A severe form of micromelic dwarfism with narrow thorax with short ribs, severe hydrocephalus, and hydronephrosis. Death generally occurs in the first hours of life.
French pediatrician Maroteaux used the term “thanatophoric—death bearing” in 1967 to describe that patients die shortly after birth.
1:10,000 to 1:35,000 live births.
Autosomal dominant inheritance, but most cases are de novo mutations.
Caused by mutation in the fibroblast growth factor receptor-3 gene (FGFR3, which belongs to the tyrosine kinase receptors) located on 4p13.6. Formation of cysteine residues with disulfide bonds between the extracellular domains of mutant monomers has been reported as resulting from FGFR3 mutation. Perturbation of terminal chondrocyte differentiation could be the final result of this mutation.
Clinically evocated in a baby with severe shortening of the limbs, narrow thorax, macrocephaly, and normal trunk length. Antenatal diagnosis on ultrasonographic findings is possible. Thanatophoric Dwarfism can be classified into two subgroups according to the morphologic findings, with prominent curved femur suggesting ☞Type I Thanatophoric Dwarfism (TD 1) and with marked clover-leaf skull and relatively straight long bones, favoring ☞Type II Thanatophoric Dwarfism (TD 2).
Major skeletal deformations observed involve: skull (macrocephaly, frontal bossing, depressed nasal bridge), limbs (micromelic dwarfism, brachydactyly, enlarged and bowed diaphysis), and trunk (abnormal rib with narrow rib cage, scapula anomaly, intervertebral disk anomaly, abnormal vertebral size, and pelvis anomaly). Other clinical features can include glaucoma, temporal lobe heterotopias, hydrocephalus, profound mental retardation, and hypotonia in survivors. Respiratory insufficiency is frequent because of restrictive thoracic deformations.
Precautions before anesthesia
Because of the early death, it will be extremely rare for an anesthesiologist to provide care for surgery, except for airway and cardiovascular support at birth. Only one case report is described with the child undergoing suboccipital decompression at 3 months. A complete evaluation of neurological function (clinical, EEG, CT) must be obtained. Evaluate respiratory function (clinical, chest radiographs, pulmonary function test, arterial blood gas analysis).
Careful intraoperative positioning is needed. Both arterial and venous access may be difficult because of limb deformations. Regional anesthesia is not contraindicated but can be difficult to perform. Postoperative physiotherapy is useful. Postoperative mechanical ventilatory support may be necessary.
Avoid atropine and other cholinergic drugs if glaucoma present.
Other conditions to be considered
☞Thanatophoric Dysplasia, Glasgow Variant (Neonatally Lethal Short-Limb Skeletal Dysplasia, Glasgow Type): Autosomal recessive disorder that combines dwarfism with cataracts, anemia, and hepatosplenomegaly.
☞Jarcho-Levin Syndrome: Rare autosomal ...