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Table of Contents
Year : 2018  |  Volume : 26  |  Issue : 3  |  Page : 171-173

Skeletal defect at mid-trimester ultrasound scan

1 Department of Obstetrics and Gynaecology, Centro HospitalarTâmega E Sousa; Faculty of Medicine, University of Porto, Porto, Portugal
2 Department of Obstetrics and Gynaecology, Centro HospitalarTâmega E Sousa, Porto, Portugal

Date of Submission28-Dec-2017
Date of Acceptance29-Mar-2018
Date of Web Publication14-Sep-2018

Correspondence Address:
Dr. Pedro Brandao
Department of Obstetrics and Gynaecology, Centro HospitalarTamega E Sousa, Avenida Do Hospital Padre Americo 210, 4564-007, Penafiel, Porto
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JMU.JMU_45_18

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How to cite this article:
Brandao P, Soares E, Estevinho C, Freixo M, Portela-Carvalho AS, Ferreira MJ. Skeletal defect at mid-trimester ultrasound scan. J Med Ultrasound 2018;26:171-3

How to cite this URL:
Brandao P, Soares E, Estevinho C, Freixo M, Portela-Carvalho AS, Ferreira MJ. Skeletal defect at mid-trimester ultrasound scan. J Med Ultrasound [serial online] 2018 [cited 2022 Nov 28];26:171-3. Available from: http://www.jmuonline.org/text.asp?2018/26/3/171/233272

  Section 2 - Answer Top

  Case Description Top

A 25-year-old primigravida was sent to the hospital due to gestational diabetes. First trimester ultrasound (US) scan and combined screening revealed reduced risk for aneuploidies as follows: trisomy 21 (1: 16,185), 18, and 13 (1: 100,000), pregnancy-associated plasma protein A = 3 MoM, free beta-human chorionic gonadotropin = 0.92 MoM, and a nuchal translucency of 2.8 mm (above the 95th centile for gestational age). At the mid-trimester US, the amniotic fluid was slightly increased, the fetus had a head circumference (203 mm), and a biparietal diameter (55.8 mm) above the 95th centile [Figure 1]. The skull had a frontoparietal narrowing (“lemon” sign) [Figure 2], with no apparent intracranial abnormalities. There were an increased cardiothoracic ratio and a clear disproportion between the thoracic and the abdominal diameter (“keel-shaped” or “bell-shaped” trunk) suggesting shortening of the ribs [Figure 3] and [Figure 4]. There was an obvious shortening of the long bones below the 5th centile, including the humerus (16.6 mm), ulna (19 mm) [Figure 5], femur (9 mm) [Figure 6], and fibula (16.5 mm); both the femur and humerus had a slight curvature (telephone receiver shape) [Figure 7]. Face, lungs, heart, abdomen, genitalia, and spine were normal.
Figure 1: Ultrasound: Fetal head circumference and a biparietal diameter above the 95th centile

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Figure 2: Ultrasound: Frontoparietal narrowing (“lemon sign”) of the cranium. No intracranial abnormalities

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Figure 3: Ultrasound: Increased cardiothoracic ratio due to shortening of the ribs and consequent narrowed thorax

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Figure 4: Ultrasound: Disproportion between the thoracic and the abdominal diameter - “keel” or “bell” trunk shape

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Figure 5: Ultrasound: Short ulna (below the 5th centile)

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Figure 6: Ultrasound: Short and curved femur (below the 5th centile)

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Figure 7: Ultrasound: Fetal arm with short long bones

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  Interpretation Top

These US findings suggested a severe and isolated shortening of the long bones, restricting fetal growth, and were highly suggestive of severe skeletal dysplasia.

Skeletal defects are a heterogeneous group of malformations which are found in nearly 1 in 4000 births. Osteochondrodysplasias, defects of cartilage or bone growth, and development are one of the main groups of these pathologies. Some of these entities are thought to be caused by mutations on the fibroblast growth factor receptor 3 (FGFr3) gene located at the short arm of chromosome 4, namely, achondroplasia, hypochondroplasia, and thanatophoric dysplasia (types I and II).[1],[2]

The patient was referred to our prenatal diagnosis department for antenatal counseling and further investigation. At 21 weeks, the patient underwent amniocentesis and at 21 weeks and 2 days pregnancy was terminated.

