Thanatophoric dysplasia

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Thanatophoric dysplasia
Thanatophoric-dwarf-102.jpg
Radiogram of a baby born with thanatophoric dwarfism
Classification and external resources
Specialty medical genetics
ICD-10 Q77.1
OMIM 187600
DiseasesDB 29403
eMedicine ped/2233
MeSH D013796

Thanatophoric dysplasia (thanatophoric dwarfism) is a severe skeletal disorder characterized by a disproportionately small ribcage, extremely short limbs and folds of extra skin on the arms and legs.

Symptoms[edit]

Infants with this condition have disproportionately short arms and legs with extra folds of skin. Other signs of the disorder include a narrow chest, small ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Thanatophoric dysplasia is a lethal skeletal dysplasia divided into two subtypes. Type I is characterized by extreme rhizomelia, bowed long bones, narrow thorax, a relatively large head, normal trunk length and absent cloverleaf skull. The spine shows platyspondyly, the cranium has a short base, and, frequently, the foramen magnum is decreased in size. The forehead is prominent, and hypertelorism and a saddle nose may be present. Hands and feet are normal, but fingers are short. Type II is characterized by short, straight long bones and cloverleaf skull.[1] It presents with typical telephone handled shaped long bones and a H-shaped vertebrae.

Causes[edit]

It can be associated with missense mutations in fibroblast growth factor receptor-3.[2][3]

Classification[edit]

Infants with type 1 thanatophoric dysplasia also have curved thigh bones, flattened bones of the spine (platyspondyly) and shortened thoracic ribs. Note: Prenatal ultra-sound images of the ribs sometimes appear asymmetrical when in fact they are not. In certain cases, this has caused a misdiagnosis of Osteogenisis Imperfecta (OI) type II.

An unusual head shape called kleeblattschädel ("cloverleaf skull") can be seen with type 2 thanatophoric dysplasia.[4]

Prognosis[edit]

The term thanatophoric is Greek for "death bearing". Children with this condition are usually stillborn or die shortly after birth from respiratory failure, however a small number of individuals have survived into childhood and a very few beyond. Survivors have difficulty breathing on their own and require respiratory support such as high flow oxygen through a canula or ventilator support via tracheostomy. There may also be evidence of spinal stenosis and seizures. The oldest known living TD survivor is a 29-year-old female.[5] One male lived to be 26 years old. Another male lived to age 20. TD survivor, Chrisopher Álvarez, 18, is Colombian living in New York. Two children with TD aged 10 and 12, a male and a female, are known in Germany. There is also a 6-year-old male living with TD and two 1-year old males.[6]

Incidence and prevalence[edit]

This condition affects about 1 in 60,000 births.[7]

References[edit]

  1. ^ Norris, Cheryl D., George Tiller, Philippe Jeanty, Srini Malini (2008-12-12). "Thanatophoric dysplasia in monozygotic twins". TheFetus.net. Archived from the original on December 12, 2008. Retrieved 2016-03-01. 
  2. ^ Bonaventure J, Gibbs L, Horne WC, Baron R (2007). "The localization of FGFR3 mutations causing thanatophoric dysplasia type I differentially affects phosphorylation, processing and ubiquitylation of the receptor". FEBS J. 274 (12): 3078–93. doi:10.1111/j.1742-4658.2007.05835.x. PMID 17509076. 
  3. ^ Lievens PM, Liboi E (2003). "The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum". J. Biol. Chem. 278 (19): 17344–9. doi:10.1074/jbc.M212710200. PMID 12624096. 
  4. ^ Norman AM, Rimmer S, Landy S, Donnai D (1992). "Thanatophoric dysplasia of the straight-bone type (type 2)". Clin. Dysmorphol. 1 (2): 115–20. doi:10.1097/00019605-199204000-00008. PMID 1345514. 
  5. ^ Nikkel, Sarah M.; Major, Nathalie; King, W. James (2013-12-01). "Growth and development in thanatophoric dysplasia – an update 25 years later". Clinical Case Reports 1 (2): 75–78. doi:10.1002/ccr3.29. ISSN 2050-0904. PMC 4184754. PMID 25356217. 
  6. ^ Baker, K. M.; Olson, D. S.; Harding, C. O.; Pauli, R. M. (1997). "Long-term survival in typical thanatophoric dysplasia type 1". American Journal of Medical Genetics 70 (4): 427–436. doi:10.1002/(SICI)1096-8628(19970627)70:4<427::AID-AJMG18>3.0.CO;2-J. PMID 9182787. 
  7. ^ Vajo, Zoltan; Francomano CA; Wilkin DJ (2000). "The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans". Endocr. Rev. 21 (1): 23–39. doi:10.1210/er.21.1.23. PMID 10696568. 

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