Thanatophoric dysplasia

Thanatophoric dysplasia
Classification and external resources
ICD-10	Q77.1
OMIM	187600
DiseasesDB	29403
eMedicine	ped/2233
MeSH	D013796

Thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra skin on the arms and legs.

Symptoms

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]

Causes

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

Classification

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

The term thanatophoric is Greek for "death bearing". Children with this condition are usually stillborn or die shortly after birth from respiratory failure. The 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 brain seizures. The oldest current known TD survivor is a 23-year old male. Another male lived to age 20. Two children with TD aged 8 and 10, a male and a female, are known in Germany. There is also a 5-year old male living with TD who is able to spend several hours off ventilator support.

Incidence/Prevalence

This condition affects about 1 in 60,000 births.^[5]

References

1. ^ http://www.thefetus.net/page.php?id=383
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. ^ 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. http://edrv.endojournals.org/cgi/pmidlookup?view=long&pmid=10696568. 

External links

• GeneReview/NCBI/NIH/UW entry on Thanatophoric Dysplasia
• Thanatophoric dysplasia at NLM Genetics Home Reference