Lipomatosis

Lipomatosis is a hereditary condition where a person develops benign tumors ranging from a few millimeters in size to a few centimeters. Lipomas or benign tumors composed of fatty tissue are soft to the touch and usually painless. This rare condition usually does not usually necessitate any treatment unless the lipomas restrict movement. Ultrasound is now used to destroy the lipomas unlike the traditional method of surgical removal involving scarring. Lipomatosis is not life-threatening. But if the lipomas grow within the internal organs, it can lead to internal bleeding and ulceration.

Tuberous Sclerosis

This is a rare multi system genetic disease where benign tumors grow in the brain and other vital organs of the body such as kidneys, heart, eyes, lungs and skin. Tuberous Sclerosis is derived from the Latin word, tuber means swelling and the Greek Skleros means hard - a pathological finding of thick, firm and pale tubers in the patients. As these tubers were first described by Bourneville in 1880, it is sometimes known by the name Bourneville's disease.

Symptoms

A combination of symptoms including non-cancerous tumors or lesions in many parts of the body; in the brain, kidneys, heart, lungs and skin and also seizures, intellectual disability, developmental delay, skin abnormalities, lung and kidney disease.

Symptoms include

Skin abnormalities: Patches of light colored skin or small harmless areas of thickened skin or growth under or around the nails. Facial lesions resembling acne are common.

Seizures: due to lesions in the brain which can be the first symptoms of tuberous sclerosis. Infantile spasms in small children may occur.

Developmental delays: Intellectual disability and learning and developmental delays.

Behavior problems: Hyperactivity, raging outbursts, aggression, repetitive behaviors, social and emotional withdrawal.

Communication and social interaction problems: Children especially exhibit trouble with communication and social interaction and some may have autism spectrum disorder.

Kidney problems: develop lesions in kidneys which may damage kidney function.

Heart problems: Lesions may develop in the lungs and may cause coughing or shortness of breath, especially with physical activity or exercise.

Eye abnormalities: White patches develop on the light sensitive tissue at the back of the eye (retina). But these do not interfere with vision most of the times.

Causes

Tuberous sclerosis is caused by a mutation of either of two genes - TSC1 and TSC2 which code for proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation. The effect of these on the brain leads to neurological symptoms.

It is a rare genetic disease and is often detected during infancy or childhood. About one-third of the people with tuberous sclerosis inherit an altered TSC1 and TSC2 gene from a parent who has the disease. There is a 50% chance of passing the condition to the biological children although severity of the condition may vary. A parent with tuberous sclerosis may have a child with milder or severe form of the disorder.

Complications

Severe life-threatening complications can be caused depending upon where the tumors are developed and their size. Some complications that could develop are:

Lesions in the brain can block the flow of cerebral spinal fluid within the brain. This blockage can cause the buildup of fluid in the cavities, ventricles and within the brain leading to symptoms such as nausea, headaches and behavioral changes.

Lesions in the heart, especially in infants can block blood flow and cause problems in heart rhythm.

Lesions in the kidney can be large and life threatening - can cause bleeding or lead to kidney failure and sometimes become cancerous too.

Lesions in the lung can lead to lung failure. Lesions in the eye can interfere with vision.

Diagnosis

Patients are evaluated by different specialists including a geneticist, and those trained to treat problems of brain, heart, eyes, skin and kidneys. The doctors typically look for tumors who conduct tests to diagnose tuberous sclerosis. A child with seizures will undergo EEG as this can test the brain activity and help pinpoint what causes the child's seizures. Diagnostic testing to detect abnormal growths in kidneys and brain include MRI and CT and ECG to test electrical activity of the heart. In tuberous sclerosis, follow up monitoring is important and essential.

Treatment

Although there is no cure for tuberous sclerosis, treatment can help manage specific signs and symptoms. Education therapy can help children adapt to developmental delays and meet the classroom requirements. Medication may help manage behavioral problems. Everolimus is used to treat certain types of brain growths and kidney tumors that cannot be surgically removed. The topical ointment form of the drug called sirolimus can help treat acne-like skin lesions that can occur with tuberous sclerosis. Psychological therapy can help the child accept and adjust to living with this disorder. Physical therapy can improve his/her ability to handle daily tasks.

