Tuberous Sclerosis

Description

Tuberous sclerosis is one of the phakomatoses (“birthmarks”), the congenital or heritable conditions characterized by hamartomas and neoplasms throughout the body. Other phakomatoses include Neurofibromatosis, von Hippel-Lindau disease (retinal capillary hemangioma), Sturge-Weber syndrome, ataxia-telangiectasia and Wyburn-Mason syndrome.

Tuberous sclerosis is a neurocutaneous syndrome affecting multiple organ systems. Structural lesions in tuberous sclerosis are usually hamartomas – i.e., benign, disorganized proliferations of mature cells native to the affected organ. Typical brain lesions are superficial cerebral cortical ‘tubers’ or periventricular nodules, causing possible seizures and cognitive impairment. Other clinical features include a variety of skin lesions, visceral (particularly renal) pathology, cardiac and lung lesions and astrocytic hamartomas of the retina or optic disc. Inheritance is autosomal dominant. However, since most patients do not reproduce, approximately 75 percent of cases represent spontaneous mutations in the tumor suppressor genes TSC1 or TSC2 (located on chromosomes 9 and 16, respectively).

Symptoms

Up to 98 percent of patients have seizures, 75 percent within the first year of life. Most patients have some degree of cognitive impairment. Renal lesions may present with flank pain, hematuria, an abdominal mass, hypertension or renal impairment. Symptoms of lung involvement may include cough, dyspnoea or hemoptysis. Retinal hamartomas are usually asymptomatic.

Signs

Astrocytic hamartomas of the retina or optic disc are the principal ocular manifestation of tuberous sclerosis. The appearance of retinal hamartomas ranges from flat, pale, semitransparent lesions to raised, calcified and nodular ‘mulberry-like’ tumors. Adjacent retinal vessels may be dilated, and arteriovenous malformations are occasionally observed. In rare cases, these retinal vascular abnormalities may rupture, resulting in vitreous hemorrhage.

Optic disc swelling has been reported in several cases. It is usually bilateral and may progress to optic atrophy. Ocular motility problems may include strabismus or nystagmus, and third or sixth nerve palsies.

The eyelids are rarely affected by angiofibromas, vitiligo, ptosis or epicanthic folds. Examination of the skin often reveals depigmented patches, which are often pointed at one end and round at the other, resembling the leaves of the mountain ash tree (‘ash leaf patches’). Angiofibromas typically proliferate over the nose and cheeks during puberty; their red, vesicular appearance may be mistaken for acne vulgaris. Shagreen patches are thickened patches of discolored skin, usually over the lumbar area. Other skin lesions include forehead fibrous plaques, subungual and periungual fibromas and skin tags.

Prevalence

Rare (approximately 1 in 10,000). Astrocytic hamartomas of the retina or optic disc occur in up to half of patients, and are bilateral in a third.

Significance

Systemic assessment and genetic counseling is indicated in all cases.

Differential Diagnosis

Retinoblastoma.

See Also

Neurofibromatosis Type 1, Neurofibromatosis Type 2.

Management

Additional investigations

Neurological management includes cerebral imaging and anticonvulsant medications. Renal and cardiac assessment includes blood & urine tests, abdominal imaging and electrocardiography (ECG).

Review

Although retinal astrocytomas generally cause no symptoms and require no specific treatment, yearly ocular review is recommended to enable detection and treatment of rare complications.

Genetics

A thorough family history is compiled, and other family members are examined. Genetic counseling is offered to affected patients and their families.