Clinical Presentation

A child presents with mild developmental delay and marked shortening of the fourth and fifth rays of hands and feet.

Figure 119A

Figure 119B

Radiologic Findings

Diagnosis

Pseudohypoparathyroidism (PHP) (Albright hereditary osteodystrophy)

Differential Diagnosis

• Pseudopseudohypoparathyroidism (PPHP)
  
  
  
  • Phenotypically identical to PHP
    
  • Patients with PPHP are normocalcemic.
  
  
• Acrodysostosis
  
• Turner syndrome
  
• Sickle-cell disease
  
• Trauma
  
• Hypoparathyroidism
  
• Cranial radiation therapy
  
• Carbonic anhydrase type 2 deficiency

Discussion

Background

Metacarpal shortening can result from multiple diverse etiologies, including prior infection, trauma, infarction, inflammatory arthritis, skeletal dysplasia, or inborn error of metabolism. Intracranial calcifications may result from hypoxia, hypercalcemia, hypoparathyroidism, radiation therapy, and TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, Herpes) infections, among others. However, the combination of metacarpal shortening and intracranial calcifications is most consistent with the diagnosis of PHP or PPHP.

Etiology

PHP is a rare autosomal dominant condition that consists of refractory hypocalcemia and hyperphosphatemia, unresponsive to parathormone (PTH) therapy. The kidneys in patients with PHP and PPHP are resistant to PTH stimulation; therefore, these patients are hypocalcemic and hyperphosphatemic.

Phenotypic variability is common. There are several distinct subtypes, all due to heterozygous inactivating mutations of GNAS1