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CASE REPORT
Year : 2013  |  Volume : 2  |  Issue : 4  |  Page : 275-277

Case report of Thanatophoric dysplasia: A lethal skeletal dysplasia


Department of Pathology, Katuri Medical College, Guntur, Andhra Pradesh, India

Date of Web Publication26-Nov-2013

Correspondence Address:
Neelima Tirumalasetti
c/o Ch.Venkat Rao, Door No: 5-54-80, 6/18, Brodipet, Guntur - 522 002, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2277-8632.122168

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  Abstract 

Skeletal dysplasias constitute a heterogeneous group of bone growth disorders resulting in abnormal shape and size of the skeleton. Thanatophoric dysplasia (TD) is one of the rare, lethal osteochondrodysplasia. A 28-year-old, healthy, non-consanguineously married woman with history of one previous abortion was brought to the hospital at 26 weeks of gestation for antenatal evaluation. Ultrasound examination showed a single live fetus with biparietal diameter corresponding to 26 weeks of gestation. Femur, humerus, and other long bones were very short with femoral length corresponding to 16-18 weeks. The thoracic cavity was small and irregular. Based on these findings, a diagnosis of lethal bony dysplasia was offered. Medical termination of pregnancy was performed at 28 weeks of gestation. Post mortem autopsy and radiological examination confirmed the diagnosis. This case report emphasizes the need into the insight regarding the problem of congenital malformations and their early prenatal diagnosis, which will aid in an alternative option of termination of pregnancy when an affected fetus is detected. Genetic counseling and evaluation of the prognosis on the basis of molecular results should be considered an important issue.

Keywords: Dwarfism, dwarf, fibroblast growth factor receptor 3, prenatal, Thanatophoric dysplasia


How to cite this article:
Tirumalasetti N. Case report of Thanatophoric dysplasia: A lethal skeletal dysplasia. J NTR Univ Health Sci 2013;2:275-7

How to cite this URL:
Tirumalasetti N. Case report of Thanatophoric dysplasia: A lethal skeletal dysplasia. J NTR Univ Health Sci [serial online] 2013 [cited 2020 Jul 15];2:275-7. Available from: http://www.jdrntruhs.org/text.asp?2013/2/4/275/122168


  Introduction Top


Skeletal dysplasias constitute a heterogeneous group of bone growth disorders resulting in abnormal shape and size of the skeleton. [1] Thanatophoric dysplasia (TD) is one of the rare, lethal osteochondrodysplasia. [2] The term 'thanatophoric' derives from the Greek word "thanatophorus" which means "death bringing". [1] This term was first described and used by Maroteux for dwarf babies who died in first hour of life. [3] Characteristics of TD include severe shortening of the limbs, a narrow thorax with protuberant abdomen, macrocephaly, and a normal trunk length. [1],[3]

We report a case of TD diagnosed antenatally on a routine prenatal ultrasound scanning.


  Case Report Top


A 28-year-old, healthy, non-consanguineously married woman with history of one previous abortion was brought to the hospital at 26 weeks of gestation for antenatal evaluation. The pregnancy was reported uneventful. Ultrasound examination showed a single live fetus, and amniotic fluid was adequate. Biparietal diameter of the fetus was corresponding to 26 weeks of gestation. Femur, humerus, and other long bones were very short with femoral length corresponding to 16-18 weeks. The thoracic cavity was small and irregular. Based on these findings, a diagnosis of a lethal bony dysplasia was offered. A second ultrasound scan performed 2 weeks later confirmed the previous findings and a diagnosis of thanatophoric dwarf was made. The parents were counseled for termination of pregnancy and a medical termination of pregnancy was performed at 28 weeks of gestation.

On examination, the fetus was weighing 780 grams and was small in length. Autopsy showed macrocephaly, frontal bossing, and mid-face hypoplasia with depressed nasal bridge, low-set ears, a large mouth, and a bell-shaped chest. Both the upper and lower limbs were grossly shortened and bowed. Brachydactyly was present [Figure 1].
Figure 1: Thanatophoric dysplasia: Showing tetramicromelia with bowing. Fetus shows large head, frontal bossing with mid-face hypoplasia, depressed nasal bridge, low set ears, large mouth, and narrow thoracic cage

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The post abortion radiograph showed short humerii, femorii, forearm bones, and tibiae with metaphyseal flaring. The head was large and clover leaf shaped. The thoracic cage was narrow. The vertebrae showed H-shaped platyspondyly. The ribs were short. There was reduced height of iliac bones with increased horizontal width. The acetabulae were flat [Figure 2].
Figure 2: Radiograph showing short humerii, femorii, forearm bones, and tibiae with metaphyseal fl aring. The head is large and clover leaf shaped. The thoracic cage is narrow with short ribs. The vertebrae show H shaped platyspondyly

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  Discussion Top


TD has a reported incidence between 1/6,000 and 1/17,000 births. Both sexes are equally affected. There is no particular ethnic or racial predisposition and recurrence risk is sporadic. [4]

