skeletal dysplasia-1.pptx presentation for students

Skeletal dysplasia

1. Skeletal Dysplasia dr DR.JYOTI

2. Heterogeneous group of over 400 disorders. Incidence of 1/5000; The disorders in the same family share a common genetic abnormality as well as a core radiologic pattern with minor differences between individual disorders. Learning Objectives 9

3. Skeletal Dysplasia Families: Dysostosis multiplex family (mucopolysaccharidosis [MPS], mucolipidosis, and oligosaccharidosis) Achondroplasia family - thantophoric,achondroplasia,hypochondroplasia Multiple epiphyseal dysplasia (COMP) family Skeletal ribosomopathies (metaphyseal dysplasias) Type II collagenopathies – SEDC group and Stickler- Kniest group Metatropic dysplasia (TRPV4) family Diastrophic dysplasia (DTDST) family Larsen dysplasia family ( filaminopathy B ) 9.Skeletal ciliopathies 10. Punctata family Osteogenesis imperfecta group Osteopetrosis group – osteopoikilosis,osteopathia striata,melorrheostosis

4. Step wise approach to diagnose skeletal dysplasias Step 1 : Recognition of the overall pattern (or pathognomonic finding) to categorize a case into a specific skeletal dysplasia family. Step 2 : Examine further details to reach the diagnosis Here’s the key! Skeletal Dysplasia Families and Pattern Recognition Example # Step 1 : The overall pattern matches dysostosis multiplex ( f lared ilia and wine glass appearance, proximal metacarpal tapering, hooked vertebrae) Step 2 : The presence of platyspondyly (flat spine), in addition to above findings , suggest s Morquio disease, which can be confirmed with urine test

5. Dysostosis multiplex family : a heterogeneous group of lysosome storage diseases Hurler, Hunter, and Morquio syndromes (different types of MPS ) share common skeletal changes termed dysostosis multiplex — eg, flared ilia, a wineglass appearance of the inner pelvic rim , constriction of the proximal fem urs with coxa valga , hooked vertebral bodies , proximal metacarpal pointing, and bullet- shaped phalanges . Morquio syndrome uniquely show s platyspondyly (flat vertebral bodies) and prominent epiphyseal dysplasia . Constriction of the proximal femora with coxa valga Proximal metacarpal pointing and bullet- shaped phalanges Hooked vertebral bodies Flared ilia and wine glass appearance of the inner pelvic rim Constriction of the proximal femora with coxa valga Proximal metacarpal pointing and bullet- shaped phalanges Hooked vertebral bodies Flared ilia and wine glass appearance of the inner pelvic rim Constriction of the proximal femora with coxa valga Proximal metacarpal pointing and bullet- shaped phalanges Hooked vertebral bodies Flared ilia and wine glass appearance of the inner pelvic rim Epiphyseal dysplasia Key images A young child A child Hurler disease (MPS IH) Hunter disease (MPS IIA) Morquio disease (MPS IV) Platyspondyly A young child J shaped sella

6. Thanatophoric dysplasia, achondroplasia, and hypochondroplasia (FGFR3-related bone dysplasias) share common skeletal changes in decreasing order of severity — eg, a narrow thorax , caudally decreased interpediculate distances , vertebral deformity, small iliac bones with short sciatic notches , ovoid lucency in the proximal femora , and short and broad tubular bones with metaphyseal cupping/flaring . Extremely narrow thorax Small iliac bones with trident appearance Posterior bowing of the tibia/fibula Disproportionately large skull “Bullet- shaped” flat vertebral bodies and narrow spinal canal Narrow, bell- shaped thorax Absence of normal increase in caudal interpediculate distances Ovoid lucency in the proximal femora Small iliac bones with short sacrosciatic notches and “trident” acetabula Short long bones with metaphyseal cupping Disproportionately large skull Mildly narrow thorax long bones Absence of normal caudal interpediculate widening Small iliac bones with short sacrosciatic notches Ovoid lucency in the proximal femora Mild shortening with metaphyseal flaring of Thanatophoric dysplasia Decreased caudal interpediculate distances Achondroplasia Family (FGFR3- related bone dysplasias) Milder Severe platyspondyly Milder Ovoid lucency of the A stillbirth proximal femur Severe shortening of long bones with metaphyseal cupping “French telephone receiver femur” (bowed, short femur) A neonate Achondroplasia Hypochondroplasia A neonate “Trident” hand

