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Syndromes: Rapid Recognition and Perioperative Implications, 2e

McCune­Albright Syndrome

At a glance
It is characterized by the triad of polyostotic fibrous dysplasia, café­au­lait skin pigmentation, and autonomous endocrine hyperfunction. The most
common form of autonomous endocrine hyperfunction is gonadotropin­independent precocious puberty, but affected individuals also may have
hyperparathyroidism, hyperthyroidism Cushing’s disease, hypercorticism, hyperprolactinemia, pituitary gigantism, or acromegaly. Nonendocrine
abnormalities in this disorder include chronic liver disease, tachycardia, and rarely sudden death as a result of cardiac arrhythmias.

Synonyms
Polyostotic Fibrous Dysplasia; Osteitis Fibrosa Cystica; McCune Syndrome; Albright Syndrome; Osteitis Fibrosa Disseminata; Precocious Puberty
Independent Gonodotropins in Girls.

History
Genetic disorder first described in 1936 by Donovan James McCune, an American pediatrician, and then in 1937 by Fuller Albright, an American
physician. The disease made the US headlines in December 2005 when a Haitian teen affected with the disease, Marlie Casseus, underwent a 17­hour
surgical procedure to remove a very large bone tumor­like growth from her face.

Incidence
The exact incidence remains unknown. It seems more common in females.

Genetic inheritance
Autosomal dominant lethal mosaic postzygotic somatic mutation in the GNAS 1 gene located on chromosome 20q13.2.

Pathophysiology
Described as a mosaicism for a mutation in the gene encoding the subunit of the G protein stimulating cyclic adenosine monophosphate (cAMP)
formation. This results in activation of various cAMP­dependent receptors including adrenocorticotropic hormone (ACTH), thyroid­stimulating
hormone (TSH), follicle­stimulating hormone (FSH), and luteinizing hormone (LH) receptors leading to autonomous and aberrant behavior toward
otherwise normal stimuli.

Clinical aspects
Classic triad of endocrine dysfunction, bone lesions, and pigmented skin lesions. Average age of onset is 3 years. Precocious pseudopuberty (F >M);
vaginal bleeding may begin as early as age 4 months and secondary sexual characteristics as early as 6 months. Acromegaly (F = M). Cushing Syndrome
may occur in early infancy before onset of precocious pseudopuberty and is associated with adrenocortical hyperplasia. The presence of a
multinodular goiter (M = F) and hyperthyroidism is reported in 20 to 40% of patients. The associated pathologic fractures and deformities of long
bones result from hypophosphatemic osteomalacia. Shepherd crook deformity of the proximal femur is particularly characteristic, and bony lesions in
the base of skull may result in cranial nerve compression, blindness, and deafness. Large, patchy cutaneous pigmentation with irregular margins on
neck, face, back, and shoulders are found in approximately 90% of children with this syndrome. Both the bony and skin lesions are limited
predominantly to one side.
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McCune­Albright
McCune–Albright Syndrome, Page 1 / 3
Syndrome: Cushing­like habitus and “café­au­lait” spots giving particular skin pigmentation in a small girl with McCune­Albright
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Syndrome. Note precocious breast development.
may occur in early infancy before onset of precocious pseudopuberty and is associated with adrenocortical hyperplasia. The presence of a
Boston
multinodular goiter (M = F) and hyperthyroidism is reported in 20 to 40% of patients. The associated pathologic fractures and Children’s
deformities Hospital
of long
bones result from hypophosphatemic osteomalacia. Shepherd crook deformity of the proximal femur is particularly characteristic, and bony lesions in
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the base of skull may result in cranial nerve compression, blindness, and deafness. Large, patchy cutaneous pigmentation with irregular margins on
neck, face, back, and shoulders are found in approximately 90% of children with this syndrome. Both the bony and skin lesions are limited
predominantly to one side.

McCune–Albright Syndrome: Cushing­like habitus and “café­au­lait” spots giving particular skin pigmentation in a small girl with McCune­Albright
Syndrome. Note precocious breast development.

Diagnosis
Clinical features of endocrine abnormalities, café­au­lait spots, and polyostotic fibrous dysplasia. Biochemical: Thyroid (mildly elevated T3, low TSH);
adrenal (raised cortisol and low ACTH levels, adrenal function not suppressed by dexamethasone); pituitary (elevated growth hormone and prolactin
levels); hypophosphatemia as a result of decreased resorption of phosphate in the renal tubule; ovaries (estradiol varies from normal to markedly
elevated levels, suppressed levels of LH and FSH, no response to luteinizing hormone­releasing hormone stimulation). Imaging studies:
Ultrasonography (ovarian cysts, nodular adrenal hyperplasia); skeletal radiography (widespread cystic bony lesions, advanced bone age, fractures and
deformities of long bones, bony lesions in base of skull).

Anesthetic considerations
Direct laryngoscopy and tracheal intubation may be difficult in the presence of acromegaly. Possibility of airway compression and tracheomalacia must
be considered with long­standing multinodular goiter. Hyperthyroidism, if present, should be controlled before anesthesia to avoid thyroid storm
crisis. Cushing Syndrome requires preoperative correction of hypokalemia. Intraoperative monitoring and control of blood sugar levels, hypertension,
and/or heart failure must be managed accordingly. Venous access may be difficult because of fragility of veins.

