Thanatophoric dysplasia

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

Thanatophoric dysplasia 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 brain seizures. The oldest known living TD survivor is a 25-year old male. Another male lived to age 20. 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.[5]

Incidence/Prevalence[edit]

This condition affects about 1 in 60,000 births.[6]

Radiological features[edit]

SKULL

  • ‘Cloverleaf skull’: this is due to lateral temporal bulging

CHEST

  • Small thorax
  • Short ribs with wide costochondral junctions
  • Small scapulae

VERTEBRAE

  • severe platyspondyly (Decreased Height of Vertebral Body)

PELVIS

  • horizontal acetabular roofs with medial spikes
  • small sacroiliac notches

LIMBS

  • marked shortness and bowing of the long bones. ‘Telephone handle’ appearance of the long bones: this is due to metaphyseal flaring
  • irregular metaphyses
  • short broad tubular bones in the hands and feet


US OBSTETRIC

  • Polyhydramnios, 75%
  • Nonimmune hydrops

References[edit]

  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. ^ 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. 
  6. ^ 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. 

External links[edit]