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.
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.
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.
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.
If the patient survives, 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 can 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 because of glaucoma.
Thanatophoric Dysplasia with Kleeblattschädel (Cloverleaf Skull with Thanatophoric Dwarfism; Thanatophoric Dysplasia type
II): Autosomal dominant, lethal micromelic dwarfism with cloverleaf head
and small facies; also caused by mutations in FGFR3.
Thanatophoric Dysplasia, Glasgow Variant (Neonatally
Lethal Short-Limb Skeletal Dysplasia, Glasgow type): Autosomal recessive
disorder that combines dwarfism with cataracts, anemia, and
Jarcho-Levin Syndrome: A rare
genetic disorder characterized by distinctive malformations including short
thorax because of fusion of thoracic vertebrae and ribs. This skeletal
problems often leads to respiratory insufficiency, pneumonia resulting in
life-threatening complications. Other features include vertebral dysplasia,
and hemivertebrae. In addition, abnormalities with the cervical vertebrae
may cause shortness of the neck, limited neck motion, and an abnormally low
hairline appearance. During the infancy period, the abdomen may be
abnormally prominent and the arms and legs may appear unusually long
suggesting often a marfanoid appearance. This disorder is thought to be
inherited as an autosomal recessive genetic trait.
Diastrophic Dysplasia: An autosomal recessive
inherited form of short-limb dwarfism associated with spine ...