7. Radiologic approach 1 st step : Common radiologic findings include: Shortening of the skull base Deformity of the vertebral bodies Narrowing of the caudal interpediculate distances Iliac hypoplasia Ovoid radiolucency of the proximal femora Metaphyseal cupping and flaring with metaphyseal spur of tubular bones 2 nd step : The three disorders show different severity and unique findings TD shows thoracic hypoplasia with severely shortened ribs and severe platyspondyly (flattening of vertebral bodies) TD type 1 shows French telephone receiver– like bowing of fem urs ; type 2 show s clover leaf skull deformity and straight fem urs ACH is the prototype of this family; limb shortening and spondylar changes are much milder than those of TD. " Trident” hand HCH show s only narrow interpediculate distance, iliac hypoplasia, and radiolucency of Key images http://www.oldphoneworks.com/ “French telephone receiver femur” TD ACH Thanatophoric dysplasia Achondroplasia Clinical and genetic features Achondroplasia family shows gain- of- function mutations of the FGFR3 gene, including thanatophoric dysplasia (TD), achondroplasia (ACH), and hypochondroplasia (HCH) in decreasing order of severity . FGFs- FGFR3 signaling inhibits proliferation of chondrocytes and synthesis of cartilage matrix . TD, ACH, and HCH have disease- specific FGFR3 mutations; thus, they show a homogeneous skeletal phenotype. Patients with the three disorders manifest with short- limb short stature ; TD is perinatally lethal owing to thoracic hypoplasia as a result of severe rib shortening . t he proximal fe mur Achondroplasia f amily: a group of allelic disorders related to FGFR3 gene

8. Multiple epiphyseal dysplasia family (COMP- related bone dysplasias) Pseudoachondroplasia MED (mild) Shortened short tubular bones with small epiphyses and cupped metaphyses Small epiphyses with cupped metaphyses Small, round capital femoral epiphyses Platyspondyly with biconvex vertebral bodies Small, round capital femoral epiphyses Small, irregular epiphyses with cupped metaphyses Shortened short tubular bones with small epiphyses MED (severe) Mild biconvexity of vertebral bodies Mild biconvexity of vertebral bodies Mildly small epiphyses Milder Pseudoachondroplasia (PsACH) and multiple epiphyseal dysplasia (COMP- related MED) share the same pattern of abnormal epiphyseal ossification — i e, delayed epiphyseal ossification with small, round, irregular epiphyses . However, PsACH (the severest phenotype of this group) shows prominent spondylar dysplasia and metaphyseal dysplasia . A young child Severer A young child A child

9. Metaphyseal dysplasia most conspicuous in the hips Mildly narrow thorax Metaphyseal dysplasia more conspicuous in the knees A 1- year- old A 2- year- old female Brachydactyly with metaphyseal cupping Shwachman- Diamond syndrome Cartilage hair hypoplasia Shwachman - Bodian - Diamond syndrome (SBDS) and cartilage hair hypoplasia (CHH), manifest with metaphyseal dysplasia. Metaphyseal dysplasia of the hip is conspicuous in SBDS, while that of the knee is conspicuous in CHH. A narrow thorax is prominent in SBDS, while brachydactyly is distinctive in CHH . M etaphyseal dysplasias

10. metaphyseal dysplasia = rickets-like metaphyseal changes (splaying, cupping, and irregularity). Contrary to rickets with diffuse osteopenia ( osteomalacia ) (  ), bone mineralization is normal in ribosomopathies ; metaphyseal dysplasia has a postnatal onset.

11. The s pondyloepiphyseal dysplasia congenita ( SEDC) family is a subgroup of of type II collagenopathies that forms a continuous radiographic spectrum and is characterized by delayed ossification of juxta truncal bones ( vertebral bodies , pelvic bones , and epi metaphyses of long bones , especially of the proximal segment) . V ertebral ossification ranges from total absence to modest modification (pear - shaped vertebral bodies); pubic ossification is usually absent, and ischial ossification may be missing . A stillb orn Small ilia with concavities of the inner and inferior margin Severe shortening of long bones with striking metaphyseal cupping Absent ossification of the pubic and ischial bones Small ossification of the vertebral bodies. Ossification of the cervical vertebral bodies and sacrum is absent Moderate shortening of long tubular bones The ilia and ischia are ossified, while the ossification of the pubic bones is absent A stillborn Short and broad ilia with horizontal acetabular roof and absent pubic ossification Long tubular bones show delayed epiphyseal ossification, shortening, and mild metaphyseal broadening Severer Severer Achondrogenesis type 2 Hypochondrogenesis Near ly complete absence of spinal ossification A neonate Spondylar dysplasia with dorsally wedged, pear- shaped vertebral bodies Type II collagenopathies (1) – SEDC family Spondyloepiphyseal dysplasia congenita

