Pseudohypoparathyroidism (PHP) is a disorder associated with a deficiency of stimulatory guanine nucleotide binding protein (Gsa) activity. Albright Hereditary Osteodystrophy (AHO) is a rare autosomal dominant syndrome characterized by short stature, obesity, round face, subcutaneous calcifications, brachymetaphalangism, and variable mental retardation. Patients with PHP type 1a have AHO with resistance to parathyroid hormone and other hormones acting via cAMP. The presence of Albright's syndrome with a normal response to PTH is called Pseudopseudohypoparathyroidism (PPHP).
We report on a 4 year old boy with a strong family history of PHP and PPHP. At 3 weeks of age subcutaneous ossifications were noted in several locations and have since appeared on both feet, arms, legs, thighs and genital region. His early development was notably delayed in language and motor skills. He was diagnosed with PHP 1a at several weeks of age. Presently he manifests distinct features of PHP and AHO- short stature, mental retardation, increased weight, short fourth metacarpals bilaterally, hypothyroidism, pseudohypoparathyroidism, cutaneous heterotopic ossifications, characteristic initial low serum calcium and elevated serum phosphate compatible with PHP 1a. His mother has evidence of mild PPHP with minimal manifestations (subcutaneous ossification around the ankles) and his grandfather may have had similar findings. This case shows characteristic full expression of the gene (AHO + hormone resistance, PHP) transmitted maternally and partial expression (AHO alone) when the gene is inherited from the father, suggesting the involvement of genetic imprinting in the expression of the disorder.
