Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 8  |  Issue : 3  |  Page : 401-403  

Varied manifestations of tuberous sclerosis


1 Department of Medicine, University College of Medical Sciences, New Delhi, India
2 Department of Radio-Diagnosis, University College of Medical Sciences, New Delhi, India

Date of Web Publication15-May-2015

Correspondence Address:
Nikhil Gupta
C-158 Pushpanjali Enclave, Pitampura, New Delhi - 110 034
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.150504

Rights and Permissions
  Abstract 

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease. The prevalence of TSC is estimated to be 1 in 95,136 in general population and in those <6 years of age, it is 1 in 14,608. It is an autosomal dominant neurocutaenous disease and in about 80% of cases it is caused by a de novo mutation. The relationship between cardiac rhabdomyomas and TSC is well established. The cardiac rhabdomyomas may arise anywhere in the myocardium but are more commonly seen in the left ventricle. However, in our case an interventricular septal rhabdomyoma was seen. Angiomyolipomas (AMLs) occur in up to 80% of patients with TSC. Bilateral renal AMLs were seen in our case. There was evidence of systemic involvement in form of lymphangiomyomatosis and subependymal hamartomas.

Keywords: Angiomyolipoma, cardiac intra ventricular septal rhabdomyoma, tuberous sclerosis


How to cite this article:
Gupta N, Khurana S, Malik S, Agarwal S. Varied manifestations of tuberous sclerosis. Med J DY Patil Univ 2015;8:401-3

How to cite this URL:
Gupta N, Khurana S, Malik S, Agarwal S. Varied manifestations of tuberous sclerosis. Med J DY Patil Univ [serial online] 2015 [cited 2020 Sep 18];8:401-3. Available from: http://www.mjdrdypu.org/text.asp?2015/8/3/401/150504


  Introduction Top


Tuberous sclerosis complex (TSC) also called Bourneville's disease. The prevalence of TSC is estimated to be 1:95,136 and those <6 years of age is 1:14,608. [1] It is an autosomal dominant neurocutaenous disease and about 80% is caused by de novo mutation. [2] Cardiac involvement in TSC is characterised by presence of rhabdomyomas. They may present as arrythmias, heart failure or ventricular inflow or outflow tract obstruction. The cardiac rhabdomyomas may arise anywhere in the myocardium but are more commonly seen in the left ventricle. However, in our case an interventricular septal rhabdomyoma was seen. Angiomyolipomas (AMLs) occur in up to 80% of patients with TSC. [3] Thus, this case reveals an important but rare site for cardiac rhabdomyoma.


  Case Report Top


A 35-year-old female, presented to us with the complaint of 1 episode of seizure which were generalized tonic clonic in semiology. She was a diagnosed case of epilepsy since the age of 1½ months and had been on anti-epileptic medication (valproate) in past and it was self-discontinued around 10 years ago. The fits were associated with urinary incontinence, frothing, and up rolling of eyeballs. There was no history of tongue bite. There was history of mental retardation. Although her milestones were not delayed, she was able to speak only in small sentences. She had acute visual loss at the age of 10 years.

On physical examination, she was restless, with a Glasgow coma scale of 7/15. Her vitals were stable. Physical signs revealed facial angiofibromas, hypomelanotic macules in lower abdomen and periungal fibromas in the left thumb.