TD is characterized by an abnormal head, face, thorax, and skeleton. The head anomaly consists of megacephaly, occasionally with a cloverleaf-shaped skull known as kleeblattschödel. In the face, excess skin usually yields a "boxers' face" appearance, with frontal bossing and a depressed nasal bridge. A hypoplastic thorax (classically bell-shaped/the shape of a champagne bottle cork) is common, which is disproportionately small in relation to the abdomen and results in pulmonary hypoplasia. Sonographically, it can be indicated by cardiac circumference greater than 60% of the thoracic circumference. The normal abdomen may appear protuberant in comparison with hypoplastic thorax. [5],[6],[7]

Generally, the ribs are short, horizontal with flaring of the anterior ends. The scapulae are small. The long bones of the extremities are short and curved. The femora characteristically show telephone receiver configuration. The sonographic criteria regarding the long bones in the diagnosis of TD are severe rhizomelic micromelia with bowing, length of limbs being less than third percentile for gestational age. The metaphyseal ends can have a thorn like projection. The skin appears thick due to extreme redundancy and may prevent normal movement and positioning of limbs causing them to be oriented at right angles to the body. [5],[6],[7]

The spine characteristically shows platyspondyly and H or U configuration of the vertebrae on anteroposterior film due to normal size pedicles of the flattened vertebrae. The height of the intervertebral disc space is up to four times greater than adjacent vertebrae. There may be decreased interpedicular distance in the mid lumbar region. The pelvis characteristically shows decreased vertical height of iliac bones with increased horizontal width. The acetabulae are flat. [8]

TD can present with large calvarium as compared to skull base. The skull can appear trilobed. Approximately, 20% of affected individuals show cloverleaf skull due to primary craniosynostosis. The presence of bulging in the temporal location and bilateral involvement are clues to pick up this diagnosis. [7]

Based on the bone deformity pattern, TD has been divided into two types. Type I is more common and is characterized by curved long bones and severe platyspondylia, usually without a cloverleaf skull. In type II, the long bones are relatively straight, the platyspondylia is less severe, and a cloverleaf skull is usually present. Some clinical overlap exists between the two subtypes. The vast majority of cases are due to denovo mutations. [5]

The genetic basis is thought to be due to autosomal dominant mutation affecting different functional domains of FGFR3 gene. It is proposed by some authors that hypochondroplasia, achondroplasia, and TD are different ends of the FGFR3 mutation with hypochondroplasia being mildest and TD the most severe form. [9]

TD, being a lethal dysplasia, stillbirth or death during neonatal life occurs within minutes or days after birth, usually from respiratory failure or brain stem compression due to underlying hydrocephalus. [10]

The differential diagnosis includes osteogenesis imperfecta type II, which is characterized by fracture of long bones and achondrogenesis characterized by extreme hypomineralization. Other rarer differential diagnosis includes camptomelic dwarfism, chondrodysplasia puncta, and severe hypophosphatasia. [1]

No statistics or registry exists in India to give an actual insight into the problem of congenital malformation and their prenatal diagnosis. It is important to integrate a network of diagnostic testing for proper and early diagnosis of bony dysplasia. Early diagnosis of TD is important since it gives an alternative option of termination of pregnancy when an affected fetus is detected. However, genetic counseling and evaluation of the prognosis on the basis of molecular results should be considered an important issue.

 
  References Top

1.Ldr Sq, Sahu S, Cdr Wg, Kaur P. Thanatophoric Dysplasia: Antenatal Diagnosis. Med J Armed Forces India 2009;65:87-8.  Back to cited text no. 1
    
2.Orioli I, Castilla EE, Barbosa-Neto JG. The birth prevelance rates for the skeletal dysplasias. J Med Genet 1986;23:328-32.  Back to cited text no. 2
    
3.Martínez-Frías ML, Ramos-Arroyo MA, Salvador J. Thanatophoric dysplasia: An autosomal dominant condition? Am J Med Genet 1988;31:815-20.  Back to cited text no. 3
    
4.Budorick NE. The Foetal musculoskeltal ultrasound. In: Peter W Callen, editor. Ultrasonography in Obstetrics and Gynaecology. 4 th ed. Philadelphia: W B Saunders; 2000. p. 343-5.  Back to cited text no. 4
    
5.Chen CP, Chern SR, Shih JC, Wang W, Yeh LF, Chang TY, et al. Prenatal diagnosis and genetic analysis of type I and type II thanatophoric dysplasia. Prenat Diagn 2001;21:89-95.  Back to cited text no. 5
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6.Tsutsumi S, Sawai H, Nishimura G, Hayasaka K, Kurachi H. Prenatal diagnosis of thanatophoric dysplasia by 3-D helical computed tomography and genetic analysis. Fetal Diagn Ther 2008;24:420-4.  Back to cited text no. 6
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7.Parilla BV, Leeth EA, Kambich MP, Chilis P, MacGregor SN. Antenatal detection of skeletal dysplasias. J Ultrasound Med 2003;22:255-8.  Back to cited text no. 7
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8.Pritzker HA, Murray RO. Congenital shortness of stature. The radiology of skeletal disorders. 3 rd ed., vol. II. Edinburgh: Churchill Livingstone; 1990. p. 962-3.  Back to cited text no. 8
    
9.Cohen MM Jr. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: Clinically related skeletal dysplasias that are also related at the molecular level. Int J Oral Maxillofac Surg 1998;27:451-5.  Back to cited text no. 9
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10.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. 10
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