12. The other subgroup of type II collagenopathies is Stickler- Kniest dysplasia family, which is radiologically characterized by dumbbell - shaped deformity of long bones and spondylar dysplasia . Kniest dysplasia show s severe dumbbell deformity and platyspondyly with coronal clefts; Stickler dysplasia show s a milder phenotype but is frequently associated with severe micrognathia (Pierre- Robin sequence) . A neonate (Handa et al. Radiographics 2021) Severe metaphyseal broadening of tubular bones (“dumbbell " deformity) Delayed epiphyseal ossification of long bones , Large ossification of the talus and calcaneus Moderate platyspondyly with anterior wedging. Coronal clefts at the thoracolumbar junction Mild platyspondyly Kniest dysplasia Stickler dysplasia Broad and short ilia A neonate (Handa et al. Radiographics 2021) Mild metaphyseal broadening of tubular bones, causing mild “dumbbell " deformity Micrognathia Type II collagenopathies (2) – Stickler- Kniest family Severer

13. Larsen dysplasia family (Filaminopathies B ) : a group of allelic disorders related to abnormal filamin B Larsen dysplasia Larsen dysplasia family (filaminopathy B) is a continuous spectrum of disorders characterized by joint dislocations . Common imaging features include cervical kyphosis , distal humeral tapering , multiple dislocations , and broadening of short tubular bones . Distal humeral tapering Multiple dislocations Broadening of short tubular bones Cervical kyphosis and large odontoid process A neonate

14. Skeletal ciliopathies : a heterogeneous group of skeletal disorders with abnormal primary cilia A neonate Extremely short ribs Mild shortening of long bones with bowing Brachydactyly and post- axial polydactyly Trident - shaped ilia Cone- shaped epiphyses A 3- year- old Jeune asphyxiating thoracic dysplasia Ellis – v an Creveld syndrome Skeletal ciliopathy is a subset of ciliopathy mainly affecting the skeleton; the prototypes are Jeune asphyxiating thoracic dysplasia and Ellis – v an Creveld (EvC) syndrome; both disorders share common radiologic findings such as short ribs , short limbs , brachydactyly (later with cone- shaped epiphyses ) with or without polydactyly, trident pelvis , and premature ossification of the femoral heads .

15. Osteogenesis imperfecta group : a group of disorders related to type I collagen OI (severe, type 3 ) OI (mild, type 1 ) Osteogenesis imperfecta (OI) is a family of disorders characterized by variable degrees of osteoporosis and repeated fractures . Mild OI manifests with multiple w ormian bones and slender bones with fractures and/or bowing. Severe OI manifests as severely defective skull ossification and crumpled- appearing thick bones as a result of in utero fractures/healing. Thick and deformed “accordion- like” long bones due to in utero fractures/healing Multiple rib fractures and vertebral body compression fractures Long bones are mildly slender and bowed with an old fracture in the left distal tibia. Generalized osteoporosis Multiple w ormian bones along the lambdoid sutures A neonate Severer A child

16. Osteopetrosis group : a group of disorders with dense but brittle bones Osteopetrosis (OP) is a heterogeneous group of conditions characterized by generalized bone sclerosis . O P comprises three clinical groups (infantile, intermediate, and late onset ), which are based on the timing of onset. Pyknodysostosis is a special form of OP. Bones are generally sclerotic with poor corticomedullary differentiation Generalized sclerosis Sandwich appearance of the vertebral bodies with fracture Old fractures of the tibiae Acro - osteolysis (pathognomonic) A neonate O P (early onset) O P (late onset) Pyknodysostosis Sclerotic craniofacial bones, particularly the skull base A young adult patient with trauma Widely opened fontanels Severe micrognathia with an obtuse mandibular angle Generalized sclerosis with preserved corticomedullary differentiation An adult patient with trauma Severer

17. Thanatophoric dysplasia.

18. abnormal punctate calcifications ( puncta , stippling) in cartilage—epiphyseal cartilage and juxtacartilaginous soft tissues in particular RHIZOMELIC NON RHIZOMELIC Autosomal recessive ,fatal Autosomal dominant ,non lethal Epiphysis stippling in hips ,shoulders, knees Stippling at end of long bones and short tubular bones Symmetric shortening of limbs Assymetric limb shortening Metaphysis flared,long bones bowed Spine normal Metaphysis ,diaphysis normal Spine-stippled ossification centres Mental retardation Normal intelligence Chondrodysplasia punctata

19. (A ) Frontal radiograph in a neonate with Conradi-Hünermann –type CDP shows multiple puncta of the spine, epiphyses of the long bones, and tarsal bones. Vertebral ossification is defective. The long bones are asymmetrically short. (B) Frontal and lateral radiographs in a neonate with rhizomelic -type CDP show multiple puncta of the pelvic bones, long bone epiphyses, patella, and spine (to a lesser degree). The humeri and femurs are severely short ( rhizomelic shortening). There are multilevel coronal clefts of the vertebral bodies (arrowheads)

20. Broad crumpled long bones Severly demineralised calvaria Beaded fractured ribs