Back
ditki Logo
medical & biological sciences
All Access Pass - 1 FREE Month!
Institutional email required, no credit card necessary.
Skeletal Dysplasias (eg, Achondroplasia)
Osteogenesis imperfecta Osteopetrosis Osteopoikilosis Ehlers-Danlos Cleidocranial dysplasia Neurofibromatosis Storage Disorders: Gaucher Disease and the Mucopolysaccharidoses
Free One-Month! Institutional (.edu or .org) email required
Log in or start your One-Week Free Trial!

Skeletal Dysplasias (eg, Achondroplasia)

the skeletal dysplasias
Achondroplasia
  • This is an ossification anomaly that manifests with short limbs.
  • Patients have short stature, pronounced lordosis, and bowed legs.
  • This is a more severe form of hypochondroplasia.
Systemic complications
  • Obstructive sleep apnea (OSA)
  • Recurrent otitis media
Neurologic manifestations
  • Macrocephaly
  • Spinal stenosis
  • Hydrocephalus
Genetics
  • Autosomal Dominant (80%) of patients have denovo mutations
  • FGRFR3 gene Mutation
Achondrogenesis
  • Think Achondroplasia but as a Lethal Skeletal Dysplasia -- prenatally morbid or stillbirth.
Marfan syndrome
  • Patients have abnormally long bones.
Systemic complications
  • Dislocated lens (ectopia lentis)
  • Aortic aneurysm and dissection
  • Mitral valve prolapse
  • Long, narrow face, with crowded teeth
  • Scoliosis or kyphosis
Neurologic manifestations
  • Dural ectasia
  • Spinal stenosis
  • Hydrocephalus
Genetics
  • Autosomal Dominant
  • FBN1 gene
  • Fibrillin-1 protein with mycrofibril abnormalities with decreased elasticity
hereditary multiple osteochondromas (aka hereditary multiple exostoses)
  • Bone tumors (osteochondromas) form at the end of long bones and cause shortening of growth.
Systemic complications
  • Transformation from benign tumor to malignancy (sarcoma)
Neurologic manifestations
  • Direct nerve pressure
Genetics
  • EXT1 and EXT2 gene
  • Heparan sulfate is nonfunctional
  • Autosomal Dominant
enchondromatosis (aka Ollier's Syndrome)
  • Bone tumors form at the ends of long bones, near the growth plates, thus these patients generally have short stature.
Systemic complications
  • Transformation from benign tumor to malignancy (chondrosarcoma)
Genetics
  • Somatic (non-heritable)
  • IDH1 & IDH2 genes for isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2
polyostotic fibrous dysplasia
  • Fibrous scar tissue develops in bones.
Mccune-Albright Syndrome
A genetic disorder that occurs in females, involves of polyostotic fibrous dysplasia and also multiple endocrinopathies that notably manifest with precocious puberty and café-au-lait spots.
Endocrinopathies in Mccune-Albright Syndrome
  • Precocious Puberty
  • Hyperthyroidism
  • Goiter
  • Acromegaly
  • Cushing's syndrome (rare)
Dermatologic Manifestations
  • Café-au-lait spots
Genetics
  • GNAS gene for guanine nucleotide-binding protein (G-protein)
fibrous dysplasia ossificans (aka progressive myositis ossificans)
Musculoskeletal structures (muscles, tendons, ligaments) are replaced with bone (ossified). This extra-skeletal ossification causes immobility, manifesting with difficulty even opening one's mouth to eat or ability to breath.
Genetics
  • AVCR1 gene for BMP type 1 receptor
  • Autosomal Dominant
hereditary hypophosphatemic rickets
  • Patients suffer from a bowing of bones due to chronic hypophosphatemia (in adults, this causes osteomalacia – bone softening).
Pathophysiology
  • Hypophosphatemia
Genetics
  • PHEX gene
  • Most common: X-linked dominant
osteopetrosis
  • Bones are abnormally dense (thick).
Systemic complications
  • Anemia
  • Hepatosplenomegaly
  • Immunodeficiency
Neurologic manifestations
  • Cranial neuropathies
osteopoikilosis
  • Bones are spotted with round areas of increased bone density.
osteogenesis imperfecta
  • Bones are abnormally fragile: fractures occur commonly.
  • Mild forms of the disease are associated with blue-appearing sclera.
  • Severe forms are lethal just after birth due to inability to adequately breathe.
Genetics
  • COL1A1 and COL1A2 genes (mostly)
  • Autosomal Dominant (mostly)
Ehlers-Danlos
  • Causes hypermobile joints.
Systemic complications
  • Hypermobile joints
  • Elastic skin
  • Kyphoscoliosis
  • Respiratory changes from severe scoliotic abnormalities
Genetics
  • Autosomal recessive
cleidocranial dysplasia
  • Manifests with abnormalities in the clavicles and skull [delayed closure of the fontanelles], most notably (hence its name).
  • These bones develop from intramembranous ossification, thus we can remember the disorder as one of pathologic intramembranous ossification.
Bony abnormalities
  • Clavicles
  • Skull
  • Teeth
Genetics
  • RUNX2 gene
  • Autosomal Dominant
Additional notable causes of skeletal dysplasia include:
Neurofibromatosis
Storage Disorders: Gaucher Disease and the Mucopolysaccharidoses.
limb and digit development
  • The upper limb bud forms at ~ day 24, followed shortly thereafter by the lower limb bud (at ~ day 28).
  • The limb bud comprises a core of mesenchyme, surrounded by ectoderm.
  • The AER (apical ectodermal ridge) forms a thickening at the distal end of the limb bud.
  • The distal upper limb bud forms a digital plate, distally (for the fingers) and a carpal plate (for the hand). Then, via programmed cell death, digital rays form.

Related Tutorials