thanatophoric dysplasia

Thanatophoric dysplasia is a lethal skeletal dysplasia. It is the most common lethal skeletal dysplasia followed by osteogenesis imperfecta type II.

Epidemiology

The estimated incidence is around 1:25,000-50,000 .

Pathology

Genetics

It results from a mutation coding for the fibroblast growth receptor 3 (FGFR3) located on chromosome 4p16.3. The type of receptor mutation is different from the FGFR mutation in achondroplasia. Inheritance is thought to be sporadic.

Subtypes

There are two recognized subtypes:

• type I: marked underdevelopment of skeleton, telephone handle femurs more pronounced
• type II
  • the presence of a cloverleaf skull may be a distinctive feature
  • limb shortening milder and bowing is not a feature

Associations

• polyhydramnios

Radiographic features

Antenatal ultrasound

It may be difficult to accurately diagnose before the 3 trimester (≈22 weeks) . Before that time it can be included in the differential if there is a short femur length measurement.

Sonographically-detectable features may include:

• relatively narrow thoracic cavity
• short, thick, bowed tubular bones, especially lower extremity
• thickened soft tissues of extremities
• comparatively large head with frontal bossing 
• a cloverleaf skull appearance may also be seen: type II (see case 3)

Plain radiograph 

Plain films are usually done postmortem, if done at all. Features include:

Limbs

• proximal portions of the long limbs are small, giving a rhizomelic appearance
• long bones (typically humeri and femora) have a typical "telephone handle" bowing with metaphyseal flaring

Iliac bones

• usually hypoplastic 
• small squared iliac wings
• may show trident acetabula

Chest

• narrow chest
• short horizontal ribs
• small scapulae

Skull and face

• relative macrocephaly 
• frontal bossing
• proptosis
• nasal bridge flattening 
• kleeblattschaedel (cloverleaf) skull (with type II)  

Spine

• platyspondyly: flattening of vertebral bodies
• normal trunk length

Treatment and prognosis

The condition is uniformly fatal within a few hours of birth either from respiratory failure or from brainstem compression from a narrow foramen magnum.

History and etymology

The term thanatophoric derives from the Greek words "thanatos" (θάνατος) meaning "death"  and "phoros" meaning "bearing/carrying/bringing".

See also

• skeletal dysplasias

Siehe auch:

• Osteogenesis imperfecta
• Platyspondylie
• Rhizomelie
• Achondroplasie
• Skelettdysplasie
• Polyhydramnion
• Makrozephalie
• Kleeblattschädel
• frontal bossing
• Schädel
• lethal skeletal dysplasias
• cloverleaf
• narrow thoracic cavity

und weiter:

• Aseptische Wirbelkörpernekrose
• Vertebra plana
• lemon sign
• asphyxierende Thoraxdysplasie (Jeune-Syndrom)
• congenital syndromes associated with enlarged ventricles
• narrow fetal thorax
• paediatric curriculum
• Mikromelie
• fetal limb bowing
• fibroblast growth factor receptor gene mutations
• Platyspondylitische Dysplasie Typ Torrance
• verminderter interpediculärer Abstand