If the lesion affects the ability of a specific organ function, then surgery may be resorted to. Sometimes, surgery can control seizures caused by brain lesion in case medication fails. Dermabrasion or laser treatment may improve the appearance of skin lesions.

Family and support

Parents may consider genetic testing to confirm the diagnosis of tuberous sclerosis in their child, if the family history is not known. In case of a child diagnosed with tuberous sclerosis, there will be a number of challenges. It is essential to track the child closely with his/her peers in terms of academic, social and physical abilities. It is important to work closely with the child's doctor to establish an ongoing screening and monitoring schedule for health and developmental problems. Discovering and treating problems early will maximize the child's chances of a good outcome.

In case of early behavioral problems, it is essential to talk to the child's doctor and work with the child's school. Providing love and support is vital to help the child reach his/her full potential. It would also be helpful to connect with other families who are coping with tuberous sclerosis.

Neurofibromatosis

Neurofibromatosis (NF) also known as Von Recklinghausen disease is a relatively rare genetic disorder where the patients develop multiple benign tumors (neurofibromas). These tumors occur under the skin and throughout the nervous system. Neurofibromatosis occurs in about one in 4000 births. There are 2 types of Neurofibromatosis: Neurofibromatosis Type I (NF-1) is the most common - 90% of all cases and Neurofibromatosis Type II (NF-2) takes the remaining 10% of cases.

Causes of Neurofibromatosis :
Neurofibromatosis is caused by a defective gene - in the case of NF1, the defective gene responsible is chromosome 17 and in the case of NF2 , it is the chromosome 22. The defective gene manifestation is for half the cases. The other half is because of spontaneous mutation.

Symptoms:

• Presence of cafe-au-lait (brown/white) spots, patches of tan or light brown skin, usually about 5-15 mm in diameter.
  
• Multiple freckles in the armpit or groin area
  
• 90 % of cases of NF1 have tiny tumors called Lisch nodules in the iris (colored area) of the eye
  
• soft tumors are the hallmark of NF-1. They occur under the skin (plexiform neurofibromas) located along nerves or within the gastrointestinal tract
  
• Neurofibromas are small and rubbery and the skin overlying them may be somewhat purple in color
  
• Skeletal deformities - twisted spine (scoliosis), curved spine (humpback) or bowed legs
  
• Tumors along the optic nerve, which result in vision disturbance in about 20% of patients
  
• The presence of NF-1 in a patient’s parent, child or sibling
  
• speech impairment, learning disabilities and attention deficit disorder
  
• seizure disorder
  
• abnormal accumulation of fluid within the brain (hydrocephalus)
  

Apart from the above mentioned symptoms, the NF1 patients are susceptible to malignant brain tumors, as well as leukemia and cancerous tumors of certain muscles (rhabdomyosarcoma), the adrenal glands (pheochromocytoma) or the kidneys (Wilms’ tumor).

NF-2 symptoms: Tumors along the acoustic nerve resulting in the loss of hearing. If the tumor spreads to the neighboring nervous system it will cause weakness of the muscles of the face, headache, dizziness, poor balance and uncoordinated walking. Cataracts may form at an early age. Chances of developing brain tumors are high.

Diagnosis: If the presence of 2 or more symptoms mentioned above is there, it calls for additional steps in diagnosis. Diagnosis of NF-2 requires the presence of either a mass on the acoustic nerve or another distinctive nervous system tumor. The most diagnostic factor is the presence of the disorder in a patient’s parent, child or sibling. Careful testing of vision and hearing is mandatory to know about the progression of Neurofibromatosis. In addition X-rays of the bones will help to track the development of deformities. CT/MRI scans also help to check for the progression of tumors.
The electric response evoked in the cerebral cortex by stimulation of the acoustic nerve will be quite useful to determine the involvement of the acoustic nerve, while EEG (electroencephalogram) may be useful for suspected seizures.

Treatment: As of now, there are no treatment options available. The symptoms of NF1 /NF2 are treated individually. Tumors are removed surgically wherever possible. Some cases may require Chemotherapy or radiation therapy. Curving of spine or bowed legs (tibial dysplasia) may be corrected by special braces.

Prognosis varies depending upon the individual cases. If the tumors continue to grow, they may destroy the surrounding nerves. Blindness, loss of hearing and poor balance may be the outcome.