Thanatophoric Dysplasia

[sff_corgi_lj]

Background: Thanatophoric dysplasia (TD) is the most common form of skeletal dysplasia that is lethal in the neonatal period (the term thanatophoric derives from the Greek, meaning death bringing). Characteristics of TD include severe shortening of the limbs, a narrow thorax, macrocephaly, and a normal trunk length. TD is divided into 2 clinically defined subtypes. TD type 1 (TD1), the most common subtype, features a normally shaped skull and curved long bones (shaped like a telephone receiver) with the femurs affected most. TD type 2 (TD2) features a cloverleaf-shaped skull and straight femurs. Some clinical overlap exists between the 2 subtypes. Autosomal dominant mutations in the fibroblast growth factor receptor 3 gene (FGFR3), which has been mapped to chromosome band 4p16.3, results in both subtypes. The vast majority of cases are due to de novo mutations. Gonadal mosaicism has not been documented definitively.

Pathophysiology: The FGFR3 gene is a member of the tyrosine kinase receptor family. Ligand binding induces receptor homodimerization, as well as heterodimerization, that results in activation of tyrosine kinase function and potentiates many effects on cell growth and differentiation. Some authors suggest that mutations in FGFR3 lead to the formation of cysteine residues that create disulfide bonds between the extracellular domains of mutant monomers. Activation of the homodimer receptor complex increases its stability and promotes translocation of the complex into the nucleus, where it may interfere with terminal chondrocyte differentiation.

Frequency:

• In the US: TD has an incidence of 1 case per 10,000-35,000 live births.
• Internationally: Frequency in Spain is 2.7 cases per 100,000.

Mortality/Morbidity: Although the literature documents several reports of survival into childhood, TD virtually is always lethal in the neonatal period. Respiratory insufficiency secondary to reduced thoracic capacity or compression of the brainstem leads to death.

Sex: Males and females are affected equally.

Age: TD is lethal in neonates; however, long-term survival has been reported

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Medical Care: Inpatient care is necessary. Intubation may be performed as aggressive treatment for respiratory distress.

If aggressive treatment is deferred, palliative treatment consists of keeping the infant warm, comfortable, and nourished.

Further Inpatient Care:

• Admit patients to the neonatal intensive care unit if extended survival appears to be possible.

Further Outpatient Care:

• Outpatient care is indicated only in cases of long-term survival.

Transfer:

• Transfer to a long-term care facility or hospice may be required in infants in whom survival is prolonged.

Complications:

• Severe growth and developmental delay
• Hydronephrosis
• Hydrocephalus
• Ventilator dependency

Prognosis:

• TD usually is lethal in the first few days of life. Death is caused by respiratory insufficiency.

Patient Education:

• If a fetus is affected by TD and if the pregnancy has proceeded past the period during which a therapeutic abortion can take place, discuss aggressive and nonaggressive management frankly with the parents.

So... it wasn't likely, but it was possible that Sun Hudson could have survived functionally.