Cas de la semaine # 4126 juin 2017

Préparé par Dre Katia Achour, R4

Dr Thomas Moser MD

CHUM

Département de radiologieFaculté de médecine

Histoire Clinique

• Chute sur la main gauche

• Aucun antécédent spécifié

Ø Radiographie du poignet pour éliminerfracture

74 ans

Rx poignet G

Imagerie complémentaire:Radiographies abdominales

RX poignet G

• Aspect de « bone within a bone » (os dans l’os) des os du carpe

• Alternance de bandes radio-denses et radio-transparentes

• Pas de fracture ni luxation

Diagnostic différentiel “ os dans l’os ”

• Infarctus osseux: anémie falciforme / thalassémie

• Ostéopétrose de l’adulte

• Paget

• Maladie de Gaucher

• Exposition à des métaux lourds (bismuth, plomb, thorium)

• Hyperparathyroïdie secondaire

• Acromégalie

• Post radiothérapie

• Syphilis congénitale

• Hyper vitaminose D

• Maladie de Caffey

ü Aspect très dense des structures osseuses ü Vertèbres en sandwichü Séquelles post traumatiques avec réparation de la hanche gauche

Diagnostic final

Ostéopétrose autosomiquedominante bénigne de l’adulte- aussi appelée maladie d’Albers-Schonberg

Dysplasies osseuses sclérosantesCLASSIFICATION

• Ostéopétrose

• Pyknodysostose

• Ostéopoikilose

• Ostéopathie striée

• Dysplasie progressive diaphysaire

• Sclérose diaphysaire multiple héréditaire

• Hyperostose corticale généralisée

• Ostéosclérose intramédullaire

• Mélorhéostose

• Syndromes « overlap »

HÉRÉDITAIRES NON-HÉRÉDITAIRES

DYSPLASIES SCLÉROSANTESACQUISES

• Métastases• Paget• Myélofibrose• Edheim-Chester• Anémie falciforme

OstéopétroseMaladie héréditaire résultant d’un déficit des ostéoclastes

• Ceci crée un défaut du remodelage osseux • La production osseuse n’est pas altérée, d’où un aspect plus sclérotique • Les os sont très fragiles et sujets aux fractures • Aussi appelée « marble bone disease» (le marbre est dur mais fragile)

4 types génétiques

- Ostéopétrose autosomique récessive de l’enfance: maligne

- Ostéopétrose autosomique dominante « bénigne » de l’adulte

- Forme intermédiaire

- Maladie Sly: déficit en anhydrase carbonique II

ü calcifications cérébrales et acidose tubulaire

Physiopathologie

Inactivation du gène Mutation homozygote du Déficit du gène codant pourrégulateur 1 des canal chloride 7 une protéine transmembranaire lymphocytes T essentielle au fonctionnement

des ostéoclastes

Nombre élevé (ou normal) d’ostéoclastes dont la fonction d’acidification toutefois est défectueuse

Défaut de résorption de la matrice osseuse

Adapté de Lauren L. Radiographics 2011.

3 principales mutations génétiques peuvent mener à une ostéopétrose :

Ostéopétrose « bénigne » de l’adulteForme autosomale dominante

Type 1 :• Atteinte de la voute crânienne, pas la base

• Pas d’atteinte du squelette appendiculaire

• Pas d’atteinte du rachis

Type 2 : plus fréquente• Atteinte de la base du crâne, pas la voute

• Atteinte du squelette appendiculaire

• Atteinte du rachis (vertèbres en sandwich)

• Fréquence 1 / 20,000, avec pénétrance variable

• Fractures multiples presque toujours présentes

• Compression des nerfs crâniens plus rare, selon sévérité

• Hépatosplénomégalie

• PancytopénieRares, selon sévérité de l’insuffisance médullaire

Trouvailles radiographiques

Ostéosclérose diffuse

Bone within a bone (classique de la forme adulte)

Déformation en Erlenmeyer des os longs

Vertèbre sandwich

Bandes métaphysaires radiotransparentes

6 Case Reports in Dentistry

Figure 10: Anteroposterior view of the hip joint showed generalisedsclerosis of the pelvic rami and the femur bone.

Figure 11: Radiograph of the humerus showing osteosclerosis ofthe humerus and scapula and typical “funnel-like appearance”(Erlenmeyer-flask deformity) in the humerus.

