Thanatophoric dysplasia
| Classification according to ICD-10 | |
|---|---|
| Q77.1 | Thanatophoric dysplasia |
| ICD-10 online (WHO version 2019) | |
The thanatophoric dysplasia ( TD , Platyspondylitische dysplasia type San Diego ) ( Greek thanatophor , lethal '; dysplasia . Greek dys ' bad 'and plassein form, shapes') is a fatal form of a severe growth and developmental disorder of the cartilage - bone tissue - osteochondrodysplasia (Greek osteo `` related to the bone '' and chondro `` related to the cartilage '') - which is a rare disease with a prevalence of around 1: 20,000 to 1: 50,000 in both sexes . A distinction is made between type I and type II, with type I being more common than type II.
A distinction must be made between platyspondylitic dysplasia type Torrance .
root cause
In children with a form of thanatophoric dysplasia, due to a rare genetic defect with mutations in the FGFR3 area ( receptor 3 of the fibroblast growth factor ) on chromosome 4 p16.3, which follows an autosomal dominant inheritance , there is a disorder of bone growth . The cartilage cells receive growth-inhibiting signals, which leads to skeletal malformations in the unborn child during pregnancy due to a disruption of the formation of bone tissue . Various physical abnormalities occur (see symptoms).
Symptoms
The child's physique is generally smaller than usual, the head appears relatively large (pseudo- macrocephaly ) and occasionally (in type I) or mostly (in type II) a differently pronounced clover-leaf shape. The forehead is bulging, the bridge of the nose sunk in, the chest (thorax) is narrow and narrow, the ribs short. The long tubular bones are bent and shortened, which leads to micromelia (see also short stature ). In type II, the femur does not have a bend. The hands are also comparatively short ( brachydactyly ). Cerebral malformations can be found in different forms.
diagnosis
In children with thanatophoric dysplasia, the above-mentioned specific growth disorders are noticeable during pregnancy, possibly also a trefoil skull and pronounced neck transparency . Frequently there is a Polyhydramnios and pregnant women fall decreased fetal movement on. A suspected diagnosis is possible prenatally by ultrasound . After amniocentesis , a molecular genetic examination of the cells of the unborn child can be used to search for mutations in the FGFR3 gene on chromosome 4. In type I, they concern the extracellular immunoglobulin- like domains of the transmembrane receptor protein that bind or regulate a fibroblast growth factor; in type II, the intracellular tyrosine kinase domain, which triggers signals and mediates cellular effects.
Therapy, prognosis
A cure is not yet possible. With a few exceptions, children with TD die in the perinatal period or in the neonatal period . Long-term survivors (4.75 and 3.7 years old; over 9 years old) have been reported. Due to the narrow and narrow chest, your lungs cannot develop and unfold before birth, so that after birth, respiratory insufficiency occurs due to the considerably restricted ventilation of the lungs. Damage to the respiratory center when the brainstem is compressed due to the small diameter of the occipital orifice can be an additional or sole cause of the failure of breathing.
literature
- Sarah Williams: The Flight of the Lark. The story of a short life. 2006, ISBN 3-7655-3905-8 .
Web links
Individual evidence
- ↑ Langer Lo, Yang Ss, Hall Jg, Sommer A, Kottamasu Sr: Thanatophoric Dysplasia and Cloverleaf Skull. 1987, accessed February 9, 2020 .
- ^ IM MacDonald, AG Hunter, PM MacLeod, SB MacMurray: Growth and development in thanatophoric dysplasia. In: Am J Med Genet. 33, 1989, pp. 508-512, PMID 2596513
- ↑ KM Baker, DS Olson, CO Harding, RM Pauli: Long-term survival in typical thanatophoric dysplasia type 1 . In: Am J Med Genet. tape 70 , no. 4 , 1997, p. 427-436 , PMID 9182787 .
- ↑ B. Karczeski, GR Cutting: Thanatophoric dysplasia . In: Gene Reviews. Last updated: September 30, 2008.
