McCune-Albright Syndrome is a rare genetic condition in which skin, endocrine tissues and bones get affected. It causes abnormal scarring of bone tissues, often leading to deformation and fractures. McCune-Albright syndrome further causes patchy skin and abnormal production of hormones leading to early puberty. The condition arises due to genetic mutation, which is random and not inherited by parents.
What is McCune-Albright Syndrome?
McCune-Albright Syndrome is an uncommon disease, which is a consequence of random genetic mutation. The condition is characterized by three features, which are pigmentation of skin, abnormal endocrine hormone production and bone abnormalities. The mutation occurs after fertilization, in the early developmental phase of the embryo and does not affect all the patient's cells instead only a subset. The mutation of GANS1 gene is responsible for the condition, which synthesizes abnormal proteins which further causes abnormalities in cellular functions like cell proliferation, movement and viability.
Symptoms of McCune-Albright Syndrome
The symptoms of McCune-Albright syndrome that help in diagnosis of the condition are:
- Early puberty in girls
- Bone deformity
- Bone fractures
- Irregular and skin pigmentation, more on the back of the body
- Facial asymmetry
- Bone pain due to replacement of bone with fibrous tissue
- Discharge from breasts.
Epidemiology of McCune-Albright Syndrome
The incidences of McCune-Albright syndrome are from one in hundred thousand to one in a million. Amongst the ailing patients, around seventy percent cases suffer from fibrous dysplasia of bone tissues. Apart from fibrous dysplasia, another condition common is precocious puberty, which is more common in females.
Prognosis of McCune-Albright Syndrome
The prognosis or outlook for McCune-Albright syndrome is relatively normal, as the rate of mortality is quite low for the condition. The morbidity for the condition is associated greatly with abnormalities in the bone and abnormal hormone production.
Causes of McCune-Albright Syndrome
McCune-Albright syndrome is the result of genetic mutation in GNAS1 gene. The reason behind the mutation is unknown, but the mutation results in abnormal functioning of pituitary glands, thyroid, ovaries and adrenal glands.
Pathophysiology of McCune-Albright Syndrome
The pathophysiology associated with McCune-Albright syndrome is due to the post zygotic mutation of activated GNAS1 gene. The mutation results in overproduction of variety of hormones which hamper the normal functioning of the body. Some such conditions are:
- Precocious Puberty as a Result of McCune-Albright Syndrome: It is the most prominent feature of McCune-Albright syndrome, in which the ovaries and testicles perform a gonadotropin independent autonomous function. This further result in synthesis of excess of estrogen and testosterone leading to early puberty.
- Café-au-lait Spots due to McCune-Albright Syndrome: These spots arise due to hyperpigmentation in the basal layer of the skin.
- Fibrous Dysplasia as an Outcome of McCune-Albright Syndrome: It marks the small areas on the bones with small lesions that cause disfiguring and fractures of bones.
- McCune-Albright Syndrome Causing Cushing Syndrome: It results due to hyperactivity of adrenal gland leading to elevated levels of cortisone. This further causes weight gain around face as well as mid-section and weight loss in arms and legs.
- Gigantism as a Result of McCune-Albright Syndrome: It occurs due to excess of growth hormone within the body.
- Hyperthyroidism due to McCune-Albright Syndrome: The excess of thyroid synthesis due to over activated thyroid glands leads to hyperthyroidism.
Risk Factors in McCune-Albright Syndrome
There are no specific risk factors associated to the condition; it happens due to the occurrence of random mutation within the zygote just after the fertilization.
Complications of McCune-Albright Syndrome
The complications that may arise due to McCune-Albright Syndrome are:
- Recurrent fractures
- Bone tumors and cancers
- Premature puberty
- Bone deformation
- Loss of sight
- Loss of hearing ability
- Breast cancer in females
- Testicular cancer in males.
Diagnosis of McCune-Albright Syndrome
The identification of McCune-Albright Syndrome can usually be done at birth due to visible symptoms of patchy skin pigmentation and bone deformities. However, in some cases, the condition is identified later as the symptoms get pronounced later. The available diagnostic procedures are:
- Physical Examination to Diagnose McCune-Albright Syndrome: The physical examination involves analysis of symptoms that mark the presence of McCune-Albright Syndrome.
- Blood Tests to Identify McCune-Albright Syndrome: Blood tests are conducted to check for elevated level of endocrine hormones like estrogen, prolactin, growth hormone, testosterone, cortisone and thyroid hormone. It also checks for over activity in the bones.
- X-Rays/ MRI/ CT scan: The specialized imaging techniques are opted to check for the abnormalities in the bones like bone lesions, deformations, tumors and fibrous dysplasia.
- Bone Scan: The bone scan involves injecting radioactive dye within the bones and tracing it to check for bone diseases and their severity.
- Bone Biopsy: The procedure involves surgical extraction of bone tissue followed by microscopic analysis of the bone for abnormalities and diseases.
- Genetic Tests: The detection of genetic mutations of GNAS1 gene can be done through genetic tests. The procedure utilizes PCR or polymerase chain reaction, to amplify the amount of sample extracted from the patient. Further the sample undergoes clinical diagnosis to check for the diagnosis.
How is McCune-Albright Syndrome Treated?
There are no available treatments to treat the condition but there are treatments available to control the symptoms that come up as a result of McCune-Albright Syndrome. The commonly used treatments are:
- Pain Medication for McCune-Albright Syndrome: Administration of pain medication to control the pain that may arise due to bone diseases.
- Bisphosphonates: The bisphosphonates are prescribed to the McCune-Albright Syndrome patients in order to increase the bone density and control fibrous dysplasia.
- Calcium and Vitamin D Supplements to Manage Symptoms of McCune-Albright Syndrome: Additional calcium and vitamin D supplements are prescribed to the patients to reduce the chances of fractures and rickets.
- Hormone Therapy: McCune-Albright Syndrome patients are also given hormone therapy to control the elevated levels of estrogen, testosterone, growth hormone, thyroid hormone and cortisone.
- Physiotherapy to Manage McCune-Albright Syndrome: Physiotherapy is given to McCune-Albright Syndrome patients who have difficulty in moving joints. It helps in maintaining the mobility and strength of the joints.
- Surgical Procedures for McCune-Albright Syndrome: Surgical procedures are done to provide support to the bones through grafts and fixators. Other than bones, surgeries are also performed to remove ovarian cysts and abnormal adrenal glands.
McCune-Albright syndrome is a disease of rare occurrence, which is known to target skin, bones and endocrine system. The primary characteristics of McCune-Albright Syndrome include abnormal skin pigmentation, dysfunctional endocrinal glands and fibrous dysplasia of bones. Apart from fibrous dysplasia, either of the other two symptoms should be present to confirm the presence of McCune-Albright Syndrome. The endocrine dysfunction can range from early sexual development, gigantism, hyperthyroidism, bone abnormalities to hepatic dysfunction. McCune-Albright Syndrome arises due to genetic mutation of GNAS1 gene, the cause of which remains unknown. The extent of mutation varies from individual to individual; therefore, the symptoms too vary greatly. Thus, the treatment of the condition focuses on dealing with the symptoms as there is no treatment available for McCune-Albright Syndrome.