P. A. Rejini
Deputy Nursing Officer, SRI Ramakrishna Hospital, Coimbatore – 44.
*Corresponding Author Email: kodaimeena@gmail.com
ABSTRACT:
McCune-Albright syndrome is a rare and challenging congenital sporadic disease involving the skin and skeletal and endocrine systems. In addition to the classical triad of fibrous dysplasia of bone, café au lait pigmented skin lesions and precocious puberty, other multiple endocrinological features, including hyperthyroidism, growth hormone excess, hypercortisolism, and hypophosphatemic rickets, have been reported. A brief review of the syndrome in children is here reported.
KEYWORDS: McCune–Albright syndrome, Endocrinopathies, Precocious puberty café au lait skin pigmentation, Fibrous dysplasia of bone.
INTRODUCTION:
It was first described in 1937 by American pediatrician Donovan James McCune and American endocrinologist Fuller Albright.3,4,5 McCune-Albright syndrome is a rare genetic disordered originally recognized by the triad of polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots. McCune-Albright syndrome is a disorder that affects the bones, skin, and several hormone-producing (endocrine) tissues. A variety of endocrine disorders, including hyperthyroidism, acromegaly, phosphate wasting, and Cushing syndrome are now considered as part of the endocrinopathies seen in this disorder. The variable constellation of symptoms arises from a somatic activating mutation of the GNAS gene, which is present in many tissue types.1
Definition:
McCune–Albright syndrome is a complex genetic disorder affecting the bone, skin and endocrine systems. It is a mosaic disease arising from somatic activating mutations in GNAS, which encodes the alpha-subunit of the Gs heterotrimeric G protein.2
Incidence:
McCune–Albright syndrome is estimated to occur at a frequency between 1 person in 100,000 to 1 person in 1,000,000 individuals worldwide.6
Terminology:
1. Polyostotic fibrous dysplasia:
Polyostotic fibrous dysplasia is a form of fibrous dysplasia affecting more than one bone. Fibrous dysplasia is a disorder where bone is replaced by fibrous tissue, leading to weak bones, uneven growth, and deformity36.
2. Café au lait spots, or café au lait macules:
These are flat, hyper pigmented birthmarks.7 The name café au lait is French for "coffee with milk" and refers to their light-brown color. Café au lait lesions with rough borders (“coast of Maine”)50
3. Precocious puberty:
(PP) is defined as the development of pubertal changes, at an age younger than the accepted lower limits for age of onset of puberty, namely, before age 8 years in girls and 9 years in boys. In a minority of children with precocious puberty, the early development is triggered by a disease such as a tumor or injury of the brain.
Other Name:
Albright syndrome, MAS, osteitis fibrosa disseminate, PFD, POFD, polyostotic, fibrous dysplasia, precocious puberty with polyostotic fibrosis and abnormal pigmentation.23,24,25.
Differential diagnosis:
Neurofibromatosis,44 osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty49, and ovarian neoplasm.
Etiology:
The cause of McCune-Albright syndrome is a spontaneous post zygotic missense mutation at ARG201 or Gln227 of the GNAS gene during embryogenesis.39 GNAS encodes the alpha subunit portion of a G-signaling complex that found in multiple tissue types, including bone, skin, and endocrine tissues. The mutation is distributed in a mosaic pattern and presenting signs and symptoms are dependent on the time frame the mutation occurs. Mutated GNAS results in a constitutively active alpha subunit, causing increased intracellular cAMP, and mediating the action of downstream hormones.8
Pathophysiology:35
· Constitutively active mutant GNAS results in increased cyclic adenosine monophosphate, which
· Promotes proliferation and inhibits differentiation of fibroblasts, which replace normal bone, producing fibrous dysplasia lesions Promotes proliferation and autonomous function of endocrine organs
· Fibrous dysplasia elaborates fibroblast growth factor 23, which
· Inhibits renal resorption of phosphate
· Causes hypophosphatemia
· Causes hyperphosphaturia
· Examples:
· Unregulated production of cortisol leading to Cushing syndrome
· Unregulated production of gonadotropin releasing hormone leading to precocious puberty.
Signs and Symptoms:
McCune–Albright syndrome is suspected when two or more of the following features are present:
2. Hyper pigmented skin lesions with characteristic features, including jagged "coast of Maine" borders and tendency occur along the midline of the body. These lesions are historically termed café au lait macules, however the term "cafe-au-lait" only describes their appearance on lighter-skinned individuals.9
3. Hyper functioning endocrine disease
Patients may have one or many of above features, which may occur in any combination.10
Various endocrine diseases may present in McCune–Albright syndrome due to increased hormone production.
This is the most common endocrinopathy which is seen in girls (~85%) with recurrent estrogen-producing cysts leading to episodic breast development, growth acceleration, and vaginal bleeding.11,12 Precocious puberty may also occur in boys with McCune–Albright syndrome, but is much less common (~10–15%).12 In children of both sexes, growth acceleration may lead to tall stature in childhood, however premature bone maturation may lead to early growth plate fusion and short stature in adulthood.42
· Testicular abnormalities:
Testicular abnormalities are seen in a majority (~85%) of boys with McCune–Albright syndrome.12,13,14 These typically present with macro-orchidism.