A shagreen patch was present in the right lower lumbar region. Patient was put on valproate. Patient became conscious and oriented over a span of 1 h. Investigations showed a normal complete blood count. Besides routine tests, her serum levels of calcium, sodium, potassium phosphorus, and magnesium were within normal limits. Fundus examination was normal. Electrocardiographic and pulmonary function test were normal. Patient underwent contrast enhanced computed tomography (CT) of abdomen which showed presence of well-marginated, cortical-based, heterogeneously enhancing tumor, predominantly of fat density (<−20 HU) in bilateral kidneys s/o renal AMLs [Figure 1]. Patient was further subjected to contrast enhanced CT thorax that revealed multiple variable sized cysts distributed randomly in bilateral lung fields with intervening normal lung parenchyma in between the cysts suggestive of lymphangiomyomatosis (LAM) like changes in bilateral lung fields [Figure 2]. A hypodense non enhancing lesion was noted in the interventricular septum, likely a septal rhabdomyoma [Figure 2] and rest of the cardiac chambers were normal. To further evaluate, noncontrast CT cranium was also done that showed the presence of multiple calcified periventricular subependymal nodules with basal ganglia calcification [Figure 1]. A gene analysis was done and patient was found to have a mutation in gene TSC 2. Patient refused treatment with Rapamycin. Laser therapy reduced the size of facial angiomas. Patient is under a regular follow up from psychiatric clinic. Her brother was screened for mutation of TSC gene and was found to have a TSC 2 gene mutation as well. He had various clinical manifestations of TSC including left ventricle cardiac rhabdomyoma. Rest of the relatives of the patient had died in an accident 8 years ago.
Figure 1: Contrast enhanced computed tomography (CT) of abdomen showing presence of well-marginated, cortical-based, heterogeneously enhancing tumor, predominantly of fat density (<−20 HU) in bilateral kidneys s/o renal angiomyolipomas. This image also shows non contrast CT cranium revealing the presence of multiple calcified periventricular subependymal nodules with basal ganglia calcification

Click here to view
Figure 2: Contrast enhanced computed tomography thorax showing multiple variable sized cysts distributed randomly in bilateral lung fields with intervening normal lung parenchyma in between the cysts suggestive of lymphangiomyomatosis like changes in bilateral lung fields. A hypodense non enhancing lesion was noted in the interventricular septum, likely a septal rhabdomyoma

Click here to view


Summarizing her history, extensive physical signs and investigations, the final diagnosis of TSC was made.


  Discussion Top


Tuberous sclerosis is a autosominal dominant neurocutaneous syndrome with benign hamartomatous lesions involving multiple organ systems of the body. There appears to be a chronological pattern of organ involvement; cardiac rhabdomyomas occur in antenatal and neonatal period, renal AMLs become more frequent with increasing age. [4] Though, the gender predilection has not been reported, except LAM that affects only females.

Tuberous sclerosis is also characterized by angiofibromas formation on the face which leads to cosmetic issues to the patient. Diagnosis can be delayed due to late manifestations of some symptoms. Some patients may present with only renal and pulmonary manifestations while in some skin or neurological manifestations might be absent. However, in our case, the patient had skin and neurological features as the presenting complaints.

Cardiac rhabdomyomas mostly present in neonatal period. Often multiple lesions are seen in one or both ventricles (more commonly left ventricle), [5] rhabdomyomas have also been rarely reported in interventricular septum. Our patient had an incidentally discovered interventricular septum rhabdomyoma. These lesions are seen as smooth, round, intraventricular masses with characteristics similar to normal heart.

Intracranial involvement can be complex involving cortical, subcortical, subependymal and cerebellar tissue. Periventricular subependymal hamartomas are seen which may show calcification in 90% cases. [6] When at foramen of monro these hamartomas may rarely transform into giant cell astrocytoma. Cortical and subcortical tubers are seen as hypodense lesions on CT. Rarely, they may appear hyperdense. Magnetic resonance imaging (MRI) is superior in identifying cortical tubers. Our patient too was found to have subependymal hamartomas with calcification.

Renal involvement is seen in 60% of cases of TSC with AMLs being the most common lesion. [5] TSC accounts for 20% of all AMLs that tend to be multiple, large, bilateral. On ultrasonography, they are seen as heterogenous masses with predominantly hyperechoic fat content. [6] In few cases multiple simple cysts are also seen in combination with AML. On CT, they are seen as hypodense lesions due to fat content which makes them hyper intense on T1-weighted MRI with complete loss of signal on fat suppressed sequences. Intrarenal haemorrhage has been reported as a complication. [7] Our patient was found to have an asymptomatic bilateral AML on work up.

