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SKELETAL DYSPLASIAS: DIAGNOSTICS AND TREATMENT

I. Marik1, D. Zemkova1,2, M. Kuklik1, R. Myslivec1, S. Petrasova1, O. Hudakova & A. Marikova1

1 Ambulant Centre for Defects of Locomotor Apparatus, Olšanská 7, Prague 3, PC-130 00, Czech Republic

2 Pediatr. Dept, University Hospital Motol, Charles University Prague,

V Úvalu 84, Prague 5, PC-152 00

molecular genetic causes

CHANGES IN SHAPE AND

STRUCTURE OF SKELETON

Abnormal biochemical characteristics of essential bone components: collagen, glykosaminoglycans,

hydroxyapatite

Hormonal, metabolic & enzymatic disorders

Teratogenic influence in critical sensitive periods of

ontogenesis

Functional adaptation of

bones (Frost 1995: Utah paradigma of bone physiology)

Introduction

Patients and Methods• In years 1994 – 2009 in a cohort of 501 patients with

congenital systemic defects of locomotor apparatus the authors diagnosed 101 nosologic units that were categorized into 34 groups of SD (classification according to Superti-Furga A, Unger S, and Nosology Group of the International Skeletal Dysplasia Society. 2007. Nosology and Classification of Genetic Skeletal Disorders: 2006 Revision. Am J Med Genet. Part A 143A: s. 1-18).

• Aims of orthotic and surgical treatment are based on biomechanical knowledge of growth of healthy and dysplastic skeleton, correction of long bones and spine deformities, shortening and/or lengthening of long bones and reconstruction of hand and foot malformations.

• Timing of surgical treatment is influenced by severity of the defects and is different at isolated and systemic defects. The timing is individually indicated with use of anthropological examination and auxological assessment.

Results Diagnostic achievements

In two unrelative families the type 2 Collagenopathy was identified:Arg75Cys mutation (R75C mutation)Czech dysplasia metatarsal type: another type II collagen disorder.

Eur J Hum Genet, 2007, 15: 1269-1275 (Hoornaert, Marik, Kozlowski, Cole, Le Merrer, Leroy, Coucke, Sillence, Mortier)

Results of comprehensive treatment 1. FGFR-3 group: Achondroplasia

Result of lengthening:18.5 cm

11. Spondyloepi-(meta)-physeal dysplasias (SE/M/D) group: SED tarda, X- linked

12 yrs. 2mo.

16 yrs.

Result of partial medial epiphyseodesis of both distal femurs & distal tibias

Results of comprehensive treatment

35. Limb hypoplasia-reduction defects group: Fibular hemimelia Fibular hemimelia

Predicted shortening 25-30 cm

+ 8 cm

+ 18 cm

Results of comprehensive treatment

Result of lengthening: 26 cm

Results of orthotic treatment• Hemivertebra L2 & L5 on the right side • The special brace with regulated bending pre-stressing, regime 23

hours. After 20 months of bracing correction of Cobb´s angle was 12°. • Bone remodeling laws are true for physeal growth of congenital

wedge and hemiwedge vertebrae, too.

T12 - 33°- L7 T12 - 21°- L72 yrs.

Discussion• Skeletal dysplasias or disorders (SD) comprise the main part of constitutional

disorders of skeleton. Incidence is estimated 0.30 – 0.45 per 1000 live birth. In last 10 years, rapid advances have been made in identifying chromosomal locus and/or the molecular changes responsible for definition of conditions that help further understand the pathogenesis of individual disorders.

• Skeletal and joint deformities or malformations are considered as arthritic disposition and lead to biomechanical severe deformities of skeleton with premature osteoarthritis and osteoporosis.

• Medicament therapy is suitable only exceptionally at some metabolic osteopathies. Symptomatic treatment of skeletal dysplastic deformities in childhood is early correction of both bone deformities (by physiotherapy, bracing, surgical procedures, etc.) and bone metabolism (e.g. calciotropic drugs) with the aim to achieve an individual ideal peak bone mass and optimal biomechanical properties of skeleton in adulthood.

Conclusion• The final shape of skeleton of SD patients is The final shape of skeleton of SD patients is

consequence of genetic defects, mechanical stimuli and consequence of genetic defects, mechanical stimuli and functional adaptation of bones.functional adaptation of bones.

• Diagnostics Diagnostics of BD is based on clinical, anthropological, of BD is based on clinical, anthropological, genetic (including molecular genetic) and radiological genetic (including molecular genetic) and radiological examination together with laboratory examination and examination together with laboratory examination and dual energy densitometry - DXA.dual energy densitometry - DXA.

• Radiological diagnostics is possible only in growth Radiological diagnostics is possible only in growth period.period.

• Diagnosis of joint systemic disorders is necessary as Diagnosis of joint systemic disorders is necessary as soon as possible. soon as possible.

• The aim of The aim of comprehensive carecomprehensive care is to prepare is to prepare handicapped children for a dignified, meaningful and handicapped children for a dignified, meaningful and satisfying life and help them to incorporate themselves satisfying life and help them to incorporate themselves into society as individuals who can achieve their highest into society as individuals who can achieve their highest potential. potential.

• Authors declare that they have no conflict of interests.