Pharmacological implications
Supplementation corticosteroids must be considered preoperatively. All supplemental endocrinologic medication must be administered.

Other conditions to be considered

Acromegaly and Gigantism: Gigantism is extremely rare in the United States, with approximately 100 reported cases. Acromegaly is found more
frequently, with an incidence of 3 to 4:1,000,000 people per year and a prevalence of 40 to 70:1,000,000 population. It is associated with chronic
exposure to excessive growth hormone production and clinically characterized with overgrowth of the extremities in adulthood.

☞Cherubism: Characterized by bilateral displacement of normal bone tissue with areas of fibrous dysplasia within the maxilla and mandible.
Clinical presentation
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A Your swelling of the face, “upturning” of the eyes, café­au­lait spots, and/or significant nevi. Age of onset is usually
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between the third
McCune­Albright and fourth year of life. It is inherited as an autosomal dominant trait with variable expressivity and penetrance. One hundred
Syndrome, Page 2 / 3
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of females have signs of the disease (reduced penetrance).

☞Albright Hereditary Osteodystrophy: Syndrome presenting with round face, short stature, short neck, and obesity. Other features include
 Acromegaly and Gigantism: Gigantism is extremely rare in the United States, with approximately 100 reported cases. Acromegaly is found more
Boston Children’s Hospital
frequently, with an incidence of 3 to 4:1,000,000 people per year and a prevalence of 40 to 70:1,000,000 population. It is associated with chronic
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exposure to excessive growth hormone production and clinically characterized with overgrowth of the extremities in adulthood.

☞Cherubism: Characterized by bilateral displacement of normal bone tissue with areas of fibrous dysplasia within the maxilla and mandible.
Clinical presentation includes swelling of the face, “upturning” of the eyes, café­au­lait spots, and/or significant nevi. Age of onset is usually
between the third and fourth year of life. It is inherited as an autosomal dominant trait with variable expressivity and penetrance. One hundred
percent of males are fully affected (high penetrance), whereas 50 to 75% of females have signs of the disease (reduced penetrance).

☞Albright Hereditary Osteodystrophy: Syndrome presenting with round face, short stature, short neck, and obesity. Other features include
subcutaneous and intracranial calcifications, seizures, and neuromuscular problems such as fatigue and muscle cramps. Clinically, the
association of pseudohypoparathyroidism and hypocalcemia is often reported.

Fibrous Dysplasia (FD): Rare bone disorder characterized by the presence of polyostotic disease, particularly the craniofacial and the ribs are
most often affected. The onset of symptoms is usually diagnosed in children or young adults.

Neurofibromatosis Type 1: Rare genetic disorder characterized by the presence of “cafe­au­lait” spots, particularly located in the axillary and
inguinal areas, iris Lisch nodules, and slow­growing tumors of the optic nerve. Other clinical features include macrocephaly, ocular hypertelorism,
short stature, and scoliosis. Neurofibromatosis type 1 is an autosomal dominant disorder.

Moreno Nishimura Schmidt Overgrowth Syndrome (Moreno Nishimura Schmidt Syndrome; Nishimura Schmidt Endochondral
Gigantism Syndrome; Endochondral Gigantism Syndrome): Rare medical condition characterized by pre­ and postnatal gigantism that is
believed due to excessive growth of the endochondral bone. The clinical features include facial dysmorphism (narrow skull, prominent
supraorbital arches, enlarged ears, micrognathism), thoracic anomalies (kyphoscoliosis, elongated chest), skeletal anomalies (enlarged hands
and feet, joint contractures, thickening of the base of the skull), hoarseness, and endocrine dysfunctions (particularly slow response to cortisol
secretion to insulin). Although there is no known report of anesthesia complications, one may expect an increased risk of difficult intubation and
laryngoscopy (micrognathia), and the presence of hoarseness. A suspicion of slow adrenocortical response to surgical stress must be kept in
mind. Intraoperative supplementation of cortisol in presence of unexplained hypotension should be considered.

References

DiMeglio LA, Pescovitz OH: Disorders of puberty: Inactivating and activating molecular mutations. J Pediatr 131:S8, 1997. [PubMed: 9255219]

Handa A, Muroya K, Ishii T, Nishimura G: Additional report on Moreno­Nishimura­Schmidt overgrowth syndrome. Am J Med Genet A 173(10):2834–
2837, 2017. [PubMed: 28742279]

Happle R: The McCune­Albright syndrome: A lethal gene surviving by mosaicism. Clin Genet 29:321, 1986. [PubMed: 3720010]

Kang S, Jeong J: Anesthetic consideration of a patient with McCune­Albright syndrome: A case report. Open Journal of Anesthesiology 6:187–192,
2016.

Langer RA, Yook I, Capan LM: Anesthetic considerations in McCune­Albright syndrome: Case report with literature review. Anesth Analg 80:1236,
1995. [PubMed: 7762858]

Torigoe K, Akioka K, Kaneko Y, Kobayashi Y, Shiratori R: Anesthetic management of a patient with McCune­Albright syndrome accompanied by
polyostotic fibrous osteodysplasia. J Anesth 15(2):108–110, 2001. [PubMed: 14566534]

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