|Year : 2021 | Volume
| Issue : 3 | Page : 208-211
Tuberous sclerosis complex patient fulfilling the criteria set by the 2012 international tuberous sclerosis complex consensus conference
Aimen Malik1, Arshia Akbar1, Gohar Ashraf2, Hammad Akram3
1 Medicine, Holy Family Hospital, Rawalpindi, Pakistan
2 Pediatrics, Lehigh Valley Hospital, Allen Town, PA, USA
3 Epidemiology, Independent Collaboration, Texas, USA
|Date of Submission||23-Jun-2021|
|Date of Decision||16-Jul-2021|
|Date of Acceptance||19-Jul-2021|
|Date of Web Publication||07-Sep-2021|
2704 OZ. Cv. DFW, Texas
Source of Support: None, Conflict of Interest: None
Tuberous sclerosis complex (TSC) is a rare multisystem neurocutaneous disorder associated with the growth of benign tumors in different organs such as the brain, lungs, kidneys, heart, and eyes. The dermatological findings of this disorder are very common, present at early age and not easy to miss. The neurological manifestations of TSC include seizures, autism, and intellectual disabilities. Furthermore, intracranial abnormalities and hamartoma formation in the heart and other organs are found among sufferers. The clinical diagnostic criteria have been critically evaluated and updated in the 2012 International Tuberous Sclerosis Conference. The diagnosis is based on genetic criteria, clinical criteria, and various manifestations of skin, kidneys, lungs, and brain. The management involves multispecialty and multidisciplinary approaches. Here, we present a case of a 13-year-old female with characteristic clinical, radiological, and pathological features of TSC.
Keywords: Adolescents, angiofibroma, angiomyolipoma, autosomal dominant disorder, dermatology, genetic disorders, hamartomas, multisystem disorder, neurocutaneous disorder, rare diseases, skin patches, tuberous sclerosis complex, tuberous sclerosis complex criteria
|How to cite this article:|
Malik A, Akbar A, Ashraf G, Akram H. Tuberous sclerosis complex patient fulfilling the criteria set by the 2012 international tuberous sclerosis complex consensus conference. Apollo Med 2021;18:208-11
|How to cite this URL:|
Malik A, Akbar A, Ashraf G, Akram H. Tuberous sclerosis complex patient fulfilling the criteria set by the 2012 international tuberous sclerosis complex consensus conference. Apollo Med [serial online] 2021 [cited 2021 Dec 6];18:208-11. Available from: https://www.apollomedicine.org/text.asp?2021/18/3/208/325678
| Introduction|| |
Tuberous sclerosis complex (TSC) is a rare multisystem autosomal-dominant neurocutaneous disorder characterized by hamartomas in different organ systems., The hamartomatous lesions can be found anywhere; however, common locations are the brain, lungs, kidneys, heart, and eyes., The prevalence of TSC is not clear, however, ranges anywhere from 1 in 6000 to 1 in 10,000 among newborns and overall, 1 in 10,000–30,000 individuals, respectively, and around 2 million suffering from it globally. The predisposition based on race, ethnicity, and gender has not been found; however, due to a shorter life expectancy, the prevalence seems to be lower among older persons and confounded by age.
There are more than 1500 known pathogenic variants for TSC1 and TSC2, including deletion, nonsense, and missense mutations, and all pathogenic mutations are inactivating, leading to loss of function effects on the encoded proteins TSC1 and TSC2. According to the International TSC Consensus (2012), the disorder is diagnosed through clinical manifestations and/or genetic basis. The identification of the mutation in TSC 1 or TSC 2 genes which encode hamartin and tuberin, respectively, is sufficient for definitive diagnosis.
Here, we are present a case report of a young female with a history of childhood epilepsy and mental retardation who was admitted to us with fever, increased frequency of convulsions, hematuria, and abdominal pain.
| Case Report|| |
A 13-year-old Asian female presented in the Emergency Department of Holy Family Hospital in Rawalpindi, Pakistan. The patient had a 10-day history of fever, lower abdominal pain, and hematuria (painful) along with increased frequency in convulsions for the past 4 days. She had a known history of generalized tonic-clonic seizures since the age of 8 months and was on antiepileptic drugs including valproic acid and carbamazepine with good compliance to the treatment, however, with poor control of seizures. The patient had delayed achievement of physical and mental milestones.
Clinical examination revealed an irritable teenage girl with a lean built. She was febrile, had tachycardia (pulse rate 120 bpm), and reddish urine in the drain. Examination showed multiple facial angiofibroma appearing as multiple brownish lesions in a butterfly pattern with sparing of the forehead and shagreen patch on the cheek [Figure 1].
|Figure 1: Skin manifestations of tuberous sclerosis complex: Multiple angiofibroma lesions on the face, nasal polyp in the right nostril and shagreen patch visible on the left cheek, ash-leaf spot visible on the limb, and confetti lesion on thigh|
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Oral examination revealed dental enamel pits. Four ash-leaf spots were noted on the right lower limb, confetti lesions were found on the thighs, abdomen, and both breasts [Figure 1]. A nasal polyp was also seen [Figure 1]. Retinal examination revealed bilateral astrocytic hamartomas.
