subcutaneous ossification

Pseudohypoparathyroidism, Type 1A

Clinical Characteristics
Ocular Features: 

Cataracts and nystagmus are sometimes present.  Optic neuritis and papilledema have been reported and can result in optic atrophy.  The combination of cataracts and swelling of the optic nerves in children requires evaluation for hypocalcemia.

Systemic Features: 

The title refers to a group of conditions that have organ resistance to parathyroid hormone.  The phenotype is variable since there usually is a usually some degree of end-organ resistance to other hormones such as gonadotropins and TSH as in the PHP1A disorder described here.  The grouped clinical features are often referred to as Albright hereditary oseodystrophy or AHO.

Short stature with a short neck, a round face, chubby cheeks, and a depressed nasal bridge are usually present.  There may be cognitive deficits and some patients are considered to be mentally retarded.  The fourth and fifth metacarpals and sometimes metatarsals are characteristically short.   The teeth are late to erupt and can have an enamel deficit.  End organ resistance to other hormones may lead to signs of hypothyroidism and hypogonadism.  Calcification of subcutaneous tissues can result in palpable hard nodules and calcium deposition in basal ganglia and choroidal plexus may be demonstrable.  Some patients experience hypocalcemic tetany and seizures.  Hypocalcemia and hyperphosphatemia are often present along with elevated serum parathyroid hormone levels.

Genetics

This transmission pattern is likely modified by the effects of imprinting which also can modify the phenotype.  Mutltigenerational family patterns have an excess of maternal transmission.  The full phenotype is more likely expressed among maternally transmitted cases whereas partial or incomplete expression is more often seen among individuals who received the paternal allele. 

Heterozygous muttions in the GNAS1 gene (20q13.32) plays a role in this disease.  Signal transduction failure likely plays a major role in the failure of organs to respond to the appropriate hormone.

Several subtypes of pseudohypoparathyroidism have been reported but some do not have ocular signs.  However, type 1C (612462) patients can have cataracts and nystagmus with an almost identical phenotype to that of IA and may be the same condition.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Treatment focuses on normalization of calcium and phosphate serum levels.  A deficiency of vitamin D should also be corrected and has been reported to correct at least some of the lens opacities.  Cataract removal can be considered.

References
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