CASE PRESENTATION ACHONDROPLASIA CASE REPORT

ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI MEDICINĂ FASCICULA XVII, no.1, 2015 CASE PRESENTATION ACHONDROPLASIA ‒ CASE REPORT Michaela Dobre1, Bia...
Author: Barry Floyd
1 downloads 0 Views 377KB Size
ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI MEDICINĂ FASCICULA XVII, no.1, 2015

CASE PRESENTATION ACHONDROPLASIA ‒ CASE REPORT Michaela Dobre1, Bianca I. Chesaru1, M.E. Georgescu2, Aurelia Romila1, Victorita Stefanescu1 1

Faculty of Medicine and Farmacy, Dunărea de Jos University of Galati 2 Centre Hospitalier Universitaire Trousseau, Tours, France [email protected]

ABSTRACT Achondroplasia is a hereditary genetic disorder, characterized by an abnormal development of the bones, manifested by dwarfism and disproportionally short limbs compared to the rest of the body. This disease is triggered by a mutation of the FGFR3 gene. Limb lengthening may be indicated in patients with achondroplasia who want to reach an average height of the population they belong. This paper presents the case of a patient diagnosed with achondroplasia who underwent limb lengthening surgical procedure. KEYWORDS: achondroplasia, fibroblast growth factor receptor-3, dwarfism, limb lengthening

have achondroplasia as the result of a de novo gene

1. Introduction

mutation. The prevalence is approximately 1 in 25.000

Achondroplasia [OMIM 100800], described by

[2,4,5].

Dr. Parrot in 1879, is the most common form of

The

dwarfism and most common skeletal dysplasia [1].

diagnosis

established

This autosomal dominant disorder is triggered to a

by

of

typical

achondroplasia clinical

can

findings

be and

radiographic features. Characteristic features include

mutation in the fibroblast growth factor receptor-3

short stature, a relatively large head with frontal

(FGFR3) gene (locus 4p16.3). The gene encodes for a

bossing

member of the FGFR subfamily of tyrosine kinase

and

midface

hypoplasia,

rhizomelic

shortening of the limbs, trident hands, muscular

receptors, which results in constitutive activation of

hypotonia,

the receptor. The FGFR3 is a negative regulator of

and

thoracolumbar

kyphosis.

The

achondroplasic dwarfism is "disharmonious" or

chondrocytes proliferation and differentiation in

"disproportionate", specifically targeting the limbs, in

growth plate. The mutation induces a disturbance of

contrast to other "harmonic" dwarfisms that affect

endochondral bone formation. [2,3] The penetrance

proportionately whole

of the gene is 100%. Over 80% of individuals with

skeleton [5,6].

diagnosis is confirmed by genetic tests. [7]

achondroplasia have parents with normal stature and

93

Accurate

ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI

The patients affected by achodroplasia are monitored

by

anthropometric

FASCICULA XVII

At the age of 1 year and 10 months,

parameters

endocrinological diagnosis made by National Institute

measurements (growth and head circumference, using

of Endocrinology C.I. Parhon from Bucharest was

specific

metaphyseal dysplasia. Patient registered a waist of

standardized

curves)

[8],

periodic

neurological controls (CT, MRI), foramen magnum

78 cm.

surgical enlargement in cases of severe stenosis,

In the next two years, subject’s parents initiate a

middle ear infections treatment. It is recommended to

correspondence with Russian Scientific Center of

maintain weight control since childhood because

Orthopaedics

obesity exacerbates skeletal and joint deformities [9].

Ilizarov" (Kurgan, Russia) in view of lower limb

Growth hormone therapy is still experimental [10].

lengthening procedure. Russian specialists suggested

The management of achondroplasia includes limb

the possibility of surgery procedure performance after

lengthening

the patient reaches 7 years old.

procedures,

tibial

osteotomy

or

and

Traumatology

"Acad.

G.A.

epiphysiodesis of the fibular growth plate to correct

Antropometric monitoring was undertooked for

bowing of the legs, lumbar laminectomy for spinal

patient between 3 and 13 years (Table I), including

stenosis which typically manifests in early adulthood

the determination of Manouvrier index (M), as the

[9].

ratio of leg length to trunk height [11], following formula:

2. Case presentation

M = (H - T) / T (H = total heigh, T = trunk length, measured as sitting

V.D., male patient, 3300g and 52cm at birth,

height).

postnatal growing unsatisfactory, was diagnosed with

Considering values over 0.75 as normal along

achondroplasia after the first year of life.