Laboratory showed low hemoglobulin level (4.0 g/dL), high total leukocytes (21 × 109/L) and platelets counts (521 × 109/L), and normal hepatorenal function tests. Urine examination revealed numerous pus and red blood cells. Abdominal ultrasonography showed a large heterogeneous lesion (9.4 × 7.4 cm) with internal cystic and necrotic components in the right lumbar region which could be of hepatic or renal origin. Computed tomography (CT) of the abdomen revealed bilateral angiomyolipoma (AML), right kidney with intralesional and subcapsular hemorrhage, multiple renal cysts, hepatosplenomegaly, mild abdominopelvic ascites, and mild cystitis [Figure 2]. CT of the brain showed multiple calcified and noncalcified cortical and subcortical tubers, subependymal nodules along bilateral lateral ventricle walls, and right cerebellar-folial calcifications [Figure 3]. An electrocardiogram showed sinus tachycardia (also evident during examination i.e. pulse was ~120 beats/min) without any other abnormality in the rhythm and/or electrical activity. Echocardiography detected multiple nodular structures in the myocardium likely to be rhabdomyomas. Colonoscopy studies were normal.
|Figure 2: Computed tomography of the abdomen showing bilateral renal angiomyolipoma with intralesional and subcapsular hemorrhage, multiple renal cysts, hepatosplenomegaly, and mild abdominopelvic ascites|
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|Figure 3: Computed tomography of the brain showing cortical and subcortical lesions and calcifications (left) and cerebellar-folial calcification (right)|
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| Discussion|| |
Manifestations of TSC can appear at any age, but most of the patients become symptomatic before 10 years of age. The new criteria, i.e., International TSC Consensus-2012, are shown in [Table 1].
|Table 1: Major and minor tuberous sclerosis complex criteria as per the International Tuberous Sclerosis Complex Consensus 2012|
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A definite diagnosis is made when a patient meets two major or one major plus three minor criteria. The possible diagnosis is established when one major (without any minor) or two or more minor criteria (without any major) are present among patients. Exception to this rule is lymphangioleiomyomatosis (LAM) and AMLs (both major criteria features): if these two are present in absence of any other feature(s), the diagnostic criteria are not fulfilled. According to this new diagnostic tool, our patient followed 8 major and 4 minor criteria, as shown in [Table 1] in bold fonts.
Among cutaneous lesions, the ash-leaf spots are the most common and earliest presenting features among patients. Another common skin lesion is adenoma sebaceum which is a connective tissue hamartoma with vascular element also termed as angiofibroma and pathognomonic of tuberous sclerosis as it is present among over 70% of cases., Intracranial lesions include cortical or subcortical tubers, subependymal nodules, giant cell astrocytoma, and white matter radial migration lines. Initially, tubers appear as hypodense subcortical lesions and later on isodense on a nonenhanced CT scan. Half of these lesions calcify by 10 years of age which appear as hyperdense nodules that get enhanced after contrast and rarely can be seen in the cerebellum. Since radial migration lines and cortical tubers are usually present together and have similar pathogenesis, these together are now labeled as “cortical dysplasia.” Renal AML is associated with 20% of TSC patients. Our patient had bilateral renal AML along with cystic changes. Renal AMLs are benign usually asymptomatic tumors and can be managed conservatively; however, if the tumor size is >4 cm, surgical approaches such as renal artery embolization and partial nephrectomy can be carried out to prevent any bleeding and impairment of renal functions. Furthermore, everolimus (mTOR C1 inhibitor), an antineoplastic, is found to be beneficial in AML associated with TSC, especially if there are multiple lesions., Cardiac rhabdomyoma is also a benign tumor identified usually during echocardiography among 50% of TSC cases and is usually present with no symptoms; however, can be associated with rhythm abnormalities and/or blood flow interference due to the mass effect of the lesions., Ophthalmic features can be divided into retinal, for example, astrocytic hamartomas and nonretinal lesions such as papilledema, angiofibroma, and coloboma., Pulmonary LAM is present in 1%–3% of cases. Gastrointestinal manifestations include fibromas in the nasopharynx and esophagus, hamartomatous polyps in the stomach, or rectum. Hepatobiliary lesions include hepatomegaly, AML, lipomas, and hamartomas. The multifaceted conditions such as TSC can lead to multimorbidity, the management of which can be challenging and requires multidisciplinary interventions.
| Conclusion|| |
To our knowledge, this is the first report on a patient with TSC who fulfills 8 major and 4 minor criteria.
The authors thank the patient's parents for allowing us to publish this case report.
Written consent was obtained from the patient's parents for this case report.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents has given their consent for her images and other clinical information to be reported in the journal. The patient's parents understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]