The correct answer is Tuberous Sclerosis.

Video 1 - Video of the patient suffering from Tuberous Sclerosis
Video 2 - Video of the patient's daughter who is also suffering from Tuberous Sclerosis

Image 1 - Adenoma Sebaceum

Image 2 - Facial Angiofibromas

Image 3 - Fibromas in the mouth

Image 4, 5, 6, 7 - Periungual Fibromas

Image 8 - Bone Cysts

Image 9 - Renal Angiomyolipoma

Image 10 - Subependymal nodules

Image 11 - Facial Angiofibromas

Image 12 - Shagreen Patch on Patient's Daughter's Back

Tuberous Sclerosis

DEFINITION

Tuberous sclerosis (TS) is an inherited neurocutaneous disorder that is characterized by pleomorphic features involving many organ systems, including multiple benign neoplasms (hamartomas) of the brain, kidney, and skin.

GENETICS:

• TS is an autosomal dominant disorder with almost complete penetrance but a wide range of clinical severity. However, only one third of cases are familial. The apparently nonfamilial cases can represent either spontaneous mutations or mosaicism.
• Genetic research has identified two TS genes. One is located on chromosome 9 (TSC1 gene) and the other on chromosome 16 (TSC2 gene). About 68% of cases occur as a result of new gene mutations. Because of the genetic transmission and new mutations, antenatal diagnosis is difficult.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

• Dermatologic manifestations may be the only clues the family physician has to the diagnosis of the disorder, which is also marked by childhood seizures and mental retardation.
• The diagnostic criteria for TS were recently revised at a consensus conference. .
• The classic diagnostic triad of seizures, mental retardation, and facial angiofibromas (Vogt’s triad) occurs in fewer than 50% of patients with TS.
• All of the clinical features of TS may not be apparent in the first yr of life. Thus, a child is often initially diagnosed with possible or probable TS and the diagnosis of definite TS is made after additional features are identified.
• Dermatologic manifestations: A careful skin examination of patients at risk for TS continues to be the easiest and most accessible method of establishing the diagnosis.
• Neurologic manifestations: These are the leading cause of morbidity and mortality in patients with TS. Brain hamartomas in the form of cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas are often responsible for intractable seizures, most commonly as infantile spasms. Approximately 90% to 96% of TS patients suffer from seizures. Approximately 85% of patients have their first epileptic episode in the first 2 yr of life. Behavioral and cognitive dysfunction, including autism and mental retardation, can be seen in 40% to 50% of patients.
• Renal and pulmonary manifestations are strongly associated with TS.
• Angiomyolipoma is the most common renal lesion found in TS patients. Clinically evident pulmonary involvement in TS patients is relatively rare, with an estimated incidence of 1% to 6%. The most common lesion is lymphangiomyomatosis (LAM), a progressive cystic lung disease with progressive dyspnea and spontaneous pneumothorax in a childbearing woman.
• Cardiovascular manifestations: These are often the earliest diagnostic findings in patients with TS. Rhabdomyoma is the most common primary cardiac tumor in infants and children. Its incidence in TS patients ranges between 47% and 60%. In fact, 80% to 95% of patients with cardiac rhabdomyomas have TS.
• The most common ocular findings in TS are retinal hamartomas, appearing in 40% to 50% of patients.

DIFFERENTIAL DIAGNOSIS

Cutaneous manifestations:
• Nevus anemicus
• Nevus depigmentosus (nevus achromicus)
• Vitiligo

WORKUP

• The dermatologic manifestations of TS are helpful in diagnosing this disorder. When TS has been inherited in the autosomal dominant form, dermatologic signs are almost universally present in one of the patient’s parents.
• No specific prenatal laboratory test is available.
• Early recognition of TS is vital because prompt implementation of the recommended diagnostic evaluation (neuroimaging studies, EEG, ECG, renal ultrasonography, and chest CT) may prevent serious clinical consequences.

LABORATORY TESTS

• Molecular genetic testing: In recent years, molecular genetic testing for TS has become clinically available. Such testing identifies mutations in the TSC1 and TSC2 genes by one of several methods, most commonly polymerase chain reaction (PCR) amplification of individual exons, followed by DNA sequencing on DNA obtained from a patient’s blood sample.
• DNA testing for TS is potentially useful in several settings:
○ First, it can be helpful in confirming a clinical diagnosis of TS, especially in young patients in whom many clinical signs and symptoms have yet to develop.
○ Second, in many families with a history of TS in which there is a sporadic case of TS in a new child, genetic testing can provide reassurance to parents, children, and other family members that they do not carry the TS gene mutation.
○ Third, DNA testing is useful for prenatal diagnosis.

TREATMENT

The management of TS complex (TSC) is presently symptomatic.

NONPHARMACOLOGIC THERAPY

Genetic counseling should be offered to families with affected members, even though accurate counseling remains difficult because of the variability of gene expression.

ACUTE GENERAL Rx & CHRONIC Rx

• Treatment methods currently available for patients with disfiguring facial angiofibromas include cryosurgery, curettage, dermabrasion, chemical peeling, excision, and laser therapy.
• Some patients have been treated successfully with antiepileptic medications; unfortunately, there are multiple cases of intractable seizure in which medical treatment is ineffective. In some cases of intractable epilepsy, neurosurgical intervention becomes a life-saving option.
• In such drug-resistant cases of TS, the early administration of vigabatrin (a-vinyl-gamma aminobutyric acid), a selective irreversible inhibitor of GABA-transaminase, has been proven to result in 80% to 100% cessation rates of infantile spasms. Vigabatrin is marketed in many European countries, but remains unavailable in the U.S. and has not been approved by the FDA.
• Embolization and/or renal sparing surgery are treatment options for renal angiomyolipomas.
• Oopherectomy, medroxyprogesterone, and tamoxifen use have been advocated in patients with LAM, but therapeutic benefit is unclear. Lung transplantation is reserved for patients with end-stage LAM.
• Most rhabdomyomas tend to regress with increasing age, although tumor growth has been documented in some at puberty. Surgery is recommended only for life-threatening situations, such as hemodynamic compromise.
• Oral rapamycin or sirolimus therapy can induce regression of brain astrocytomas associated with TS. Ongoing therapeutic trials with rapamycin in lymphangioleiomyomatosis appear promising.

Reference : Ferri: Ferri's Clinical Advisor 2011, 1st ed.

SUGGESTED READINGS

Bissler JJ, et al: Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 2008; 358:140-151.

Crino PB, et al: The tuberous sclerosis complex. N Engl J Med 2006; 355:1345-1356.

Hurst JS, Wilcoski S: Recognizing an index case of tuberous sclerosis. Am Fam Physician 2001; 61(3):703-708.

Schwartz RA: Tuberous sclerosis complex. advances in diagnosis, genetics, and managementJ Am Acad Dermatology 2007; 57(2):189-202.