infance and puberty [12], studied patient registered

At the age of 5 months, the patient was

low values for the Manouvrier skeling ratio (0.60-

hospitalized for febrile condition. Investigations showed

anaemia

(hemoglobin

8.4g%)

0.71).

with

The control carried out at the age of 11 recorded

hypochromia, anisocytosis with microcytosis, and

anthropometric data for the patient as a waist of 123

leukocytosis (14.000/mm3). A lumbar punction was

cm and a weight of 30.5 kg. Radiographs revealed the

performed. Patient was diagnosed with pharingitis,

presence of open growth plates (Figure 1).

anemia, rickets, and exudative diathesis. After treatment,

patient

was

discharged

in

slightly Table I. Evolution of the Manouvrier scale

improved condition. At the age of 10 months, the patient returns with rickets

sequelae.

Anthropometric

Hydrocephalus

and

Height (cm)

Lower limbs (cm)

Bust (cm)

Manouvier index

3 4 5 6 7 8 9 10 11 12 13

88 93 100 105 107 112 115 117 120 124 130

33 37 39 42 44 46 48 49 51 53 54

55 56 61 63 63 66 67 68 69 71 76

0.60 0.66 0.64 0.67 0.70 0.70 0.72 0.72 0.74 0.75 0.71

measurements

revealed a weak trunk and a head circumference of 48cm.

Age (years)

pituitary

dwarfism

diagnosis were suspicioned. No abnormalities were reported at skull Rx but the radiographs of long bones raised the suspicion of achondroplasia. One month later, neurosurgical investigation revealed a cranial perimeter of 49cm and achondroplasia diagnosis was sustained. The patient was directed to endocrinology.

94

ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI

FASCICULA XVII

At the request of parents, Necker University Hospital for sick children from Paris accepted limb lengthening surgical procedure. The diagnosis at presentation was achondroplasia and left Genu Varum. Preoperative, medical examination registered 142 and 80 cm for standing and, respectively, seated heights for the 16 years old patient. Surgical intervention concerned low limbs: an external

a b Figure 1. Hand and knee X-ray at 11 years old

T-shaped

fixator,

with

two

cortical

metapyseal and two cortical diaphyseal screws were fixed in tibia bone;

a.

b.

c.

Figure 2. Radigraphs showing the length gain on the calf bones (a,b,c) and the ossification process (c) the peroneum bone was fixed with a screw through an external incision; a tibial osteotomy was made between the proximal diaphysis and epiphyis; the peroneum was sectioned at 1 cm above the fixation screw. The procedure began with an initial gain of 7 mm, induced by the fixators. It was recommanded a lenghtening of the bones by a daily gain of 1 mm (one-quarter turn of the external key, 4 times daily) for 96 days. The total lenght gain of the calf bones after the procedure was 87 mm. The lenghtening progress and the ossification processes can be observe in figures 2a-c. The fixators were removed after 9

Figure 3 Femur lengthening and ossification

months.

(X-Ray)

95

ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI

FASCICULA XVII

Encouraged by the first achievement, a second

Limb lengthening is a complex procedure with a

intervention, concerning femur lenghtening, was

high rate of complications. Formation of callus is

started half year later. The fixators were removed

influenced by periosteal and endosteal conditions and

after another eleven months. The bones reached

intrinsic factors such as age, systemic disease, the

uneven lengths: 110 mm for the left femur and 115

corticomedullary ratio, previous injury or operation,

cm for the right femur was 115 mm. The fixation

tumours and the vascularity of the surrounding tissues

screws and the correction of the femur can be

[16]. Children with achondroplasia tend to regenerate

observed in figure 3.

the bones faster than normal. Premature consolidation will arrest the lengthening process [16]. However, an increased rate of lengthening may be associated with

3. Discussions

further complications, particularly adjacent to joint stiffness and fractures [13, 17].

Achondroplasia is a condition which restricts

In our case report, patient acquired about 20cm

quality of life often through stigmatisation. People

in height. The patient's psychological benefit resulted

with achondroplasia have short stature, with an

in increased self-confidence due to height increasing.

average adult height of 131cm (52in) for males and

Radiological surveillance of callus formation

123cm (48in) for females – although, technically, for

has proved to be a useful method of evaluation and

an adult man or woman, a maximum of 148cm

monitoring of bone regeneration.