Figure 12: Anteroposterior view of radius and ulna showingincreased radiodensity in all the bones, smoothening of the bonesurfaces, and cylindrical appearance of the metacarpals.

Figure 13: Panoramic radiograph of the patient’s brother.

patients were ≤18 years of age and 43 patients were >18 yearsof age [21].

The incidence of autosomal dominant osteopetrosis typeII is reported to be the same for males and females. However,55% of the patients reported by Del Fattore et al. were malesand 45% of the patients were females [19]. Waguespack et al.reported a male predominance in their study too [21]. Ourpatient was a 35-year-old female.

Most individuals diagnosed with autosomal dominantosteopetrosis type II have an affected parent, although inour case the family history was unclear, and a panoramicradiograph of the patient’s brother was performed which wasnormal.

ADO type II has an extremely heterogeneous courseranging from an asymptomatic to a severe phenotype [22].Clinical manifestations of ADO type II are dominatedby long-bone fractures [19]. Other classic manifestationsof ADO type II include hip osteoarthritis, scoliosis, andosteomyelitis, particularly affecting the mandible. Cranialnerve compression is a rare complication [23].

Clinical manifestation in the form of diffuse pain wasreported in 30%of the patients byDel Fattore et al. with ADOtype II and fractures in ≤3 bones was reported in 20% of thepatients. 10% of the patients reported fractures in 4–10 bones,and more than 10 bones were fractured in 15% of the patients[19]. Fracture was the most prevalent clinical manifestationsoccurring in 84% of all ADO type II subjects reported byWaguespack et al., fractures of the pelvis, hip, and femurbeing most the common (84%) [21]. Clinical manifestationswere experienced in 81% of the patients with ADO type IIas reported by Benichou et al. and fractures of femur andribs being the most common (76%) [16]. El-Tawil and Stokerreported a fracture rate of 62% (femur most common) [24].67% fractures most commonly in the appendicular skeletonwas reported by Bollerslev and Andersen Jr. [25]. In ourcase, the patient reported mild pain in the lower back regionwhich was radiating to both the lower limbs, but there wasno history of fractures reported in any of the bones, and fullbody radiographic survey of our patient showed no evidenceof fracture in any of the other bones.

Visual impairment and central nervous system involve-ment is rare in autosomal dominant osteopetrosis type II[12]. Severe visual loss was reported in 19% of the patients byWaguespack et al. [21]. Benichou et al. reported visual loss in5% of the patients [16].There were no signs of visual loss andcentral nervous system involvement in our case.

Osteomyelitis is the common clinical manifestation inpatients with autosomal dominant osteopetrosis type II.Waguespack et al. reported osteomyelitis of the femur in 2

Réf . 5

http://ijars.jcdr.net Shingade Raman G. et al., Osteopetrosis with Typical Radiological Findings: Rare Case Report

International Journal of Anatomy, Radiology and Surgery, 2015 Oct, Vol 4(4) 36-38 37

Keywords: Bone, Paediatric, Sclerosing dysplasia

dense but are actually brittle and are susceptible to frequent pathological fractures [1].

Osteopetrosis is a rare bone disorder characterized by defective osteoclastic resorption of primary spongiosa of the bone result in dense sclerotic bone. Persistence of this primitive tissue, interferes with the formation of mature adult bone with a normal medullary canal, which results in abnormally dense but brittle bones. A balance between osteoblastic bone formation and osteoclastic bone resorption is essential for the normal bone growth which is altered in osteopetrosis. The pathogenesis of osteopetrosis is mediated by abnormal osteoclast function. It can be caused due to interference with the acidification of the osteoclast resorption pit, which may occur due to deficiency of the carbonic anhydrase enzyme

encoded by CA2 gene [2]. This enzyme is crucial in proton generation in mature osteoclasts, deficiency of which inhibits the hydrogen ion pumping ultimately resulting in failure to acidify the osteoclast resorption pit [2].

Despite the failure of bone resorption, bone formation continues, resulting in formation of excessive bone. Due to abundance of primitive calcified cartilage, a medullary space is never allowed to form, which leads to anaemia and extramedullary haematopoiesis, causing hepatosplenomegaly. At least four forms of the disease have been identified: (a) an autosomal dominant benign heterogeneous form, (b) an autosomal recessive severe malignant form, (c) an intermediate form that is recessive type, and (d) a recessive type with renal tubular acidosis (also known as carbonic anhydrase II deficiency syndrome)[3-7]. The severe malignant form may be seen in the child born of consanguineous marriage. A study has classified the various metabolic bone diseases according to the component of the affected bone matrix. Osteopetrosis is included in those caused by low bone remodelling along with pyknodysostosis [8].

