Cartilage–hair hypoplasia

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Cartilage-hair hypoplasia
Other names: McKusick type metaphyseal chondrodysplasia[1]: 578 
Cartilage-hair hypoplasia has an autosomal recessive pattern of inheritance
SymptomsShort limb dwarfism
Very fine thin light hairs and eyebrows
Hyperextensible joints of hand and feet
Abnormalities of spine
Defective antibody and cell mediated immunity

Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported by Victor McKusick in 1965.

Signs and symptoms

Bowing of right femur and tibia in individual with cartilage hair hypoplasia
  • Short limb dwarfism
  • Very fine, light hairs and eyebrows
  • Hyperextensible joints of hand and feet
  • Abnormalities of spine
  • Neutropenia
  • Defective antibody and cell mediated immunity



CHH is an autosomal recessive[2] inherited disorder. It is a highly pleiotropic disorder. A rarely encountered genetic phenomenon, known as uniparental disomy (a genetic circumstance where a child inherits two copies of a chromosome from one parent, as opposed to one copy from each parent) has also been observed with the disorder.[2]

An association between mutations near or within the ncRNA component of RNase MRP, RMRP, has been identified.[3][4][5][6] The endoribonuclease RNase MRP is a complex of RNA molecule and several proteins and it participates in cleavage of mitochondrial primers responsible for DNA replication and in pre-rRNA processing in the nucleolus.[7][8] The locus of the gene has been mapped to the short arm of chromosome 9.[9]


Patients with CHH usually suffer from cellular immunodeficiency. In the study of 108 Finnish patients with CHH, there was detected mild to moderate form of lymphopenia, decreased delayed type of hypersensitivity and impaired responses to phytohemagglutinin.[10] This leads to susceptibility to and, in some more severe cases, mortality from infections early in childhood. There has also been detected combined immunodeficiency in some patients.[11] Patients with CHH often have increased predispositions to malignancies.[11]


The diagnosis of this condition is ascertained via direct sequencing of the RMRP gene. The DDx includes other forms of short-limb dwarfism.[12]


A verified treatment for this disease is yet to be discovered.[citation needed]

See also


  1. James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology(10th ed.). Saunders. ISBN 0-7216-2921-0.
  2. 2.0 2.1 Sulisalo T, Makitie O, Sistonen P, Ridanpaa M, el Rifai W, Ruuskanen O, de la Chapelle A, Kaitila L (1997). "Uniparental disomy in cartilage-hair hypoplasia". European Journal of Human Genetics. 5 (1): 35–42. doi:10.1159/000484729. PMID 9156319.
  3. Bonafé L, Schmitt K, Eich G, Giedion A, Superti-Furga A (February 2002). "RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of single-nucleotide polymorphisms". Clinical Genetics. 61 (2): 146–51. doi:10.1034/j.1399-0004.2002.610210.x. PMID 11940090. S2CID 7284120.
  4. Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, Mäkitie O, Kaitila I, de la Chapelle A (2001). "Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia". Cell. 104 (2): 195–203. doi:10.1016/S0092-8674(01)00205-7. PMID 11207361. S2CID 13977736.
  5. Martin AN, Li Y (2007). "RNase MRP RNA and human genetic diseases". Cell Research. 17 (3): 219–26. doi:10.1038/ PMID 17189938.
  6. Kavadas FD, Giliani S, Gu Y, Mazzolari E, Bates A, Pegoiani E, Roifman CM, Notarangelo LD (2008). "Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations". The Journal of Allergy and Clinical Immunology. 122 (6): 1178–84. doi:10.1016/j.jaci.2008.07.036. PMID 18804272.
  7. Hsieh, C. L.; Donlon, T. A.; Darras, B. T.; Chang, D. D.; Topper, J. N.; Clayton, D. A.; Francke, U (1990). "The gene for the RNA component of the mitochondrial RNA-processing endoribonuclease is located on human chromosome 9p and on mouse chromosome 4". Genomics. 6 (3): 540–544. doi:10.1016/0888-7543(90)90483-b. PMID 2328993.
  8. Topper, J. N.; Clayton, D. A. (1990). "Characterization of human MRP/Th RNA and its nuclear gene: Full length MRP/Th RNA is an active endoribonuclease when assembled as an RNP". Nucleic Acids Research. 18 (4): 793–799. doi:10.1093/nar/18.4.793. PMC 330329. PMID 1690392.
  9. Sulisalo, T; Sistonen, P; Hästbacka, J; Wadelius, C; Mäkitie, O; de la Chapelle, A; Kaitila, I (1993). "Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis". Nature Genetics. 3 (4): 338–341. doi:10.1038/ng0493-338. PMID 7981754. S2CID 7752268.
  10. Mäkitie, O; Kaitila, I (1993). "Cartilage-hair hypoplasia--clinical manifestations in 108 Finnish patients". European Journal of Pediatrics. 152 (3): 211–7. doi:10.1007/bf01956147. PMID 8444246. S2CID 10611620.
  11. 11.0 11.1 Saulsbury, F. T.; Winkelstein, J. A.; Davis, L. E.; Hsu, S. H.; d'Souza, B. J.; Gutcher, G. R.; Butler, I. J. (1975). "Combined immunodeficiency and vaccine-related poliomyelitis in a child with cartilage-hair hypoplasia". The Journal of Pediatrics. 86 (6): 868–72. doi:10.1016/s0022-3476(75)80216-2. PMID 165279.
  12. "Orphanet: Cartilage hair hypoplasia". Archived from the original on 17 January 2021. Retrieved 25 February 2022.

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