Thanatophoric dysplasia

Thanatophoric dysplasia
Radiogram of a baby born with thanatophoric dwarfism
Specialty	Medical genetics

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 and signs[]

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-handle shaped long bones and H-shaped vertebrae.^{[citation needed]}

Causes[]

It can be associated with missense mutations in fibroblast growth factor receptor-3. It is inherited in an autosomal dominant manner.^[2][3]

Diagnosis[]

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.^{[citation needed]}

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. A small number 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 as of 2013 was a 29-year-old woman.^[5] One man lived to be 26 years old. Another man lived to age 20. It was reported in 1998 that a 21 year old man with the condition lives in the United States, while two children with TD aged 10 and 12, a boy and a girl, were known in Germany. There was also a 6-year-old boy living with TD and two 1-year old boys.^[6] As of 2020 Christopher Álvarez, 23, is a Colombian living with TD in New York City.^[7]

Incidence[]

This condition affects about 1 in 60,000 births.^{[8][failed verification]}

References[]

External links[]

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