literature, cardiac rhabdomyomas, seizures and skin lesions are well established markers for TSC in neonates. MRI scans of the brain and genetic screening of TSC1 and TSC2 genes may facilitate an early diagnosis of TSC.

A case of tuberous sclerosis complex associated with non-functioning pituitary incidentaloma and moderate hyperprolactinaemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Tuberous sclerosis with cardiac rhabdomyoma: a case report

Tuberous sclerosis or tuberous sclerosis complex (TSC) is a genetic disorder, caused by mutations on either of two genes TSC1 and TSC2. Clinical manifestations are caused by growth of benign tumours in different parts of the body. Ten months old female child with four major criteria of tuberous sclerosis complex and asymptomatic cardiac rhabdomyoma is presented. A case of TSC warrants cardiac evaluation for the presence of cardiac rhabdomyoma and if a cardiac rhabdomyoma is detected on antenatal ultrasound or postnatal echocardiography, one should have high index of suspicion for the diagnosis of TSC. Continued research on this disease has unfolded many realities regarding its etiology as well as treatment.

A case of tuberous sclerosis complex revealed by epilepsy.

Tuberous sclerosis complex (TSC) is a multisystem genetic disease. Its incidence is estimated from 1/5800 to 1/1000 births. It results from the mutation of the TSC1 gene on chromosome 9 which codes for hamartin or the mutation of the TSC2 gene on chromosome 16 which codes for tuberin. In 80% of cases, it is linked to a neo-mutation and in 20% of cases it is autosomal dominant inherited from one of the parents. It is a multisystemic disease characterized by the presence of dysplasias, hamartomas and neoplasias in various organs: skin, kidneys, eyes, heart, lungs and mainly the brain. Clinically, epilepsy is the major complication of TSC and approximately 80-90% of patients will develop epilepsy in their lifetime. These epilepsies aren't specific but are generally characterized during evolution by their phamaco-resistance or by the complexity of the seizures. We report the case of a 12-year-old woman with partial epilepsy secondarily generalized, mental retardation and progressive facial angiofibromas (A) for 7 years. The electroencephalogram (EEG) performed 1 year ago showed bihemispheric irritant signs predominant at the frontotemporal right. The brain CT Scan with (B) and without injection of iodinated contrast agent (C) shows calcified subependymal nodules with supratentorial seat with bilateral asymmetric involvement and uncalcified cortical tubercles. The addition of the characteristic triad (convulsion, mental retardation and sebaceous adenoma) to the CT data enabled us to conclude a TSC. The evolution of convulsive seizures was significantly favorable under antiepileptic monotherapy (phenobarbital). On the other hand, mental retardation persists and angiofibromas continue to multiply at the facial level.

Gingival Overgrowth Leading to the Diagnosis of Familial Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC), a neurocutaneous syndrome, is characterized by the development of benign tumours affecting different body systems. We herein present a report of a 40-year-old female patient presenting with dental enamel pits and localized gingival overgrowth that eventually lead to the diagnosis of a case of familial TSC. Diagnosis of familial TSC by comprehensive oral examination and detection of oral manifestations proved to be inevitable as it resulted in institution of appropriate treatment strategies and genetic counselling of the affected family.

Tuberous sclerosis complex: Angiofibroma vipula/proliferanza?

Tuberous sclerosis complex (TSC) represents a genetic disorder of hamartoma formation in many organs; particularly the skin, brain, eye, kidney, and heart. We are reporting a case of TSC in a patient and his daughter. The interesting feature is the appearance of the facial angiofibromas in this patient. In this patient, there was a sudden spurt in growth of these lesions in the last 7 months at the age of 50 years giving an appearance of nodular growth, misleading the diagnosis. The lesion was biopsied to know any secondary changes had occurred. There is no mention in the literature regarding such a rapid growth or any secondary changes occurring in angiofibromas. Neither the biopsy revealed any secondary changes. Hence, this interesting phenomenon has been reported. Is it apt to call it as “ANGIOFIBROMA PROLIFERANZA” or “ANGIOFIBROMA VIPULA”? (The word VIPULA in local South Indian Kannada language is prolific growth).

