A full-term infant with type II thanatophoric dysplasia

Natharina Yolanda 1 , Ferry Yulianto 2 , Sally Arina 2 , and Johanes Edwin 3
  • 1 Bunda Aliyah Maternity Hospital, Jl. Pahlawan Revolusi No 100, Pondok Bambu, Jakarta Timur, Indonesia
  • 2 Bunda Aliyah Maternity Hospital, Jakarta, Indonesia
  • 3 Department of Child Health, Bunda Aliyah Maternity Hospital, Jakarta, Indonesia
Natharina Yolanda
  • Corresponding author
  • Bunda Aliyah Maternity Hospital, Jl. Pahlawan Revolusi No 100, Pondok Bambu, Jakarta Timur, Indonesia
  • Email
  • Search for other articles:
  • degruyter.comGoogle Scholar
, Ferry Yulianto, Sally Arina and Johanes Edwin

Abstract

Objectives

To report a neonate with clinical findings consistent with thanatophoric dysplasia (TD). Only a few cases of this rare and lethal skeletal disorder have been reported in South-East Asia.

Case presentation

A 37-year-old Asian female, fourth gravida at 39 weeks, presented to our hospital for an elective cesarean section due to polyhydramnios, frank breech and gestational hypertension. The father was a 42-year-old Asian male. There was no history of rashes, fever, alcohol intake, substance drug abuse, smoking habit or radiation exposure. Ultrasound (US) of 34-weeks’ gestation found a baby with frontal bossing, prominent temporal lobe, clover-skull and low nasal bridge. The thoracic diameter was smaller than the abdominal diameter. Short limbs without bowing were noted in femur and humeral bones. The patient delivered a baby boy, 4115 g, APGAR scores were 5 and 7 at 1 and 5 min. The baby had a dysmorphic face, frontal bossing, low nasal bridge, low-set ears and short neck. The thorax was narrow and abdomen was protuberant. The upper and lower proximal limbs appeared short. A chest X-ray revealed short, curved ribs and opacification of both lungs. He had respiratory distress shortly after birth and had persistent severe respiratory distress despite adequate mechanical ventilation. On the third day, he had cardiac arrest; resuscitation was not done due to family request. The baby was declared deceased due to cardiopulmonary failure related to his congenital anomaly.

Conclusions

Ultrasonography could readily indicate TD prenatally. The pregnancy can continue up to late third trimester without miscarriage. Most of the neonates die in utero; those who survive are dependent on ventilator.

  • [1]

    Miller E, Blaser S, Shannon P, Widjaja E. Brain and bone abnormalities of thanatophoric dwarfism. Am J Roentgenol. 2009;192:48–51.

    • Crossref
    • Export Citation
  • [2]

    Maroteaux P, Lamy M, Robert JM. Le nanisme thanatophore. Presse Med. 1967;75:2519.

  • [3]

    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.

    • Crossref
    • PubMed
    • Export Citation
  • [4]

    Foldynova-Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Hum Mutat. 2012;33:29–41.

    • Crossref
    • PubMed
    • Export Citation
  • [5]

    Vogt C, Blaas HGK. Thanatophoric dysplasia: autopsy findings over a 25-year period. Pediatr Dev Pathol. 2013;16:160–7.

    • Crossref
    • Export Citation
  • [6]

    Chitty LS, Mason S, Barrett AN, McKay F, Lench N, Daley R, et al. Non-invasive diagnosis of achondroplasia and tanathophoric dysplasia: next-generation sequencing allows for a more accurate, and comprehensive approach. Prenat Diag. 2015;35:656–62.

    • Crossref
    • Export Citation
  • [7]

    Mayoral EE, Schultz R, Rosember S, Suzuki L, de Oliveira LA, Kay FU. Thanatophoric dysplasia: case report of an autopsy complemented by postmortem computed tomographic study. Autop Case Rep. 2014;4:35–41.

    • Crossref
    • Export Citation
  • [8]

    Wiener-Megnazi Z, Auslender R, Dirnfeld M. Advanced paternal age and reproductive outcome. Asian J Androl. 2012;14:69–76.

    • Crossref
    • PubMed
    • Export Citation
  • [9]

    Khalil A, Pajkrt E, Chitty LS. Early prenatal diagnosis of skeletal anomalies. Prenat Diang. 2011;31:115–24.

    • Crossref
    • Export Citation
  • [10]

    Wong HS, Kidd A, Zucollo J, Tuohy J, Strand L, Tait J, et al. A case of thanatophoric dysplasia: the early prenatal 2D and 3D sonographic findings and molecular confirmation of diagnosis. Fetal Diagn Ther. 2008;24:71–3.

    • Crossref
    • PubMed
    • Export Citation
  • [11]

    Yeh P, Saeed F, Paramasivam G, Wyatt-Ashmead J, Kumar S. Accuracy of prenatal diagnosis and prediction of lethality for fetal skeletal dysplasias. Prenat Diagn. 2011;31:515–8.

    • Crossref
    • PubMed
    • Export Citation
  • [12]

    Martinez-Frias ML, Frutos CA, Bernejo E, Nieto A. Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and the potential therapeutic implications for anchondroplasia. Am J Med Genet A. 2010;152A:245–55.

    • Crossref
    • PubMed
    • Export Citation
  • [13]

    Martinez-Frias ML, Egues X, Puras A, Hualde J, de Frutos CA, Bermejo E, et al. Thanatophoric dysplasia type II with encephalocele and semiobar holoprosencephaly: insights into its pathogenesis. Am J Med Genet A. 2010;155:197–202.

  • [14]

    Li D, Liao Can, Ma X, Li Q, Tang X. Thanatophoric dysplasia type 2 with encephalocele during the second trimester. Am J Med Genet. 2006;140:1476.

  • [15]

    Tavorima 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.

    • Crossref
    • PubMed
    • Export Citation
  • [16]

    Reardon W. The bedside dysmorphologist, classic clinical signs in human malformation syndromes and their diagnostic significance. USA: Oxford University Press; 2008.

  • [17]

    Baker KM, Olson DS, Harding CO, Pauli RM. Long-term survival in typical thanatophoric dysplasia type I. Am J Med Genet. 1997;70:427.

    • Crossref
    • PubMed
    • Export Citation
  • [18]

    Jin M, Yu Y, Qi H, Xie Y, Su N, Wang X, et al. A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia. Hum Mol Genet. 2012;21:5443–5.

    • Crossref
    • PubMed
    • Export Citation
  • [19]

    Wilkinson DJC, Thiele P, Watkins A, De Crespigny L. Fatally flawed? A review and ethical analysis of lethal congenital malformations. Br J Obstet Gynaecol. 2012;119:1302–8.

    • Crossref
    • Export Citation
Purchase article
Get instant unlimited access to the article.
$42.00
Log in
Already have access? Please log in.


or
Log in with your institution

Journal + Issues

Search