(58.2in) is also considered achondroplastic [6]. Reconstructive surgery is a technique available to

4. Conclusions

these patients. (Lower) limb lengthening is a surgical concept allowing achievement of physiological

Achondroplasia is a severe genetic disorder

proportions. [13,14] Limb lengthening in dwarfism has been termed

affecting the harmonious development of children’

as extensive limb lengthening (ELL). This treatment

bodies. The physical aspect can be surgically

is controversed in USA and Canada but it is well-

improved in order to allow patient having a normal

accepted in dwarfism management in Europe, Asia,

social and day-by-day life. The decision to undergo

and South America along with the introduction of

limb lenghtening is a personal one and it is not for

Ilizarov’s devices. The benefits from ELL may be

every family or child. Despite the difficulties imposed

evaluated in terms of functional, psychosocial and

by achondroplasia, the patients can successfully adapt

therapeutic

to the social conditions, with the ability to undertake

conditions.

The

functional

benefits

the same activities as a healthy person.

derived both from the increase stature and accessing of the reach. Psychological benefits consist especialy to a complete change in body image. The trunk limbs

References

and rhizomelic disproportions are less pronounced.

1. Parrot J.M. Les malformations achondrodysplasiques et le dieu Ptah. In: Bulletins de la Société d'anthropologie de Paris, 1878; 1:296 in: Gorlin RJ, Cohen M Jr., Hennekam RCM, Syndromes of the Head and Neck, Oxford University Press, USA, 2001; 197. 2. Richette P., Bardin T., Stheneur C. Achondroplasia: from genotype to phenotype. Joint Bone Spine. 2008;75(2):125-30. 3. Horton W.A. Recent milestones in achondroplasia research, Am J Med Genet. 2006, 140A:166-169. 4. Wynn J., King T.M., Gambello M.J., Waller D.K., Hecht J.T. Mortality in achondroplasia study: A 42-year follow-up, Am J Med Genet 2007; A143(21): 2502-11.

ELL has some prophylactic and therapeutic benefits: hyperlordosis reduction can reduce spinal stenosis; knee alignment can reduce the onset of arthritis, both on knee and hip level [15].

96

ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI

5. Horton W.A., Hall J.G, Hecht J.T. Achondroplasia, The Lancet. 2007; 162-172. 6. Trotter T.L., Hall J.G. American Academy of Pediatrics Committee on Genetics, Health supervision for children with achondroplasia. Pediatrics. 2005;116(3):771-83. 7. Carter E.M., Davis J.G., Raggio C.L. Advances in understanding etiology of achondroplasia and review of management. Curr Opin Pediatr. 2007; 19(1):32-7. 8. Hoover-Fong J.E., McGready J., Schulze K.J., Barnes H., Scott C.I. Weight for age charts for children with achondroplasia. Am J Med Genet. 2007; 143A: 2227-2235. 9. Horton W.A., Hecht J.T., Chap. 23, Part I-II, Chondrodysplasias. In: Royce P.M., Steinmann B., Connective Tissue and Its Heritable Disorders. Molecular, Genetic, and Medical Aspects. 2nd Ed., Wiley-Liss, New York. 1993; 901-939. 10. Shohat M., Tick D., Barakat S., Bu X., Melmed S., Rimoin D.L., Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia. J Clin Endocr Metab 1996; 81:4033-4037. 11. Tomaszewski P., Gajewski J., Lewandowska J. Somatic Profile of Competitive Sport Climbers. Journal of Human Kinetics. 2011;29:107-113. 12. Sempé M. Accroissements. Auxiometrie. Mesures somatiques courantes en puériculture et pédiatrie. [online]. Accessed 12.05.2015. http://www.accroissements-michel-sempey.fr/images/ stories/Auxiometrie/Chapitre_3/amst.g.iii.06.12--sk.m%20_1.jpg 13. Venkatesh K.P., Modi H.N., Devmurari K., Yoon J.Y., Anupama B.R., Song H.R. Femoral lengthening in achondroplasia. Magnitude of lengthening in relation to patterns of callus, stiffness of adjacent joints and fracture. J Bone Joint Surg [Br] 2009;91-B:1612-17. 14. Schiedel F., Rödl R. Lower limb lengthening in patients with disproportionate short stature with achondroplasia: a systematic review of the last 20 years, Disability and Rehabilitation, 2012; 34(12); 982‒987. 15. Rozbruch S.R., Ilizarov S., Limb Lengthening and Reconstruction Surgery, CRC Press, 2006;575‒596; ISBN 1420014013, 9781420014013 16. Paley D., Problems, obstacles, and complications of limb lengthening by the Ilizarov technique. Clin Orthop 1990; 250:81104. 17. Solomin L., The Basic Principles of External Skeletal Fixation Using the Ilizarov Device, Springer Science & Business Media, 2008;225‒228.

97

FASCICULA XVII

ANALELE UNIVERSITĂŢII “DUNĂREA DE JOS” GALAŢI

98

FASCICULA XVII