Skeletal Dysplasias

Dysostoses are developmental anomalies from abnormal migration, usually limited to defined embryological structures. Dysplasias are from mutations in regulators of skeletal organogeneses (eg signaling molecules), or matrix components.


Uncommon congenital malformations, usually failure of a bone to develop (eg phalanx, rib, clavicle), formation of extra bones (eg supernumery ribs or digits), fusion of digits (syndactyly), or long spider digits. Usually from alterations in transcription factors esp homeobox genes.

  • Cleidocranial dysostosis (cleidocranial dysplasia, pelvicocleidocranial dysplasia) – Abnormal development of membranous bones, autosomal dominant, 1/3 spontaneous. Small face with wide head and hypertelorism, delayed closure‘of sutures (eg persistent metopic suture) and fontanelles, wormian bones, supernumery teeth. Hypoplastic/absent clavicle (usually middle/lateral). Coxa vara, wide symphysis pubis.
  • Synpolydactyly – Extra digit with fusion.
  • Waardenbury syndrome – Hearing loss, abnormal pigmentation, craniofacial abnormalities.
  • Greig syndrome – Synpolydactyly, craniofacial abnormalities.
  • Campomelic dysplasia
  • Oligodontia – Absence of teeth.
  • Nail-patella syndrome (osteo-onychodysostosis, Fong syndrome) – Rare, AD. Posterior iliac horns (pathognomonic), absent/hypoplastic patellae, hypoplastic lateral femoral condyles, genu valgum, hypoplastic capitellum, radial head dislocation, short 5th MC, dysplastic fingernails (esp thumb, index fingers), clinodactyly, progressive nephropathy.
  • Holt-Oram syndrome – Forelimb anomalies esp carpal bones, thumb, radial ray aplasia/hypoplasia. Associated with cardiac anomales esp ASD, VSD.
  • Ulnar-mammary syndrome – Hypoplastic/absent ulna, 3rd-5th digits, breast and teeth, delayed puberty.


Most from defects in hormones and signal transduction mechanisms. Source of defects include cartilage (chondro-), bone (osteo-), vertebrae (spondylo-), formation (-plasia) and growth (-trophy). Skeletal dysplasia with disproportionate limb or spinal shortening. Limb shortening classified as rhizomelic (root/proximal ie humerus and femur), mesomelic (middle ie radius-ulna and tibia-fibula; rare), acromelic (end/distal), or micromelic (entire limbs). Need to know other bone involvement (skull, spine, thorax, pelvis), epiphyseal/metaphyseal/diaphyseal, narrow/wide bones. Other features to note include epiphyseal fragmentation (small punctate or irregular ossicles), abnormal acetabulum (horizontal or near horizontal roof, trident acetabulum), skull enlargement, short ribs, short spine, abnormal vertebral bodies, abnormal iliac wings (short, tall or squared). Trident acetabulum – 3 inferior-pointing spikes (upside-down trident), seen in Jeune syndrome, Ellis-van Creveld syndrome, thanatrophoric dysplasia. Screening radiographs should include lateral skull, AP and lateral T/L spine, chest including shoulders, AP pelvis/hips, AP single upper and lower extermity, PA hand.

Achondroplasia and mimics:

  • Achondroplasia – Most common (1:26,000), autosomal dominant (homozygous lethal), 80% spontaneous (almost all in paternal allele), mutation causing activition of FGF receptor 3 (FGFR3) which inhibits cartilage proliferation. Normal IQ and life expectancy. Rhizomelic with metaphyseal flaring. Relatively normal trunk length. Enlarged skull with protuberant forehead and depression at the root of nose and short skull base, small foramen magnum and jugular foramina (may -> brainstem compression). Narrow interpedicular distance reducing inferiorly (prone to spinal stenosis), short pedicles, lumbar kyphosis being bullet-shaped in infancy then mildly flattened, posterior vertebral body scalloping, enlarged disk spaces. Short ribs. Tombstone iliac bones (squared iliac wings), champagne glass narrow pelvic inlet, horizontal acetabulum. Trident hands with space between middle fingers and equal length of 2nd-4th fingers. Main morbidity is from spinal and cranial stenosis.
  • Hypochondroplasia – Defect in type 2 collagen. Similar to achondroplasia except skull and pelvis relatively spared.
  • Pseudoachondroplasia – AD, usualy not detected until 10s-30s. Short limbs and trunk, short hands and feet, normal face and skull. Vertebral bodies may be flattened with anterior beaking or be normal. Ribs broad and flat (like spatula). Acetabular roof irregular and horizontal. Fragmented deformed epiphyses, widened metaphysis. Proximal MC rounding, hypoplastic carpals and tarsals.