· Hyperthyroidism: Hyperthyroidism occurs in approximately one-third of patients with McCune Albright syndrome. Patients have characteristic abnormalities on thyroid ultrasound, and may have a slight increased risk for thyroid cancer.12,13,14
· Growth hormone excess: Excess growth hormone secretion and is found in approximately 10–15% of patients.12 This may lead to expansion of craniofacial fibrous dysplasia, increasing the risk of vision and hearing loss.15,16
· Cushing's syndrome: In McCune–Albright syndrome, Cushing's syndrome is a very rare feature that develops only in infancy.17
· Hypophosphatemia due to increased fibroblast growth factor 23 production may lead to rickets, osteomalacia, and worsening skeletal outcomes.18
Diagnosis:
McCune–Albright syndrome has different levels of severity. Diagnosis may be made only after decades when child with McCune–Albright syndrome may be entirely healthy, with no outward evidence of bone or endocrine problems, with symptoms diagnosed are done in early infancy, show obvious bone disease, and obvious increased endocrine secretions from several glands.
a) CT scan of the skull: to evaluate craniofacial fibrous dysplasia.38
b) Regular hearing and vision screening
c) X-rays to reveal fibrous dysplasia of the appendicular skeleton. Radiographs reveal a characteristic lesion of thinning cortex and intramedullary “ground glass.”31
d) CT and/or MRI scans to reveal micro fractures.38
e) Regular screening for scoliosis .
f) Nuclear medicine tests such as technetium-99 scintigraphy are done to detect fibrous dysplasia lesions.19
1. A bone age examination shall be performed to evaluate skeletal maturation.
2. Boys and men should have a screening testicular ultrasound.20
3. Hyperthyroidism is diagnosed based on blood tests.
4. A screening thyroid ultrasound exam may be performed.20
5. Growth hormone excess is diagnosed using blood tests, such as insulin-like growth factor-1 levels.20
6. Blood phosphorus levels for Hypophosphatemia.20
7. Cushing syndrome is very rare, and is typically diagnosed clinically in infants who present with signs of severe illness.20
Treatment:
a. Gonadotropin-independent precocious puberty - Aromatase inhibitors
b. Development of central precocious puberty-steady-state gonadotropin-releasing hormone analogs are used to down regulate hypothalamic-pituitary-gonadal axis.26,27,28
c. Treatment of hyperthyroidism is initially managed medically with ant thyroid medications and radio ablation.41
d. Growth hormone excess treatment is by somatostatin or direct GH receptor antagonists.
e. Hyperprolactinemia management is with bromocriptine.
f. In pituitary adenomas- surgical resection of the adenoma is an option.
g. No definitive guidelines for surgical intervention of fibrous dysplastic lesions exist. However, common indications for surgical stabilization include progression of pain, stress fracture, deformity, or loss of function.
h. Studies investigating the use of high dose bisphosphonates show mixed results, and currently, the only indication for bisphosphonate therapy is pain relief.42
i. Surgical intervention due to cranial-facial lesions may be necessary when there is a potential for loss or sight or hearing.
j. Screening and management of endocrinopathies is an important part of managing fibrous dysplasia. For example, untreated growth hormone excess increases the risk of craniofacial fibrous dysplasia expansion and may lead to vision loss.32
k. Oral phosphate and calcitriol may be given for treatment of hypophosphatemia.33
Prognosis:
Prognosis may be challenging to ascertain due to the varying severity of the disease. Younger patients with renal phosphate wasting and polyostotic lesions have a higher risk of clinically relevant bone pain and fracture.46
The primary treatment goal of precocious puberty is the preservation of potential adult height. Without intervention, growth plates close prematurely resulting in short stature.47
While rare, there is potential for malignant transformation of fibrous dysplastic lesions.48 There are also reports of increased breast cancer risk.1
Complication: 40
1. Brittle, warped bones (osteoporosis)
2. Repeated fractures.
3. Rickets.
4. Blindness or deafness due to abnormal growth of skull bones.
5. Adrenal gland tumours.
6. Osteitis fibrosa cystica – soft bones that are prone to developing cysts
7. Premature puberty
8. Repeated broken bones
9. Tumors of the bone (rare)
10. Decreased adult stature is the main complication of untreated precocious puberty.45
These best practice guidelines have been developed by an international collaboration between multiple clinical specialities, patients and patient advocacy groups, using the best evidence available. The FD/MAS guidelines are intended to improve the clinical care of patients across the world by addressing diagnosis, staging, treatment and monitoring aspects of their care given the potential serious risks to patient outcomes with late diagnosis The provision of a Patient Checklist See Additional file Fibrous Dysplasia and McCune-Albright Syndrome: A Checklist of Patients and Doctors) is aimed at informing and empowering patients to seek excellence of healthcare for their disease. Describing standards across the clinical care pathway enables clinical services to be audited, helps in the identification of areas of the patient pathway that require service improvement and facilitates cross-border sharing of best clinical practice between clinical services in different countries.
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Received on 09.03.2022 Modified on 22.04.2022
Accepted on 19.05.2022 ©A&V Publications All right reserved
Asian J. Nursing Education and Research. 2022; 12(3):356-360.
DOI: 10.52711/2349-2996.2022.00075