Thanatophoric dysplasia is a severe

skeletal A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

disorder characterized by a disproportionately small

ribcage The rib cage, as an enclosure that comprises the ribs, vertebral column and sternum in the thorax of most vertebrates, protects vital organs such as the heart, lungs and great vessels. The sternum, together known as the thoracic cage, is a sem ...

, 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 The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the crea ...

, small

ribs The rib cage, as an enclosure that comprises the ribs, vertebral column and sternum in the thorax of most vertebrates, protects vital organs such as the heart, lungs and great vessels. The sternum, together known as the thoracic cage, is a semi- ...

, underdeveloped

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...

s, and an enlarged head with a large

forehead In human anatomy, the forehead is an area of the head bounded by three features, two of the skull and one of the scalp. The top of the forehead is marked by the hairline, the edge of the area where hair on the scalp grows. The bottom of the fo ...

and prominent, wide-spaced eyes. Thanatophoric dysplasia is a lethal skeletal

dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs ( macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopi ...

divided into two subtypes. Type I is characterized by extreme

rhizomelia Rhizomelia refers to either a disproportion of the length of the proximal limb, such as the shortened limbs of achondroplasia, or some other disorder of the hip or shoulder. According to Stedman's medical dictionary "rhizomelic" means "relating to ...

, bowed long bones, narrow

thorax The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the c ...

, a relatively large head, normal trunk length and absent cloverleaf skull. The spine shows

platyspondyly Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condit ...

, the cranium has a short base, and, frequently, the

foramen magnum The foramen magnum ( la, great hole) is a large, oval-shaped opening in the occipital bone of the skull. It is one of the several oval or circular openings (foramina) in the base of the skull. The spinal cord, an extension of the medulla oblon ...

is decreased in size. The forehead is prominent, and hypertelorism and a

saddle nose Saddle nose is a condition associated with nasal trauma, congenital syphilis, relapsing polychondritis, granulomatosis with polyangiitis, cocaine abuse, and leprosy, among other conditions. The most common cause is nasal trauma. It is characteri ...

may be present. Hands and feet are normal, but fingers are short. Type II is characterized by short, straight long bones and cloverleaf skull. It presents with typical telephone-handle shaped long bones and H-shaped vertebrae.

Causes

It can be associated with missense mutations in

fibroblast growth factor receptor-3 Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the ''FGFR3'' gene. FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location q16.3, is expressed i ...

. It is inherited in an autosomal dominant manner.

Diagnosis

Classification

Infants with type 1 thanatophoric dysplasia also have curved thigh bones, flattened bones of the

spine Spine or spinal may refer to: Science Biology * Vertebral column, also known as the backbone * Dendritic spine, a small membranous protrusion from a neuron's dendrite * Thorns, spines, and prickles, needle-like structures in plants * Spine (zoolo ...

(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.

Prognosis

The term thanatophoric is

Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...

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 Tracheotomy (, ), or tracheostomy, is a surgical airway management procedure which consists of making an incision (cut) on the anterior aspect (front) of the neck and opening a direct airway through an incision in the trachea (windpipe). The r ...

. There may also be evidence of

spinal stenosis Spinal stenosis is an abnormal narrowing of the spinal canal or neural foramen that results in pressure on the spinal cord or nerve roots. Symptoms may include pain, numbness, or weakness in the arms or legs. Symptoms are typically gradual i ...

and seizures. The oldest known living TD survivor as of 2013 was a 29-year-old woman. 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. As of 2021 Christopher Álvarez, 24, is a Colombian living with TD in New York City.

Incidence

This condition affects about 1 in 60,000 births.

References

External links

GeneReview/NCBI/NIH/UW entry on Thanatophoric Dysplasia
* {{Receptor deficiencies Cell surface receptor deficiencies Rare diseases Thanatos