TD1; TDI; Dwarf, Thanatophoric; Thanatophoric Dwarfism; Thanatophoric Short Stature; TD type 1; TD type I

Thanatophoric Dysplasia, Type 1 (TD1) is a severe skeletal disorder characterized by a normal-shaped skull, curved thigh bones and flattened bones of the spine (platyspondyly). The term thanatophoric is Greek for “death bearing”. Infants with TD1 are usually stillborn or die shortly after birth from respiratory failure; however, a few affected individuals have survived into childhood with extensive medical help. This disorder is caused by mutations in the FGFR3 gene. The gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Mutations in this gene cause the FGFR3 protein to be overly active, which leads to the severe disturbances in bone growth. This condition occurs in 1 in 20,000 to 50,000 newborns.

Diagnostic testing:

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  Clinical examination;

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  Prenatal ultrasound with findings of growth deficiency, ventriculomegaly, macrocephaly, well-ossified skull and spine, platyspondyly of the vertebrae, micromelia, bowed femurs, narrow chest cavity with shortened ribs and polyhydramnios; and

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  Molecular genetic testing of the gene FGFR3.

Physical findings:

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  Growth deficiency of limbs of less than 5%;

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  Bowed femurs;

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  Shortened ribs;

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  Platyspondyly of the vertebrae;

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  Macrocephaly;

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  Large anterior fontanel;

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  Frontal bossing;

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  Proptosis; and

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  Low nasal bridge.

ICD-9: 756.4

Newborns with TD1 are stillborn or die shortly after birth. Very rare reports of survival into early childhood have been cited. Long-term survivors need neurologic, orthopedic, and audiologic evaluations, CT to monitor for craniocervical constriction, and EEG to monitor for seizure activity.

Treatment measures of the few survivors may include: antiepileptic drugs to control seizures, shunt placement for hydrocephaly, suboccipital decompression for relief of craniocervical junction constriction, and hearing aids.

SUGGESTED PROGRAMMATIC ASSESSMENT*

Suggested MER for Evaluation:

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  Clinical examination that describes diagnostic features of the impairment;

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  Audiologic evaluation;

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  Genetic testing; and

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  Imaging studies.

Suggested Listings for Evaluation:

REMARKS