Answer
Evaluation of café-au-lait pigmentation requires a detailed family history because neurofibromatosis (NF) also produces multiple café-au-lait spots. Unlike MAS, which occurs sporadically, NF is an autosomal dominant condition. A diagnosis of NF should be considered if a family history of café-au-lait pigmentation is noted, and the possibility should not be discounted even when precocious puberty occurs with café-au-lait spots. Hypothalamic optic gliomas with NF can lead to gonadotropin-dependent precocious puberty.
Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!
Media Gallery
-
Base of the skull computed tomography scan showing extensive fibrous dysplasia in McCune-Albright syndrome. Note the asymmetrical affectation, with near-total obliteration of various neural foramina at the base of the skull. This degree of fibrous dysplasia can result in multiple cranial nerve compression neuropathies, of which blindness and deafness (from involvement of cranial nerves II and VIII) are among the most disabling.
-
Café au lait spot. This is a fairly large, irregular-edged ("coast-of-Maine" variety) lesion. It presents as a brownish, otherwise-asymptomatic macule/patch. The degree of pigmentation is fairly uniform.
-
Fibrous dysplasia of a long bone characterized by focal bony expansion, patchy areas of sclerosis, and bony cyst formation in McCune-Albright syndrome.
-
Plain skull radiograph in a typical McCune-Albright syndrome case shows marked macrocrania, frontal bossing, and markedly thickened bony table in patchy areas, particularly at base of skull and occiput. Skull also shows hair-on-end appearance, which needs to be differentiated from similar radiologic appearances in Paget disease or poorly controlled hemoglobinopathy (eg, beta-thalassemia, sickle cell disease).
-
Large café-au-lait patches around shoulder in child with McCune-Albright syndrome.
-
Lucency characteristic of polyostotic fibrous dysplasia in patient with McCune-Albright syndrome.
-
Café-au-lait pigmentation in case of McCune-Albright syndrome. Lesion does not cross midline, which is typical of pigmented lesions in this syndrome.
-
Adrenal hyperplasia with nodular elements in adrenal gland isolated from infant with infantile Cushing syndrome in the context of McCune-Albright syndrome. DNA isolated from nodular tissue was determined to have activating Gs alpha mutation (GNAS1), whereas DNA isolated from surrounding tissue did not contain this mutation.
-
The G protein cycle begins with ligand binding to a 7-transmembrane domain G protein-coupled receptor (GPCR). Binding of the cognate ligand forms a ligand-receptor complex, which then stimulates an exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the alpha subunit of the stimulatory G protein (Gs alpha). This activates the alpha subunit, which subsequently stimulates adenylyl cyclase (AC) to increase production of cyclic adenosine monophosphate (cAMP). The alpha subunit contains intrinsic guanosine triphosphatase (GTPase) activity, which cleaves a phosphate group from GTP, converting it to GDP, and thus inactivates the alpha subunit. The inactivated alpha subunit is now ready to be reactivated by ligand-receptor binding, so that the next cycle of signal transduction can occur.
-
Mutations in McCune-Albright syndrome inactivate intrinsic guanosine triphosphatase (GTPase) activity, thus preventing inactivation of the "turned-on" Gs alpha subunit. Once activated, the mutated Gs alpha subunit is able to continuously stimulate adenylyl cyclase, even in absence of ligand binding to its cognate GPCR receptor. The result is elevation of intracellular cyclic adenosine monophosphate (cAMP) and continual stimulation of downstream cAMP signaling cascades.
of
10