Lethal dwarfisms:

  • Thanatophoric dysplasia – Fatal, activation of FGFR3. Severe micromelic, cloverleaf skull (global synostosis) with macrocephaly and frontal bossing, short ribs with hypoplastic chest, bell-shaped abdomen, platyspondyly with U-shaped bodies and narrow interpedicular distance, widened disk spaces, squared iliac wings with horizontal acetabula, meataphyseal flaring, telephone-receiver femurs (short and curved).
  • Achondrogenesis – AR, both fatal but type I more severe than II, defect in type 2 collagen. Extremely micromelic, large head, no/minimally ossified vertebral bodies, short ribs ± fractures, poorly ossified pelvis.

Very short ribs:

  • Asphyxiating thoracic dysplasia (Jeune syndrome) – AR. Very short ribs with bulbous ends, pulmonary hypoplasia, clavicles project far superior to ribs. Trident pelvis (spur-like triradiate cartilage), may have ossification of capital femoral epiphysis. Acromelic (short middle and distal phalanges with cone-shaped epiphyses), metaphyseal irregularity and beaking. If survives respiratory compromise then bone abnormalities improve but progressive renal disease.
  • Chondroectodermal dysplasia (Ellis-van Creveld syndrome) – AR, Armish community. Associated with sparse hair, abnormal nails and teeth congenital heart disease. Short ribs with long narrow thorax. Trident pelvis, hypoplastic iliac wings, capital femoral epiphyses ossified. Acromelic, wide irregular metaphysis (esp distal ulna and radius), polydactyly (ulnar-side), hamate and capitate fusion.
  • Camptomelic dysplasia (‘bent limb’) – Associated with ambiguous genitalia or female XY, cleft palate. Poorly ossified posterior elements C/T-spine, small thorax with 11 rib pairs, hypoplastic scapula. Poorly ossified pelvis with tall narrow iliac wings. Micromelic, anterior and lateral bowing of long bones in lower limbs.
  • Metatrophic dysplasia (‘changing’) – Rare. Tail-like appendage or skin fold over sacrococcygeal region. Develops platyspondyly and kyphoscoliosis after birth, C1-2 instability from dens hypoplasia. Short ribs. Horizontal acetabular roofs. With growth short limbs grow while spine shortens. Wide club-shaped metaphyses.


  • Chondrodysplasia punctata – AD (Conradi’s disease) or AR. Rhizomelic, stippled epiphyses, coronal vertebral body clefts. Cataracts.
  • Pyknodysostosis
  • Diastrophic dysplasia (‘twisted’) – AR . Narrowing lumbar interpedicular distance, scoliosis, cervical kyphosis, posterior scalloping. Rhizomelic, metaphyseal enlargement, stippled or crescent-shaped epiphyses, Hitchhiker thumb (short 1st MC), clubfeet. Enlarged earlobes.
  • Mesomelic dysplasias – Group of mesomelic dwarfisms, mandibular hypoplasia. Dyschondrosteosis (Leri-Weill disease) is AD presenting late childhood with Madelung deformity (volar-ulnar distal radial physeal abnormaityl causing tilt in that direction, wide DRUJ, reduced ROM; DDx Turner).

Spondyloepithelial Displasias (SED)

  • Spondyloepiphyseal dysplasia congenital (SEDC) – AD. Short spine with ovoid/pear shaped bodies (later platyspondyly), dens hypoplasia (C1-2 instability), scoliosis. Flat face ± cleft palate. Pectus carinatum. Irregular fragmented epiphyses with delayed ossification.
  • Spondyloepiphyseal dysplasia tarda (SED-tarda) – X-linked recessive presenting in adolescence with back/hip pain, reudced ROM, short spine. Platyspondyly, anterior disk space widening and posterior space narrowing. Small irregular epiphyses, early OA.

