Skeletal Dysplasia: A prenatal Diagnostic Challenge

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Author information

Niphadkar M*, Parulekar SV**

(* Second year resident, ** Professor and Head, Department of Obstetrics and Gynecology, Seth G.S medical college and KEM hospital, Mumbai, India)

Abstract

Skeletal dysplasias are a very wide and diverse group of conditions related to abnormal bone growth and development. The prenatal diagnosis by ultrasound is  challenging due to wide variety of clinical manifestations and changes occurring due to advancing gestational age. Most of these babies are born at  or near term. Here we report an image of a second trimester fetal demise with the abortus having  abnormally short limbs.

Introduction

The most common type of lethal skeletal dysplasia occurring in the neonatal period is thanatophoric dyplasia. ¹ These conditions pose a challenge for antenatal sonography diagnosis because of large number of dysplasias, variability in time at which the features appear, phenotypic variability with overlapping features and lack of molecular diagnosis.

Case Report

A 24 year old woman, married for 9 years (non-consanguineous marriage) , gravida 5, para 3, living 2, abortion 1, neonatal death 1 presented with 5 months of amenorrhea. She was referred from a private hospital in view of ultrasonography suggestive of intrauterine fetal demise at 14.5 weeks with malformed fetal limbs. The patient had no complaints of pain in abdomen, bleeding per vaginum, any bowel or bladder disturbances. She had no history of any significant medical or surgical illness. Obstetric history was significant, as follows:

G_1:  female of 6 years, full term normal delivery (FTND)

G_2:  female who died on day 1 of FTND. Patient gave history that the baby had absent proximal limb bones.

G_3:  male of 1.5 years, FTND.

G_4:  spontaneous abortion at 2 month amenorrhea, check curettage was done

G_5:   present pregnancy 

The pregnancy was terminated by induction with tablet Misoprostol 400 μg per vaginally 4 hourly. The patient aborted with three doses. The abortus was found to have abnormally short limbs (figure 1).

Figure 1. Abortus with hupoplastic upper limbs.

It showed short, stunted limbs, apparently missing proximal limb bones, without polydactyly or syndactyly. It was somewhat macerated and its sex could not be determined. Its long bones could not be assessed due to very less gestational age of the abortus. Fetal karyotyping and fetal biopsy could not be done due to maceration of tissues. After considering the history and examination of the abortus, the most probable diagnosis of thanotophoric dysplasia, though osteogenesis imperfecta type 2, achondroplasia and other less common dysplasias could not be ruled out with certainty. The patient was explained regarding the autosomal dominant inheritance of the condition resulting in 2 of her pregnancies getting affected and was advised to avoid consanguineous marriages of her children to avoid the future generations being affected by the condition.

Discussion

Skeletal dysplasias are a wide heterogeneous group of conditions caused by disturbances of bone growth, beginning in the early stages of fetal development and evolving throughout life due to active gene involvement.^[1] The  osteochondrodysplasias  are  disorders  of  development  and/or  growth  of  cartilage and/or  bone, causing affection of long  bones  in  a  generalized and symmetric  manner  and dwarfism. Various causes include thanatophoric dwarfism, achondrogenesis, amelia, osteopetrosis, cleidocranial dysplasia, Ellis-van Creveld syndrome, short rib polydactyly syndrome, Jarcho Levin syndrome, femoral hypoplasia – unusual face syndrome, Ol type 1-3, spondyloepiphyseal dysplasia congenital, SADDAN, fibrochondrogenesis etc.^[1,2] Prenatal diagnosis may be possible with ultrasonography (long bone measurements at or less than the 5th centile or >3 SD below the mean.^[3,4] Perinatal lethality can be assessed by ultrasonographic chest circumference to abdominal circumference ratio (<0.6) and/or femur length to abdominal circumference measurement ratio (0.16). ^[3] Molecular testing helps identify homozygosity or compound heterozygosity. Potdelivery/postmortem diagnosis can be done with radiography, autopsy, histopathology and Immunohistochemistry. ^[3,4] However if a patient aborts, the clinicians need to have knowledge of the appearance of such fetuses so that the abortus can be studied further. The published literature does not have many images of such abortuses. Hence this image is presented.

References

1. Dighe M, Fligner C, Cheng E, Warren B, Dubinsky T. Fetal Skeletal Dysplasia: An Approach to Diagnosis with Illustrative Cases. RSNA RadioGraphics 2008;28(4). DOI: http://dx.doi.org/10.1148/rg.284075122
2. Krakow D, Rimoin DL. The skeletal dysplasias. Genetics in Medicine 2010;12:327–341.
3. Krakow D, Lachman RS, Rimoin DL. Guidelines for the prenatal diagnosis of fetal skeletal dysplasias. Genet Med. 2009;11(2): 127–133. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832320/
4. Gnoli M, Pedrini E, Mordenti M, Tremosini M, Sangiorgi L. Skeletal dysplasias: approach to the clinical diagnosis and implication of appropriate diagnosis for knowledge and research studies in these rare diseases. Hereditary multiple Osteochondromas as example/paradigm. Italian Journal of Pediatrics 2014;40(Suppl 1):A8  doi:10.1186/1824-7288-40-S1-A8 Available from: http://www.ijponline.net/content/40/S1/A8

Citation

Niphadkar M, Parulekar SV. Skeletal Dysplasia: A prenatal Diagnostic Challenge. JPGO 2015. Volume 2 No. 2. Available from:  http://www.jpgo.org/2015/02/skeletal-dysplasia-prenatal-diagnostic.html