SKELETAL DYSPLASIAS: DIAGNOSTICS AND TREATMENT

1
29284
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
2
Introduction
molecular genetic causes
Abnormal biochemical characteristics of essential
bone components collagen, glykosaminoglycans,
hydroxyapatite
CHANGES IN SHAPE AND STRUCTURE OF SKELETON
Functional adaptation of bones (Frost 1995 Utah
paradigma of bone physiology)
Teratogenic influence in critical sensitive
periods of ontogenesis
Hormonal, metabolic enzymatic disorders
3
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.

4
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)
5
Results of comprehensive treatment
1. FGFR-3 group Achondroplasia
Result of lengthening18.5 cm
6
Results of comprehensive treatment
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
7
Results of comprehensive treatment
35. Limb hypoplasia-reduction defects group
Fibular hemimelia
Predicted shortening 25-30 cm
8 cm
18 cm
Result of lengthening 26 cm
8
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 Cobbs angle was 12.
• Bone remodeling laws are true for physeal growth
  of congenital wedge and hemiwedge vertebrae, too.

T12 - 33- L7
T12 - 21- L7
2 yrs.
9
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.

10
Conclusion

• The final shape of skeleton of SD patients is
  consequence of genetic defects, mechanical
  stimuli and functional adaptation of bones.
• Diagnostics of BD is based on clinical,
  anthropological, genetic (including molecular
  genetic) and radiological examination together
  with laboratory examination and dual energy
  densitometry - DXA.
• Radiological diagnostics is possible only in
  growth period.
• Diagnosis of joint systemic disorders is
  necessary as soon as possible.
• The aim of comprehensive care is to prepare
  handicapped children for a dignified, meaningful
  and satisfying life and help them to incorporate
  themselves into society as individuals who can
  achieve their highest potential.
• Authors declare that they have no conflict of
  interests.