Cutaneous Ossification in Albright’s Hereditary Osteodystrophy

Abstract

A 23-year-old woman presented with subcutaneous ossification, which together with short stature, stocky physique, round face and brachydactyly suggested Albright’s hereditary osteodystrophy (AHO). Serum calcium and phosphorus levels were normal. AHO refers to the phenotype of the syndromes of pseudohypoparathyroidism (PHP) type la and pseudopseudohypoparathyroidism (PPHP), both considered genetically related variants with a defect of the α sub-unit of the stimulatory G protein of adenylate cyclase necessary for the action of parathyroid and other hormones using cyclic AMP as an intracellular second messenger. PPHP differs from PHP in that it lacks parathyroid hormone resistance manifesting itself as hypocalcemia. Other endocrine end organ unresponsiveness, e.g. hypothyroidism and hypogonadism, may also be found with PHP. Both PHP and PPHP usually exhibit characteristic phenotypic abnormalities, of which subcutaneous ossification may be a presenting feature. The differential diagnosis of cutaneous calcification and ossification is outlined.

Clinical and Biological Heterogeneity in Pseudohypoparathyroidism Syndrome

“…Three mothers of these patients had only isolated subcutaneous calcification [24], Gsa defect and AHO transmission were often but not always linked (i.e., families 20,28) and were differently expressed in sib lings regardless of sex. However, the distribution of AHO or biochemical abnormalities within families 11-25 is consistent with an increased severity of PHP through each successive generation.…”

Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification

“…Over time, ectopic ossifications lead to ankylosis of affected joints and growth retardation of affected limbs. By contrast, ectopic bone in AHO presents later in life and is largely restricted to cutaneous and subcutaneous tissue 6 . POH and AHO are caused by inactivating mutations in GNAS 4,5,7,8 , which encodes Gα s that transduces signals from G protein coupled receptors (GPCRs).…”

Osteoma Cutis as the Presenting Feature of Albright Hereditary Osteodystrophy Associated with Pseudopseudohypoparathyroidism

“…Therefore, it provides a potential explanation for the development of ectopic bone in patients with Albright's hereditary osteodystrophy associated with PHP-Ia and PPHP. Osteoma cutis and obesity are observed less frequently in patients with PPHP than in those patients with PHP 7,11 . The frequency of osteoma cutis in patients with PPHP is unknown.…”

“…Some AHO patients have mental retardation. Osteoma cutis mostly appears in the periarticular regions such as the scalp, and particularly the hands and feet, but it can occur anywhere in the body 7 . The ossification is usually not progressive or painful.…”