Collagen Defects

Includes OI, achondrogenesis, hypochondrogenesis, Sticlker syndrome, MED, MChD.

Osteogenesis Imperfecta (OI)

(Type 1 collagen disease, brittle bone disease). Abnormal type 1 collagen with osteopenia and propensity for fracture (DDx child abuse, Caffey’s disaese, Menkes syndrome). Most autosomal dominant. Multiple fractures of various ages. Multiple wormian bones (>12 ossicles along cranial sutures), blue sclera (in 90%), thin skin, hearing loss (otic bone fractures), grey teeth (dentinogenesis imperfecta). May cause platybasia with basilar invagination.

  • Type I (most common) – AD, mild weak bones, normal/short stature. Ia no dentinogenesis imperfecta, Ib present.
  • Type II – AD/AR, most severe, fatal in neonatal period with rib fractures causing pulmonary hypoplasia and infections. Bones may be broad, crumpled like accordian or thin and long with multiple fractures.
  • Type III – AD/AR, severe weak bones, very short stature.
  • Type IV -AD, mild to severe weak bones, short stature. IVa no dentinogenesis imperfecta, IVb present.

Multiple Epiphyseal Dysplasia (MED)

(Fairbank disease). AD, defect in type 9 collagen. Presenting late childhood/adolescence with joint pain/limb, mildly short limbs. Defective secondary growth centres esp tubular bones, wrists and ankles with delayed ossification, small and fragmented epiphyses. Schmorls nodes and mild vertebral flattening. Coxa vara. Early OA.

Metaphyseal Chondrodysplasia (MChD)

Group of dysplasias with metaphyseal deformity, short stature. Defect in type 10 collagen.

  • Schmid type – Most common, AD. Bowed legs, metaphyseal flaring, widened irregular physes, cupped anterior rib ends. DDx rickets but normal zone of provisional calcification.
  • McKusick type (cartilage hair syndrome) – AR, Armish community. More severe metaphyseal flaring, cone-shaped epiphyses. Sparse hair.
  • Shwachman-Diamond syndrome – AR. Metaphyseal dysplasia with exocrine pancreatic insufficiency and phymphocyte dysfunction.
  • Jansen type – Rare, very short stature.

Stickler Syndrome

AD defect in collagen type II or XI. Underdeveloped midface with flattening, U/V-shaped cleft palate, Pierre Robin sequence (micrognathia, glossoptosis, upper airway obstruction), hearing loss, joint hypermobility, precocious OA, early cataract, myopia.

Mucopolysaccharidoses (MPS)

Inborn errors of mucopolysaccharide metabolism causing accumulation in bone marrow, brain, liver, other organs and excretion in urine. Cartilage formation is severely affected. Skeletal findings are similar, being dysostosis multiplex. Short stature from platyspondyly or oval vertebral bodies, anterior beak (mid vetebral body in Morquio, inferior in Hunter/Hurler) most prominent in lumbar spine, focal thoracolumbar kyphosis (gibbus deformity from small or retrolisthesed ~L1). Thickened clavicles and ribs with narrowing posteromedially (canoe paddle/oar-shaped). Flared iliac wings (similar to achondroplasia) with shallow acetabuli. Dysplastic femoral heads, femoral necks gracile/broad and coxa valga. Short long bones with wide metaphyses and diaphyses. Squared metacarpals with tapered/pointed proximal ends (fan-like appearance) and notched ulnar aspect (esp 5th metacarpal base). Flattening of nasal bones. Osteopenia with coarse trabuculae. J-shaped sella turcica.

  • Hurler syndrome – Early severe dysostosis multiplex.
  • Morquio syndrome – No mental retardation (cf others). Added dens hypoplasia with C2 expansion and displacement of posterior arch C1 into foramen magnum. May develop platyspondyly. Delayed ossification of epiphyses with fragmentation.
  • Hunter syndrome

Other storage diseases may also cause dysostosis multiplex (eg mucolipidoses, Gaucher disease) but take years to develop as metabolites accumulate.

