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CASE REPORT
Year : 2015  |  Volume : 42  |  Issue : 3  |  Page : 210-212

Thanatophoric dysplasia: Antenatal to postmortem


1 Department of Radiodiagnosis, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
3 Department of Pathology, Yenepoya Medical College, Mangalore, Karnataka, India

Date of Web Publication16-Sep-2015

Correspondence Address:
Dr. Chanabasappa V Chavadi
Flat No: C-1-13, K.M.C Staff Quarters, Light House Hill Road, Mangalore - 575 001, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-5009.165584

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  Abstract 

Thanatophoric dwarfism (TD), literally meaning death seeking dwarf, is the most common form of lethal bone dysplasia characterized by severe micromelia, extra folds of skin and narrow chest. Other signs include small ribs, underdeveloped lungs, cloverleaf skull, hypertelorism and protuberant abdomen. A short neck, depressed nasal bridge and hypoplastic mandible may also be present. Hydrocephalus is uncommon but is another poor prognostic sign. The diagnosis is usually made with the ultrasonography in the second trimester. Based on the morphological characters, this condition is sub-divided into type 1 and type 2. Fetuses with this condition are either still-born or die shortly after birth. Antenatal sonographic, postpartum radiological and autopsy findings of a case of type 1 TD with a relatively uncommon association of hydrocephalus is discussed.

Keywords: Autopsy, lethal, skeletal dysplasia, thanatophoric dysplasia, ultrasound


How to cite this article:
Chavadi CV, Mahale N, Jasthi G, Prabhu S, Kory S. Thanatophoric dysplasia: Antenatal to postmortem. J Sci Soc 2015;42:210-2

How to cite this URL:
Chavadi CV, Mahale N, Jasthi G, Prabhu S, Kory S. Thanatophoric dysplasia: Antenatal to postmortem. J Sci Soc [serial online] 2015 [cited 2019 Oct 14];42:210-2. Available from: http://www.jscisociety.com/text.asp?2015/42/3/210/165584


  Introduction Top


Thanatophoric dysplasia (TD) is a congenital, sporadic, lethal skeletal dysplasia characterized by severe shortening of the limbs, small conical thorax, platyspondyly, and macrocephaly. It is of two major subtypes viz. a short curved femur characterizes type 1, while a straighter femur with cloverleaf skull characterizes type 2.


  Case Report Top


A 24-year-old female, primigravida at 30 weeks of gestation was referred for routine antenatal ultrasonography that revealed a single live fetus in cephalic presentation with dilated right atrium and right ventricle [Figure 1]a, dilated pulmonary artery [Figure 1]b, narrow thorax and protuberant abdomen [Figure 1]c and f; dilated cerebral lateral ventricles [Figure 1]d. Abdominal circumference was corresponding to 29-30 weeks [Figure 1]e. The long bone of fetus were short with femur, humerus, tibia and ulna [Figure 2]a-d corresponding to 15-18 weeks (<2 nd centile) suggestive of severe micromelia. Also, radius and fibula were short with flattened vertebral bodies. Lethal dwarfism syndrome of TD was suggested, and the patient was advised termination of pregnancy.
Figure 1: (a) Axial chest with dilated right atrium (RA) and right ventricle (RV). (b) Three vessel view of upper chest with dilated pulmonary artery (PA), normal aorta (AO) and superior vena cava (SVC). (c and f) Sagittal (c) and coronal view (f) with narrow thorax and protuberant abdomen. (d) Axial section of the brain with dilated lateral ventricles. (e) Axial section of abdomen


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Figure 2: (a and b) Short femur and humerus with the appearance of "telephone receiver." (c and d) Short tibia and ulna respectively


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Postmortem infantogram (fetus radiograph) revealed narrow chest with short ribs [Figure 3]a and b. Severe flattening of vertebral bodies (platyspondyly) with increased intervertebral distance [Figure 3]c, short and small iliac bones with horizontal acetabular roofs and "telephone receiver femurs" [Figure 3]d suggestive of type 1 TD.
Figure 3: (a) Radiograph of the fetus (infantogram) anteroposterior view: Large skull, narrow thorax, short thick bowed tubular bones of extremities. (b) Lateral view: Severe flattening of vertebral bodies (platyspondyly), short ribs. (c) Lumbar spine lateral view: Increased intervertebral distance, (d) Short and small iliac bones with horizontal acetabular roofs, "telephone receiver femurs"


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Autopsy findings confirmed the diagnosis of TD with additional apparent findings of large head with frontal bossing [Figure 4]a, thickened soft tissues with redundancy of the skin of extremities [Figure 4]b, short hands [Figure 4]c, small lungs with relatively large cardia and large liver [Figure 4]d and e.
Figure 4: (a) Comparatively large head with frontal bossing, protuberant abdomen. (b) Thickened soft tissues with redundancy of the skin of extremities, (c) very short hands with sausage-like fingers. (d) Autopsy-small lungs with relatively large cardia. (e) Large liver


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  Discussion Top


Thanatophoric dysplasia is a lethal skeletal dysplasia, inherited in an autosomal dominant manner. It is the 2 nd most common lethal skeletal dysplasia after osteogenesis imperfecta type 2. [1] The common denominator for all lethal skeletal dysplasia is narrow thorax with pulmonary hypoplasia. Hydrocephalus detected in this case is a rare association and dictates poor prognosis. TD has an estimated incidence of 1 in 20,000-50,000 births and is an autosomal dominant condition. [2] Two types are observed. Type 1 TD is characterized by marked underdeveloped skeleton and short curved long bones. The pelvic bones and vertebral columns are underdeveloped, cloverleaf skull may or may not be present. [3] Whereas in type 2 TD, the long bones are not as short as in type 1 and not curved. The fetuses with type 2 TD are reported to have cloverleaf skull with premature closures of coronal and lambdoid sutures.

