Metaphyseal Dysplasia without Hypotrichosis

Cartilage-hair hypoplasia (CHH) is a pleiotropic disorder characterized by short-limbed dwarfism, coneshaped epiphyses, metaphyseal flaring and irregularities, sparse and light colored hair of abnormally small caliber, immunological defects manifested by unusual susceptibility to chickenpox, and other hematological anomalies such as neutropenia and anemia. Some patients may also have Hirschsprung disease, impaired spermatogenesis, and increased susceptibility to cancer. Skeletal abnormalities may include incomplete extension at the elbows, chest deformities, lumbar lordosis, joint laxity, bowed legs, genu varum, and excessively long fibula distally relative to the tibia, in addition to dwarfism. Hypoplasia of the cartilage is seen microscopically. Metaphyseal dysplasia without hypotrichosis was initially described as a distinct entity from CHH with identical skeletal features, and lacking hypotrichosis and immunodeficiency. Anauxetic dysplasia is a form of extreme short stature of prenatal onset, hypodontia, and mild mental retardation. Recent data shows that these three disorders are allelic as each condition is caused by mutations in the RNase MRP (RMRP) gene. The RMRP gene encodes the RNA subunit of a RNA processing enzyme complex (endoribonuclease).

Tests Available

Forms and Documents

Test Details

RMRP
  • Confirmation of a clinical diagnosis
  • Differentiation between CHH and other causes of dwarfism
  • Identification of patients at increased risk of infections or cancer
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

225
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 404.2 Abnormalities of the hair
  • 757 Congenital anomalies of the integument; Includes: anomalies of skin, subcutaneous tissue, hair, nails, and breast
  • 259.4 Dwarfism, not elsewhere classified Dwarfism: NOS constitutional
  • 783.4 Lack of expected normal physiological development in childhood
  • 733 Other disorders of bone and cartilage
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References

  1. Ridanpaa M, et al., Mutations in the RNA Component of RNase MRP Cause a Pleiotropic Human Disease, Cartilage-Hair Hypoplasia Cell 104:195-203 (2001)
  2. Bonafe L, et al., RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of singlenucleotide polymorphisms Clin Genet 61:146-151 (2002)
  3. Ridanpaa, M, et al., Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin of the major 70A?G mutation of the untranslated RMRP Eur J of Hum Genet 10:439-447 (2002)