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Anauxetic dysplasia

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Description

Anauxetic dysplasia is a disorder characterized by extremely short stature (dwarfism) and other skeletal abnormalities, an unusually large range of joint movement (hypermobility), dental problems, and distinctive facial features. Mild intellectual disability can also occur in this disorder.

People with anauxetic dysplasia have dwarfism with unusually short limbs for their height (disproportionate short stature) beginning before birth. Dislocation of the bones at the top of the spine (atlantoaxial subluxation) can also occur in this disorder, and may cause pinching (compression) of the spinal cord. As a result, affected individuals may experience neurological symptoms including pain, tingling, numbness, coordination problems, weakness, and paralysis. In severe cases, the spinal cord compression may lead to paralysis of the muscles needed for breathing, which can be life-threatening during early childhood.

Other skeletal abnormalities in anauxetic dysplasia include a barrel-shaped chest and a rounded upper back that also curves to the side (kyphoscoliosis). Without surgical correction, the kyphoscoliosis can constrict the lungs and cause difficulty breathing. People with anauxetic dysplasia can also have an exaggerated curvature of the lower back (hyperlordosis), dislocation of the hips, and soles of the feet that are rounded outward (rocker-bottom feet).

Typical facial features in anauxetic dysplasia include closely spaced eyes (hypotelorism), a flat or sunken appearance of the middle of the face (midface hypoplasia), an unusually large tongue (macroglossia), and a protruding chin (prognathism). Affected individuals can also have fewer teeth than normal (hypodontia).

Frequency

Anauxetic dysplasia is a very rare disorder; its prevalence is unknown.

Causes

Anauxetic dysplasia can be caused by mutations in the RMRP gene. Unlike many genes, the RMRP gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA, a chemical cousin of DNA, is produced from the RMRP gene. Several proteins attach (bind) to this RNA molecule, forming an enzyme complex called mitochondrial RNA-processing endoribonuclease, or RNase MRP.

The RNase MRP enzyme is thought to be involved in several important functions in the cell, including processing ribosomal RNA. This form of RNA is associated with cell structures called ribosomes, which assemble protein building blocks (amino acids) into proteins.

The RMRP gene mutations that cause anauxetic dysplasia alter the noncoding RNA produced from the gene, and the RNase MRP enzyme containing the altered noncoding RNA is impaired in its ribosomal RNA processing function. Although the specific mechanism is unknown, impairment of this function likely disrupts skeletal development, leading to the signs and symptoms of anauxetic dysplasia.

Mutations in at least one gene that provides instructions for making a protein component of the RNase MRP enzyme complex can also cause anauxetic dysplasia.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

  • AD
  • spondylometaepiphyseal dysplasia, anauxetic type
  • spondylometaepiphyseal dysplasia, Menger type

Additional Information & Resources

Genetic and Rare Diseases Information Center

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Barraza-García J, Rivera-Pedroza CI, Hisado-Oliva A, Belinchón-Martínez A, Sentchordi-Montané L, Duncan EL, Clark GR, Del Pozo A, Ibáñez-Garikano K, Offiah A, Prieto-Matos P, Cormier-Daire V, Heath KE. Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia. Clin Genet. 2017 Jul;92(1):91-98. doi: 10.1111/cge.12964. Epub 2017 Feb 22. Citation on PubMed
  • Elalaoui SC, Laarabi FZ, Mansouri M, Mrani NA, Nishimura G, Sefiani A. Further evidence of POP1 mutations as the cause of anauxetic dysplasia. Am J Med Genet A. 2016 Sep;170(9):2462-5. doi: 10.1002/ajmg.a.37839. Epub 2016 Jul 6. Citation on PubMed
  • Glazov EA, Zankl A, Donskoi M, Kenna TJ, Thomas GP, Clark GR, Duncan EL, Brown MA. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genet. 2011 Mar;7(3):e1002027. doi: 10.1371/journal.pgen.1002027. Epub 2011 Mar 24. Citation on PubMed or Free article on PubMed Central
  • Horn D, Rupprecht E, Kunze J, Spranger J. Anauxetic dysplasia, a spondylometaepiphyseal dysplasia with extreme dwarfism. J Med Genet. 2001 Apr;38(4):262-5. Citation on PubMed or Free article on PubMed Central
  • Thiel CT, Horn D, Zabel B, Ekici AB, Salinas K, Gebhart E, Rüschendorf F, Sticht H, Spranger J, Müller D, Zweier C, Schmitt ME, Reis A, Rauch A. Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am J Hum Genet. 2005 Nov;77(5):795-806. Epub 2005 Sep 29. Citation on PubMed or Free article on PubMed Central
  • Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A. Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum. Am J Hum Genet. 2007 Sep;81(3):519-29. Epub 2007 Aug 6. Citation on PubMed or Free article on PubMed Central
  • Thiel CT, Rauch A. The molecular basis of the cartilage-hair hypoplasia-anauxetic dysplasia spectrum. Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):131-42. doi: 10.1016/j.beem.2010.08.004. Review. Citation on PubMed
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