Sclerosing Bone Dysplasias

Dense bones, most from failed osteoclasts. Mixing sclerosing bone dysplasia – simultaneous melorheostosis, osteopathia striata and/or osteopoikilosis.

Acquired diseases include:

  • Renal osteodystrophy
  • Myelofibrosis
  • Hypothyroidism
  • Chronic infection (including TORCH esp rubella, syphyllis)
  • Heavy metal poisoning

Caffey Disease

(Infantile cortical hyperostosis). Self-limiting disease of infants with exuberant periosteal new bone. Esp mandible, ulna, clavicle. Usually presents <6/12.


(Marble bone disease, Albers-Schönberg disease). Rare, osteoclasts defective in resorbing and remodeling bone -> very dense brittle bones (like chalk). Osteoclasts may have periods of more normal function causing dense metaphyseal bands, bone-within-bone appearance (DDx normal periods of rapid growth). Undertubulation with wide metaphyses (Erlenmeyer flask deformity). Sandwich vertebra – dense endplates with prominent posterior vascular notches. Thickened skull base encroaching on cranial nerves -> blindness, hearing loss. Dental dysplasia and infections. Serum calcium paradoxically low, may have superimposed rickets. Lack of marrow space -> pancytopaenia, often -> complications and death.

  • Infantile/precocious form – Absent corticomedullary differentiation (ie no medullary space), hepatosplenomegaly, fatal neonatal pancytopenia.
  • Delayed/adult type – Fracture in later life, mild anaemia, markedly thickened cortices.
  • Intermediate autosomal recessive type (rare) – Findings between infantile and delayed types.
  • Osteopetrosis associated with renal tubular acidosis – Cerebral calcifications, mental retardation, skeletal abnormal improve during life.


Rare, AR. ?Type of osteopetrosis. Dwarfism, diffuse osteosclerosis, transvere fractures, wormian bones, preservation of anterior fontanelle as adult, progressive resorption and fragmentation of distal phalanges ± distal clavicles.

Progressive Diaphyseal Dysplasia

(Diaphyseal dysplasia Englemann type, Camurati-Englemann disease). AD. Symetric endosteal and periosteal thickening, expansion of diaphyses (esp legs). Epiphyses spared.

Ribbing Disease II

(Hereditary multiple diaphyseal sclerosis). ?Variant of progressive diaphyseal dysplasia, similar findings except asymmetric and less widely distributed, later presentation.


Benign, familial. Multiple enostoses clustered around joints including epiphyses (cf blastic metastases tend to spare epiphyses). Occasional subcutaneous fibrous nodules/plaques. Rarely reduced joint ROM, contractures.

Osteopathia Strata

(Voorhoeve’s disease). Benign. Uniform dense metaphyseal longitudinal bands. In ilium radiate from acetabulum in sunburst pattern.


Dense bone along cortex (usually periosteal, may be endosteal) of otherwise normal bone in irregular wavy pattern (dripping candle wax). Usually single extremity in portion of skeleton innervated by a spinal nerve (sclerotome). Pain, contractures, overlying erythema/shiny skin, reduced ROM, premature physeal closure. Normal life expectancy.

Multiple Hereditary Exostoses (MHE)

(Osteochondromatosis, diaphyseal aclasis). Multiple bilateral osteochondromas, bony growths from metaphysis continuous with bony cortex, tend to point away from joints, esp knee. May -> limb shortening, leg length discrepancy, bowing, deformity, compression of nerves/vessels, malignant degeneration -> chondrosarcoma (5%, esp proximal lesions).


(Ollier disease). Multiple enchondromas, commonly bilateral, esp hands and feet. Metaphyses of long bones, oblong/flame-shaped/linear perpendicular to physis. Malignant degeneration in 30%.

Maffucci syndrome – Enchondromatosis in association with soft tissue venous malformations. Phleboliths. Higher risk of malignant degeneration as well as malignancy in abdomen, CNS.

Metachondromatosis – Rare combination of Ollier disease and diaphyseal aclasis.

Trevor Disease

(Fairbank’s disease). Rare, asymmetrical limb deformity due to localised overgrowth of cartilage resembling osteochondroma in an epiphysis. ?Defect in limb bud in early foetal life. Mostly ankle or knee, always confined to a single limb.