Acrodysostosis

Synonyms

4

Overview

Acrodysostosis is a rare congenital malformation syndrome which involves shortening of the interphalangeal joints of the hands and feet, intellectual disability in approximately 90% of affected children, and peculiar facies. Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.  Many individuals with acrodysostosis have developmental delays and intellectual disability. Acrodysostosis can be difficult to distinguish from pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

Most reported cases have been sporadic, but it has been suggested that the condition might be genetically related i.e. in an autosomal dominant mode of transmission. Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception.

Symptoms

  • Frequent middle ear infections
  • Growth problems, short arms and legs
  • Hearing problems
  • Mental deficiency
  • Unusual looking face
  • Abnormal form of the vertebral bodies
  • Abnormality of the metacarpal bones
  • Abnormality of the nail
  • Accelerated skeletal maturation
  • Aplasia/Hypoplasia involving the nose
  • Brachydactyly syndrome
  • Cognitive impairment
  • Cone-shaped epiphysis
  • Depressed nasal bridge
  • Depressed nasal ridge
  • Malar flattening
  • Open mouth
  • Short nose
  • Short stature
  • Short toe

Causes

One form of acrodysostosis, called acrodysostosis with hormonal resistance, is caused by a mutation in the PRKAR1A gene or the PDE4D gene. The underlying cause for other forms of acrodysostosis is unknown. Acrodysostosis appears to have an autosomal dominant inheritance pattern, with most reported cases occurring for the first time in a family due to a new mutation. Inheritance from an affected parent has been described as well.

It is mention in the literature that these gene mutations are occured as a new (sporadic or de novo) mutations. It means that gene mutation has been occurred at the time of the formation of the egg or sperm for that child and no other family member will be affected. The disorder is usually not inherited from or "carried" by a healthy parent. However, dominant inheritance (where a trait is transmitted from either an affected mother or father to their child) has been documented in this disease.

Prevention

Consider genetic counseling to help with diagnosis, testing, and identifying risk.

Diagnosis

  • Detailed patient history
  • Thorough clinical evaluation 
  • Variety of specialized tests including X-rays.
  • Clinical Testing and Workup
  • Prenatal fetal ultrasonography
  • Molecular genetic testing

Prognosis

Problems depend on the degree of skeletal involvement and mental retardation. In general, patients do relatively well.

Treatment

There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Treatment depends on the physical and mental problems that occur. Orthopedic care, early intervention, and special education are recommended.

Resources

  • NIH