High resolution computed tomography thorax may show multiple, variable sized cysts distributed in bilateral lung fields with normal intervening lung parenchyma suggestive of LAM. Hamartomatous proliferation of pneumocytes may also be seen in addition to LAM. Renal AML may be observed in 50% of patients affected with TSC. [8] LAM co-exists with TSC and a possible relationship between LAM and TSC is under investigation. [8]

Webb, in his study, found skin signs to be present in 96% of patients with TSC. [9] However, in another study, dermatologic features were found to be presenting signs in only 6% of patients with TSC. [10]

In addition, hamartomatous polyps may occur anywhere from oesophagus to rectum, most commonly involving large bowel. Musculoskeletal involvement is seen as a patchy increase in bone density.

As has been reported in the literature, multisystem involvement is also noted in our case with an uncommon location of cardiac rhabdomyoma seen in the interventricular septum with bilateral large renal AMLs, with lung changes suggestive of LAM, along with skin manifestations and intracranial periventricular subependymal hamartomas with calcification.

Our case was diagnosed using criteria adopted from Roach and Sparagana. [11] Our patient fulfilled more than 2 major criteria which include cardiac rhabdomyoma, renal angiomyolioma, shagreen patch, facial angioma's, hypomelanotic macules and periungal fibromas.


  Conclusion Top


The cardiac rhabdomyomas may arise anywhere in the myocardium but are more commonly seen in the left ventricle. However, in our case an interventricular septal rhabdomyoma was seen. Thus, our case demonstrates a rare location of cardiac rhabdomyomas in TSC patients.

 
  References Top

1.
Hong CH, Darling TN, Lee CH. Prevalence of tuberous sclerosis complex in Taiwan: A national population-based study. Neuroepidemiology 2009;33:335-41.  Back to cited text no. 1
    
2.
Staley BA, Vail EA, Thiele EA. Tuberous sclerosis complex: Diagnostic challenges, presenting symptoms, and commonly missed signs. Pediatrics 2011;127:e117-25.  Back to cited text no. 2
    
3.
Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006;355:1345-56.  Back to cited text no. 3
    
4.
Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA. Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors. Kidney Int 2006;70:1777-82.  Back to cited text no. 4
    
5.
Casper KA1, Donnelly LF, Chen B, Bissler JJ. Tuberous sclerosis complex: Renal imaging findings. Radiology 2002;225:451-6.  Back to cited text no. 5
[PUBMED]    
6.
Adriaensen ME1, Schaefer-Prokop CM, Stijnen T, Duyndam DA, Zonnenberg BA, Prokop M. Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol 2009;16:691-6.  Back to cited text no. 6
[PUBMED]    
7.
Evans JC, Curtis J. The radiological appearances of tuberous sclerosis. Br J Radiol 2000;73:91-8.  Back to cited text no. 7
    
8.
Cohen MM, Pollock-BarZiv S, Johnson SR. Emerging clinical picture of lymphangioleiomyomatosis. Thorax 2005;60:875-9.  Back to cited text no. 8
    
9.
Webb DW, Clarke A, Fryer A, Osborne JP. The cutaneous features of tuberous sclerosis: A population study. Br J Dermatol 1996;135:1-5.  Back to cited text no. 9
    
10.
Yates JR, Maclean C, Higgins JN, Humphrey A, le Maréchal K, Clifford M, et al. The tuberous sclerosis 2000 study: Presentation, initial assessments and implications for diagnosis and management. Arch Dis Child 2011;96:1020-5.  Back to cited text no. 10
    
11.
Roach ES, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol 2004;19:643-9.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Case Report
Discussion
Conclusion
References
Article Figures

 Article Access Statistics
    Viewed2245    
    Printed23    
    Emailed0    
    PDF Downloaded121    
    Comments [Add]    

Recommend this journal