Radiological findings are classical and include generalized sclerosis of the skeleton with homogeneously increased density of all the bones with little or no differentiation between cortical and medullary regions. While the bones may appear radiopaque, they are actually brittle and subject to pathological fractures, which are characteristically transverse. Multiple striations producing a bone within a bone appearance may be noted. These are called endobones, which represent fetal vestiges [9]. The skull shows basilar and calvarial thickening with increased density, and poorly developed sinuses. Prognathism may be noted if mandible is involved. Failure of bone remodelling leads to flaring and elongation of the metaphyses of the long bones. There may be vertical or horizontal striations of normal bone interspersed with the

[Table/Fig-3a & b] : (a) X-ray both knees AP view shows flaring and elongation of the distal femoral and proximal tibial metaphyses (Erlenmeyer flask type deformity), with uniformly increased density of the bone along with obliteration of medullary cavity. Multiple alternating dense and radiolucent transverse lines in the metaphyses can also be noted (b) Similar radiographic features can be noted in X-ray right wrist with forearm, which additionally shows old healed fracture of mid shaft of right ulna

[Table/Fig-1a & b]: X- ray skull AP and lateral views reveal calvarial and basilar thickening and sclerosis, with poorly developed sinuses and mastoid process. Mild sclerosis of the nasal bone can be noted

[Table/Fig-2a-c]: (a) Chest X-ray demonstrates sclerotic ribs and clavicles with homogeneously increased density and no trabeculations or cortico-medullary differentiation (b) X-ray pelvis with both hips reveals a curved line paralleling each iliac crest (arrows) giving a bone within a bone appearance (c) X-ray DL (dorso-lumbar) spine lateral view shows dense sclerotic bands adjacent to the vertebral endplates with normal mid body, giving the appearance of the “sandwich vertebrae”

Réf . 6

• Fréquence 1 / 250,000

• Peut mener à des décès in utero ou peu aprèsüFractures multiplesüRetard de croissanceüEntrapement des nerfs crâniens: nystagmus, strabisme…üHypercalcémieüPancytopénie – secondaire à l’insuffisance médullaire -,

avec risque de leucémie aigue üHépatosplénomégalie (hématopoïèse extra médullaire)üHémorragie: thrombopénieüCaries dentaires

Ostéopétrose maligne de l’enfantForme autosomale récessive

Pronostic + Traitement

Traitement:• Pour la forme adulte: pas de traitement

• Pour la forme infantile: Greffe de moelle osseuse.

Pronostic: • Pour la forme adulte: bénigne, espérance de

vie normale

• Pour la forme infantile: pronostic sombre avec décès dans l’enfance (avant 10 ans)

• Décès secondaire aux infections, hémorragies et transformation leucémique.

• Quelques rares enfants vivent jusqu’à l’âge adulte moyen.

Références1.Ihde LL, Forrester DM, Gottsegen CJ, et al. Sclerosing bone

dysplasia: Review and differentiation from other causes of osteosclerosis. Radiographics 31:1865–1882. 2011.

2.Florido Angulo A, Holgado Perez S, Perez Andres R. The Sandwich Vertebral Body Sign in Osteopetrosis. Arthritis and Rheumatology 67:1686. 2016.

3. Fotiadou A, Arvaniti M, Kiriakou V, Tsitouridis I. Type II autosomal dominant osteopetrosis: radiological features in two families containing five members with asymptomatic and uncomplicated disease. Skeletal Radiology 38(10):1015-21. 2009.

4.Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med 351:2839-2849. 2004.

5.Kant P, Sharda N, Bhowate RR. Clinical and Radiological Findings of Autosomal Dominant Osteopetrosis Type II: A Case Report. Case Reports in Dentistry article ID 707343. 2013

6.Raman Gangadhar S, Pokhraj Prakashchandra S, Rupal P. Osteopetrosis with Typical Radiological Findings: a Rare Case Report. Int J Anat Radiol Surtg 4:36-38. 2015.

7.www.statdx.com