TUBEROUS SCLEROSIS (TS)

 

 

  • TS is an autosomal dominant disease characterized by benign harmatomas in multiple organs including brain heart, skin and kidneys.
  • 50-70% of cases of TS result as a new spontaneous gene mutation (1).
  • TS is genetically heterogeneous, but most families show linkage to one of  two genes that have tumor suppression function: TSC1 located at 9q34 and TSC2 located at 16p13 (2).

 

Prevalence at birth = 1:5800-10000 (3-5).

 

Triad of clinical features - Seizures

                                          - Mental deficiency.

                                          - Adenoma sebaceum.

The clinical picture is, however, variable both within and amongst families. Persons with milder form may be completely unaware of the disease.

 

 

ULTRASOUND

 

1. Cardiac rhabdomyomas - this is the most common manifestation in the antenatal period (6).

-          may be detected as early as 20 of gestation (7).

-          50-80% of antenatally diagnosed rhabdomyomas are liked to TS.

-          When rhabdomyomas are isolated, the functional and general progosis is good as they tend to regress spontaneously.

-          Cardiac failure may occur prior to complete regression (12).

 

 

 

 

Video clip of a Rhabdomyoma of the right ventricle

 

 

 

 

 

2. Central nervous system tumors detected at antenatal ultrasound is rare.

             - large and hyperechogenic in frontal, parietal and temporal regions causing mass effect and midline shift (8).

             - ventriculomegaly may be present due to subependymal nodules and cortical tubers with are usually undetectable on antenatal scanning (6,9).

3. Facial angiomas, ungal angiomas and renal angiomyolipomas are not detectable antenatally as they are not present at birth developing only after the first year of life (1).

 

CT scan and MR images have been used antenatally to detect subtle CNS findings in a fetus at risk (family history or the presence of cardiac rhabdomyomas).

MR imaging is more sensitive than CT in the early detection of CNS tumors, as subcortical tumors may be isodense with normal cortex (10,11).

A normal prenatal MR scan does not, however, exclude the diagnosis of TS.

 

 

REFERENCES

 

1. Kwiatowski DJ, Short MP. Tuberous sclerosis. Arch Dermatol 1994;130:348.

2. Elcioglu N, Karatekin G, Elcioglu M et.al. Tuberous sclerosis: Clinical evaluation in a family and implications for genetic counseling. Genet Couns 1998;9:131.

3. Sampson JR, Scahill SJ, Stephenson JB et.al. Genetic aspects of tuberous sclerosis in the west of Scotland. J Med Genet 1989;26:28.

4. Shepherd CW, Beard CM, Gomez MR et.al. Tuberous sclerosis complex in Olmstead County, Minnesota, 1950-1989. Arch Neurol 1991;48:400.

5. Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann NY Acad Sci 1991;615:125.

6. Gava G, Buoso G, Beltrame GL et.al.  Cardiac rhabdomyoma as a marker for prenatal detection of tuberous sclerosis. Case report. Br J Obstet Gynecol 

    1990;97:1154.

7. Wallace G, Smith HC, Watson GH et.al. Tuberous sclerosis presenting with fetal neonatal cardiac tumors. Arch Dis Child 1990;65:377.

8. Muller L, deJong G, Falck V et.al. Antenatal sonographic findings in tuberous sclerosis. S Afr Med J 1986;69:633.

9. Mitra AG, Dickerson C. Central nervous system tumor with associated unilateral ventriculomegaly: Unusual prenatal presentation of subsequently diagnosed tuberous 

    sclerosis. J Ultrasound Med 2000;19:651-654.

10.Revel MP, Pons JC, Lelaider C et.al. Magnetic resonance imaging of the fetus: a study of 20 cases performed without curarization. Prenat Diagn 1993;13:775.

11.Sonigo P, Elmaleh A, Fermont L et.al. Prenatal MRI diagnosis of fetal tuberous sclerosis. Pediatr radiol 1996;26:1.

12.Axt-Fliedner R, Qush H, Hendrick HJ et.al. Prenatal diagnosis of cerebral lesions and multiple intracardiac rhabdomyomas in a fetus with tuberus sclerosis. J Ultrasound 2001;20:63-67.