Molecular analysis of the fibroblast growth factor III receptor gene in both subtypes suggests that this is a genetically homogenous disorder. This usually leads to in-utero death of the fetus; the longest survival, however, has been reported to be of 9 years. [4]

Long bone measurement helps to determine which part of the limb are more severely shortened. The skeletal dysplasias may then be divided into following broad categories: Rhizomelic, mesomelic and micromelic types. Severe micromelia is seen with most of the lethal dysplasias represented most commonly by TD. Other features on antenatal sonography include comparatively large head with frontal bossing, protuberant abdomen and thickened soft tissues of extremities. [5]

Radiographic features include severe micromelia with bowing of extremities, skull has a large base and prominent frontal bone, narrow chest with short ribs, reduction of interpedicular spaces of last few lumbar vertebrae. [6] Small and square iliac wings, narrow sacrosciatic notch and horizontal acetabular roof. All these changes are similar to those seen in achondroplasia. The feature distinguishing TD from achondroplasia is severe vertebral plana and excessive intervertebral space. Short tubular bones are bowed; the metaphyseal areas are irregular and frequently cupped. [7]

Cerebral abnormalities reported in TD are dysplastic temporal cortex, fiber tract deformities, megalencephaly, and hydrocephalus. [8] Etiology of hydrocephalus may be dysmorphic choroid plexus. With early screening is gaining importance, ultrasound features described first trimester include dysmorphic indented choroid plexus with the abnormal contour of the calvarium and increased nuchal translucency, [9] limb shortening may also be apparent. Recently, cell-free fetal DNA analysis in maternal plasma is been added to the diagnostic tools for diagnosis of TD.


  Conclusion Top


Thanatophoric dwarfism is a lethal form of dwarfism, death resulting from respiratory failure or brain stem compression due to the narrow foramen magnum. Genetic analysis may play a role in early detection when suspected on sonography. Ultrasound plays a key role in diagnosis, postmortem radiographs and autopsy may provide more information for further research.


  Acknowledgment Top


Department of Pathology.

 
  References Top

1.
Dighe M, Fligner C, Cheng E, Warren B, Dubinsky T. Fetal skeletal dysplasia: An approach to diagnosis with illustrative cases. Radiographics 2008;28:1061-77.  Back to cited text no. 1
    
2.
Lam AC, Lam YY, Tong TM, Chan DK, Lau WL, Ng DK, et al. Thanatophoric dysplasia type 1 (TD1) without "telephone receivers". HK J Paediatr 2006;11:320-3.  Back to cited text no. 2
    
3.
Langer LO Jr, Yang SS, Hall JG, Sommer A, Kottamasu SR, Golabi M, et al. Thanatophoric dysplasia and cloverleaf skull. Am J Med Genet Suppl 1987;3:167-79.  Back to cited text no. 3
    
4.
Baker KM, Olson DS, Harding CO, Pauli RM. Long-term survival in typical thanatophoric dysplasia type 1. Am J Med Genet 1997;70:427-36.  Back to cited text no. 4
    
5.
Burrows PE, Stannard MW, Pearrow J, Sutterfield S, Baker ML. Early antenatal sonographic recognition of thanatophoric dysplasia with cloverleaf skull deformity. AJR Am J Roentgenol 1984;143:841-3.  Back to cited text no. 5
    
6.
Fink AM, Hingston T, Sampson A, Ng J, Palma-Dias R. Malformation of the fetal brain in thanatophoric dysplasia: US and MRI findings. Pediatr Radiol 2010;40 Suppl 1:S134-7.  Back to cited text no. 6
    
7.
Edeiken J, Rhodes PJ. Thanatophoric dysplasia. In: Roentgen Diagnosis of Diseases of Bone. 2 nd ed., Vol. 1. Baltimore: The Williams and Wilkins Company; 1973. p. 75-6.  Back to cited text no. 7
    
8.
Tavormina PL, Shiang R, Thompson LM, Zhu YZ, Wilkin DJ, Lachman RS, et al. Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. Nat Genet 1995;9:321-8.  Back to cited text no. 8
    
9.
Tonni G, Palmisano M, Ginocchi V, Ventura A, Baldi M, Baffico AM. Dysmorphic choroid plexuses and hydrocephalus associated with increased nuchal translucency: Early ultrasound markers of de novo thanatophoric dysplasia type II with cloverleaf skull (Kleeblattschaedel). Congenit Anom (Kyoto) 2014;54:228-32.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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Abstract
Introduction
Case Report
Discussion
Conclusion
Acknowledgment
References
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