Progressive osseous heteroplasia-like heterotopic ossification in a male infant with pseudohypoparathyroidism type Ia: a case report.
Bone 2007; 40(5):1425-8BONE

Abstract

Pseudohypoparathyroidism (PHP) Ia is a rare condition associated with multiple hormone resistance and the Albright Hereditary Osteodystrophy (AHO) phenotype. Progressive osseous heteroplasia (POH) is characterized by progressive ossifications of dermal, skeletal muscle and deep connective tissue during childhood. Both PHP Ia and POH are caused by heterozygous inactivating mutations in the GNAS gene. Maternal inheritance of a GNAS mutation leads to an AHO phenotype with hormonal resistance (PHP Ia), whereas paternal inheritance leads to an AHO phenotype without the hormonal resistance (pseudopseudo-hypoparathyroidism). Pure POH (no other AHO features) is also caused by a paternal inheritance of GNAS mutations. Mutations that cause PHP Ia when maternally inherited can cause POH when paternally inherited. We present an unusual case of a boy with clinical features of both POH and PHP Ia, and a GNAS inactivating mutation.

CASE PRESENTATION

The patient was referred at 1 month of age with a "knot on his leg". Plain radiographs revealed subcutaneous ossifications. PE at age 4 months included: length and weight >95%, a round face, short 4th metacarpals, and extensive subcutaneous ossifications of the lower limbs, buttocks, and back. Studies at age 4 months included an elevated TSH 12.4 mIU/l, free T4 0.86 ng/dl (0.8-2.3), PTH 61 pg/ml (10-65), calcium 9. 8 mg/dl (9.0-11.0), and phosphorus 6. 4 mg/dl (3.8-6.5). By age 16 months, the PTH was elevated at 126 pg/ml. Biopsies of the skin lesions demonstrated osteoma cutis consistent with POH. GNAS analysis revealed a heterozygous deletion in exon 7. The mutation was not detected in either parent.

DISCUSSION

POH and PHP Ia are rare genetic disorders caused by loss of function mutations of the GNAS gene. POH and PHP Ia do not commonly occur in the same individual as they are associated with paternal versus maternal inheritance (imprinting) of an affected GNAS gene. Our patient has evidence of both severe POH and PHP Ia, apparently due to a de novo mutation in GNAS.

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    Authors+Show Affiliations

    Gelfand IM
    Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, Indiana University School of Medicine, James Whitcomb Riley Hospital for Children, Indianapolis, IN, USA. ingelfan@iupui.edu
    Hub RS
    No affiliation info available
    Shore EM
    No affiliation info available
    Kaplan FS
    No affiliation info available
    Dimeglio LA
    No affiliation info available

    MeSH

    BiopsyDisease ProgressionHumansInfantMaleOssification, HeterotopicPseudopseudohypoparathyroidism

    Pub Type(s)

    Case Reports
    Journal Article

    Language

    eng

    PubMed ID

    17321228