Balkan Journal of Medical Genetics

CHARACTERISTIC DIAGNOSTIC CLUES OF METATROPIC DYSPLASIA: THE LUMBOTHORACIC HUMPBACK WITH DUMBBELL APPEARANCE OF THE LONG BONES
Gucev Z, Kalcev G, Laban N, Bozinovski Z, Popovski N, Saveski A, Daskalov B, Plaseska-Karanfilska D, Tasic V
*Corresponding Author: Professor Zoran Gucev, Department for Endocrinology and Genetics, University Children’s Hospital, Medical Faculty Skopje, Majka Teresa BB, Skopje 1000, Republic of Macedonia. Tel.: +389-70-279-742. Fax: +389-3-226-356. E-mail: gucevz@gmail.com
page: 35

INTRODUCTION

Metatropic dysplasia (MD; OMIM 156530) is a bone dysplasia with severe kyphoscoliosis and platyspondyly, severe metaphyseal enlargement, short stature and shortening of long bones [1]. The incidence of this disorder is not known, as less than a hundred cases have been reported so far [2,3]. Transient receptor potential vanilloid 4 channel (TRPV4) is a cation channel, unselectively permeable to calcium and widely expressed and involved in many different physiological processes. Strikingly heterozygous missense mutations of the TRPV4 gene cause several skeletal syndromes: brachyolmia, spondylometaphyseal dysplasia Kozlowski type, metatropic dysplasia, parastremmatic dysplasia, familial digital arthropathy and spondyloepimetaphyseal dysplasia Maroteaux type. On the other hand, heterozygous TRPV4 missense mutations cause peripheral neuropathy, hereditary motor and sensory neuropathy type IIC, congenital distal spinal muscular atrophy, and scapuloperoneal spinal muscular atrophy [4]. A concominant existence of bone dysplasia and neuropathy was also observed: fetal akinesia, understood as a form of neuropathy, was found in four patients with MD [5]. This report describes an unusual presentation of MD in a boy referred for knock-knees presumed to be a rickets sequel. Patient Report. The proband was born to non consanguineous parents after an uneventful pregnancy, with no infections, smoking, medications or narcotics. The delivery was timely and uneventful. There was no family history of skeletal disorders. This 28-month-old boy with knock-knees was referred for metabolic investigation for a suspected vitamin D-resistant rickets. He got regular vitamin D prophylaxis at an appropriate dose. There was a mid-face hypoplasia with frontal bossing, his mental development was normal, but he started to walk late at the age of 22 months. On physical examination, he had knock-knees, long and narrow thorax, kyphoscoliosis (Figure 1). His height was -3.5 SDS and for his age. Laboratory investigations revealed normal values for calcium, phosphorus and alkaline phosphatase. An X-ray of the skeleton revealed platyspondyly, anteriorly rounded vertebral bodies, dysplastic metaphyses with dumbbell appearance of the long bones, kyphoscoliosis, narrow and elongated thorax with short ribs suggestive for a mild form of MD [Figure 2(A) and 2(B)]. There was significant metaphyseal widening of the long bones of the upper [Figure 2(C)] and lower [Figure 2(D)] extremities, halberd-shaped proximal femurs, wide ilia, and hypoplastic acetabular roofs. The epiphyses were flat and quite hypoplastic throughout and the phalanges were short and widened. The diagnosis of MD in this patient was further confirmed by direct DNA sequencing of the TRPV4 gene and the discovery of the c.2396C>T, p.Pro799Leu (P799L) mutation in a heterozygous state (Figure 3). As the parents did not carry the mutation, the mutation in the proband has arisen as a de novo event.

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