Thanatophoric dysplasia or thanatophoric dwarfism is a uniformly lethal osteochondrodysplasia characterized by severe limb shortening (micromelia), bowing of limbs, narrow thorax and protuberant abdomen. (1)
Two subtypes of thanatophoric dysplasia are described: (2)
-Type I: characterized by shortness and bowing in the long bones. It may show cloverleaf skull, but it never reaches the strikingly trilobed configuration
-Type II may show cloverleaf skull and short, straight, long bones.The differential diagnosis between the two depends on the radiographic findings and histology.
Most cases have been sporadic. It has reported to be caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, but exactly how cytogenetic abnormalities might lead to TD is unclear. (3)
The diagnosis is usually suspected by antenatal ultrasound examination and confirmed by molecular analysis. Sonographic features suggestive of TD are macrocephaly, vertebral ossification defect, bowed femori, micromelia, and small thorax with protuberant abdomen. (1)Chitty and al (4), in a cohort of forty tow cases of TD, demonstrated that limb shortening in TD is sonographically apparent from as early as 13 weeks’ gestation, with minimal change in size after 20 weeks. Similarly, head circumference is increased throughout gestation, a feature that is present as early as the first trimester.Then, in the first trimester of the pregnancy, TD should be suspected if nuchal brightness and extremity shortness are noted in the ultrasonographic examination. (2)In high risk cases, samples for genetic investigation can be obtained by amniocentesis earliest at weeks 15-18 or by chorionic villus samples at weeks 10-12. (2) However, Chitty et al (4) had proposed analysis of cell-free fetal DNA on maternal plasma in three of forty tow pregnancies with TD. That confirmed the presence of mutation in the fibroblast growth factor receptor 3 (FGFR 3) gene. This method seems to be a safe and accurate prenatal confirmed diagnosis.Differential diagnosisThe differential diagnosis should include spondylo-epiphyseal dysplasia congenital but will also the short-ribbed polydactyly. (4)
Other features include polyhydramnios, large head, frontal bossing, cloverleaf skull, prominent eyes, hypertelorism, small pelvis and a depressed nasal bridge. It was observed that the abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester on ultrasound. (1,5)
The classical features on radiography include severe platyspondyly, short ribs, small ilia, markedly shortened limb bones with telephone receiver-like curved femora and curved clavicles resembling bicycle handle bars. (6)
Thanatophoric dysplasia is typically a neonatal lethal condition (3). However, Nikkel and al (7) had described history and skeletal findings in a 28 years old woman how affected by thanatophoric dwarfism. There is development of seizures, progression of craniocervical stenosis, ventilator dependence, limitations in motor and cognitive abilities, intermittent catheterization due to a neurogenic bladder, urinary tract infections and regular menstruation.Recurrence riskSince the TD usually occurs sporadically, the recurrence risk is low, with estimated rate of only 2%. However, there could have been a recurrence, with autosomal dominant mode of inheritance, which is less common. (6)
1. Naveen NS, Murlimanju BV, Kumar V, Pulakunta T, H J. Thanatophoric Dysplasia: A Rare Entity. Oman Med J. mai 2011;26(3):196.2. Gülaşı S, Atıcı A, Çelik Y. A Case of Thanatophoric Dysplasia Type
2: A Novel Mutation. J Clin Res Pediatr Endocrinol. mars 2015;7(1):73.
3. Turgut M, Demirhan O, Tunc E, Bucak IH, Canoz PY, Temiz F, et al. Diagnosis of chromosomal abnormalities in a patient with thanatophoric dysplasia (TD) type I: The first report describing an important association between cytogenetic findings and TD. Am J Case Rep. 2012;13:109.
4. Chitty LS, Khalil A, Barrett AN, Pajkrt E, Griffin DR, Cole TJ. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat Diagn. mai 2013;33(5):416.
5. Grangé G. Chapitre 22 - Maladies osseuses. In: Guide Pratique de L’échographie Obstétricale et Gynécologique (2e édition)
6. Davanageri RS, Shokeen PD, Bannur HB, Patil KP. Thanatophoric Dysplasia Type I: A Rare Case Report at Fetal Autopsy. J Lab Physicians. déc 2014;6(2):121.
7. Nikkel SM, Major N, King WJ. Growth and development in thanatophoric dysplasia – an update 25 years later. Clin Case Rep. déc 2013;1(2):75.