The postabortion radiographic study confirmed the US findings [Figure 8] and [Figure 9]. The fetus had a decreased body size compared to the head, and a small chest compared to the abdomen. It also confirmed the presence of shortening of the long bones of the limbs and the ribs. The cytogenetic examination revealed a karyotype 46 XY and molecular study by Array-cGH for skeletal dysplasias detected a G (p. Tyr373Cys)-c. 1118A mutation in the FGFr3 gene in heterozygosity, consistent with the phenotype of thanatophoric dysplasia type I.
Figure 8: Anteroposterior postabortion X-ray of the fetus: shortened limbs with bowed bones and flared irregular metaphyses

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Figure 9: Profile postabortion X-ray of the fetus: small long bones, narrowed thorax due to shortened ribs

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Thanatophoric dysplasia is the most common lethal skeletal dysplasia, found in 1 in 10,000-1 in 50,000 births. Its name derives from ancient Greek, meaning death-bearing, as it is almost always incompatible with life (there are some rare case reports of survivors) and the characteristic features are severe shortening of the limbs with several skinfolds, narrow thorax (with consequent increased cardiothoracic ratio), normal or large belly, and prominent forehead (ending up as disproportional abdomen compared to the thorax).[3] Classically, it is divided into two types. In type I, which is sporadic, the femurs are typically curved (“telephone receiver like”) and are not often associated with cloverleaf skull. In type II, which is autosomal recessive, the femurs are straight, and the skull is typically cloverleaf shaped. Type I is thought to be caused by several mutations of the FGFr3 gene, but type II is thought to be caused by a unique mutation.[4]

Usually, skeletal dysplasias may be diagnosed by US during the mid-trimester scan.[5],[6] The most common feature to raise suspicion of these diagnoses is the shortening of the long bones, which is common to all of them. The differential diagnosis between them may not be easy, as their specific features may not be present, or may be subtle.[7],[8]

As a conclusion, in the presence of shortened and bowed fetal long bones, thanatophoric dysplasia should always be ruled out. These fetuses have growth and movement restriction, as well as limited neonatal respiratory capacity, the reason why it is considered a fatal condition. Suspecting this condition during mid-trimester scan is of utmost importance, to allow prenatal diagnosis which may be subsequently confirmed using Array-CGH analysis.

This case highlights the importance of routine examination of the long bones during the mid-trimester scan.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Lemyre E, Azouz EM, Teebi AS, Glanc P, Chen MF. Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: Review and update. Can Assoc Radiol J 1999;50:185-97.  Back to cited text no. 1
Krakow D, Lachman RS, Rimoin DL. Guidelines for the prenatal diagnosis of fetal skeletal dysplasias. Genet Med 2009;11:127-33.  Back to cited text no. 2
Miller E, Blaser S, Shannon P, Widjaja E. Brain and bone abnormalities of thanatophoric dwarfism. AJR Am J Roentgenol 2009;192:48-51.  Back to cited text no. 3
Martínez-Frías ML, de Frutos CA, Bermejo E, Nieto MA; ECEMC Working Group. Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet A 2010;152A: 245-55.  Back to cited text no. 4
Yüce MA, Yardim T, Kurtul M, Durukan S, Gücer F. Prenatal diagnosis of thanatophoric dwarfism in second trimester. A case report. Clin Exp Obstet Gynecol 1998;25:149-50.  Back to cited text no. 5
Schild RL, Hunt GH, Moore J, Davies H, Horwell DH. Antenatal sonographic diagnosis of thanatophoric dysplasia: A report of three cases and a review of the literature with special emphasis on the differential diagnosis. Ultrasound Obstet Gynecol 1996;8:62-7.  Back to cited text no. 6
Chitty LS, Khalil A, Barrett AN, Pajkrt E, Griffin DR, Cole TJ, et al. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat Diagn 2013;33:416-23.  Back to cited text no. 7
Sahinoglu Z, Uludogan M, Gurbuz A, Karateke A. Prenatal diagnosis of thanatophoric dysplasia in the second trimester: Ultrasonography and other diagnostic modalities. Arch Gynecol Obstet 2003;269:57-61.  Back to cited text no. 8


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]

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