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
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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.
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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)
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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
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