Novel TSC1 Gene Mutation in a Familial Case of Tuberous Sclerosis Complex: A Case Report

Introduction: Tuberous sclerosis complex (TSC) is a genetic disorder that can arise from sporadic or inherited mutations in TSC1 or TSC2 genes. It is characterized by tumors in multiple organs that result in broad clinical manifestations, usually affecting the central nervous system. Diagnosis is based upon clinical criteria that require careful clinical examination along with imaging and the availability of genetic testing to assess gene mutations linked to this disorder. We present a familial case of tuberous sclerosis complex with multiple subtle clinical manifestations and novel TSC1 mutation that were diagnosed in adulthood. This report adds to the growing literature on TSC1 gene by correlating specific nucleotide substitutions with possible secondary clinical manifestations. Case presentation: A 21 year-old Hispanic female presented with history of epilepsy onset in early childhood. Upon clinical examination and imaging testing, she was found to have lesions on her scalp, eyes and brain. Her mother is 51 years old with long-standing history of epilepsy with multiple lesions on skin, eyes, and similar findings in brain imaging to daughter. No additional family history was obtained suggestive of tuberous sclerosis complex. Conclusion: Milder forms of tuberous sclerosis complex can remain undiagnosed until adolescence and adulthood, which may lead to treatment delay and complications due to the lack of regular follow-up care. In this case report, both individuals’ presenting symptom was epilepsy and later other clinical findings were linked to the disorder. Additionally, a novel DNA sequence variant was detected, which expands our knowledge of known TSC1 gene mutations. Although these genetic test results cannot be used alone to make a definite diagnosis, they suggest an association to TSC given the clinical manifestations and family history.

A subtle case of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is known to cause severe intractable epilepsy and mental retardation; however, diagnosis can be delayed in milder cases. We report a 26-year-old right-handed female patient who started having convulsions at age 7 days. She had several focal seizures per year that were intractable to treatment with carbamazepine or phenytoin. Her two sisters had several episodes of suspected epileptic seizures but had no symptoms related to TSC. Seizure semiology of the patient comprised of visual hallucination, loss of consciousness, and convulsive movements predominantly on the right. Physical examination revealed several small scattered angiofibromas over the nose that were histologically determined by skin biopsy. Hypomelanotic macules, shagreen patches, or periungual fibromas were not seen. Neurological examination showed mental retardation (MMSE: 23/30, WAIS-III: VIQ63, PIQ59, FIQ58) and decreased vibration sensation in both legs. Interictal EEG showed slow waves and epileptiform discharges broadly over the anterior quadrants bilaterally. Brain imaging showed multiple cortical tubers and malformation of cortical development but no subependymal nodules. Interictal IMP-SPECT showed hypoperfusion in the left frontal lobe. Cardiac rhabdomyoma was not noticed by cardiac echography. Truncal CT showed sclerosis of the bilateral lumbosacral joints. There was no abnormality in the lung, major arteries, liver, or kidneys. No hamartomas or retinal achromic patches were noticed by ophthalmologic evaluation. Administration of lamotrigine was effective for her seizures. This patient fulfilled two major features of diagnostic criteria for TSC and was diagnosed as definite TSC. Patients with mental retardation and epilepsy should be carefully evaluated for the possible diagnosis of TSC.

A Neonatal Case of Tuberous Sclerosis Complex (TSC) Associated with Sacrococcygeal Chordoma

A Neonatal Case of Tuberous Sclerosis Complex (TSC) Associated with Sacrococcygeal Chordoma

A case of tuberous sclerosis complex with bilateral advanced renal cell carcinoma

A case of tuberous sclerosis complex with bilateral advanced renal cell carcinoma