genetic diseases

Tuberous Sclerosis Symptoms

Related articles: Tuberous sclerosis

Definition

Tuberous sclerosis is a neurocutaneous syndrome that affects several organs and causes the development of numerous tumors.

The origin of this disorder is genetic and, mainly, depends on mutations occurring in two genes of tumor suppressors, TSC1 (chromosome 9) and TSC2 (chromosome 16). These genes codify respectively for the amartina and tuberina proteins, which modulate cell growth and multiplication and, as a rule, contribute to tumor suppression.

Tuberous sclerosis is transmitted in an autosomal dominant manner; therefore, within the same family, if one of the two parents is affected, the risk for the offspring to inherit the disease is 50%.

The syndrome can also occur sporadically (spontaneous mutations), without there being any previous cases in the family.

Most common symptoms and signs *

  • Arrhythmia
  • cataplexy
  • Convulsions
  • Learning difficulties
  • Skin discoloration
  • Dyspnoea
  • Abdominal pain
  • Temperature
  • Hydrocephalus
  • Hydrops Fetal
  • Insomnia
  • Hypertension
  • Intracranial hypertension
  • lipotimia
  • macules
  • Backache
  • myoclonus
  • Nodule
  • plaques
  • pneumothorax
  • Mental delay
  • Blood in the urine
  • Muscle spasms
  • Uremia
  • Pleural effusion

Further indications

Tuberous sclerosis is a multisystemic syndrome that mainly affects the skin, brain, heart and kidneys. Overall, the manifestations of the disease are extremely variable.

At cutaneous level, the disease involves clear congenital lesions of lanceolate (leafy) or round shape (hypomelanotic macules) and knurled plaques (detected lesions similar in consistency to an orange peel), generally at the level of the back.

Tuberous sclerosis causes facial angiofibromas and fibrotic plaques (ie, circumscribed thickening of the skin) on the forehead and scalp. Furthermore, during childhood or late adolescence, subcutaneous nodules, coffee-milk spots and subungual fibroids of the hands and feet may appear.

Depiction of a case of tuberous sclerosis showing facial angiofibromas with the characteristic butterfly distribution. See other Tuberous Sclerosis Photos

Many children present with renal cysts and angiomyolipomas (benign tumors of vascular, smooth muscle and fatty tissue), which can cause, in adulthood, hypertension, polycystic kidney disease, hematuria, uremia, fever and abdominal pain.

Some patients also present with fetal or neonatal onset heart injuries, such as rhabdomyomas (benign tumors of cardiac cells), usually asymptomatic. At the level of the nervous system, however, cortical tubers (roundish thickenings of the brain's convolutions), white matter dysplasias and brain tumors, generally astrocytomas, can be observed. Tuberous sclerosis can also determine the formation of cysts and nodules in the walls of the cerebral ventricles.

Children may experience seizures in the first months of life or during infancy (partial seizures, absences and myoclonic or atonic seizures). Epilepsy is, in fact, the most frequent neurological manifestation of tuberous sclerosis (and often difficult to control).

As the child grows, behavioral changes may occur with or without cognitive deficits, learning and sleep disorders and, in the most serious cases, autistic phenotype.

Other lesions that can be found in the context of the syndrome include retinal hamartomas and enamel anomalies of deciduous and permanent teeth.

In adulthood, tuberous sclerosis can be associated with lymphangioleiomyomatosis, a condition in which small diffuse angiolipomatous masses gradually replace the lung parenchyma, causing respiratory difficulties, pneumothorax and pleural effusion.

Tuberous sclerosis is diagnosed by imaging the affected organs (MRI or ultrasound) and specific genetic testing. Not all clinical signs of the disease are present in the same individual.

Prenatal diagnosis by villocentesis or amniocentesis can be performed if the mutation has already been identified in a parent or another child. The prognosis depends on the severity of the symptoms: infants with mild symptoms generally have a good prognosis, while those with severe manifestations may have an important disability.

The treatment of tuberous sclerosis is symptomatic and may include drugs (due to epileptic seizures and neurobehavioral problems), dermabrasion or laser techniques (for skin diseases), antihypertensives or surgical removal of growing tumors, behavioral management techniques and school support.