Bone and Soft-Tissue Disorders
= PSATHYROSIS = FRAGILITAS OSSIUM = BRITTLE BONE DISEASE = LOBSTEIN DISEASE
= heterogeneous group of a rare generalized connective tissue disorder leading to micromelic dwarfism characterized by bone fragility, blue sclerae, and dentinogenesis imperfecta
Incidence: 1÷15,000 live births per year; M÷F = 1÷1
Genetics: in 80% mutation of COL1A1 gene on chromosome 17 and COL1A2 gene on chromosome 7 that encode type I collagen
Pathophysiology: decreased / defective synthesis of type I collagen → immature collagen matrix → increased bone fragility
- hyperlaxity of joints; blue sclerae; otosclerosis; thin loose skin
- Cranium
- soft skull (caput membranaceum)
- triangular shape of face + frontal bossing
- poor dentition
- malocclusion (← mandibular malformation)
- multiple Wormian bones may persist into adulthood
- retarded calvarial bone formation = abnormally thick / thin calvaria
- brachycephaly = premature fusion of coronal suture → restricted anteroposterior skull growth → compensatory overgrowth of sagittal suture laterally + lambdoid sutures caudally
- frontal fontanel is wider and remains open longer than normal
- sinus + mastoid cell enlargement
- mandibular prognathism ← vertical underdevelopment of dentoalveolar structures + condylar process
- Ear
- otosclerosis = otospongiosis (= thickened undermineralized otic capsule ← markedly delayed + deficient ossification of all 3 layers)
- microfractures + deformities of middle ear ossicles (crus of stapes + handle of malleolus)
- Brain
- generalized cerebral atrophy ← ? impaired outflow of CSF
- hydrocephalus
- widened basilar cistern
Cx: intracranial hemorrhage ← moyamoya disease / vertebral artery damage / vascular fragility / spontaneous intracranial hypotension / friction between multiple bone fragments of skull
- Craniocervical junction
- platybasia
- basilar impression
- basilar invagination
- Spine
- diffuse osteopenia
- defective cortical bone formation
- sclerosis of vertebral endplates
- biconcave vertebral bodies + Schmorl nodes
- collapsed vertebral bodies:
- severe kyphoscoliosis
- platyspondyly = loss of vertebral body height
- biconvex / ellipsoid intervertebral disk spaces of increased height
- spondylolisthesis (5%)
- Thorax
- rib thinning / notching / fractures
- Tubular bones
- generalized osteoporosis = diffuse demineralization, deficient trabecular structure, cortical thinning
- defective cortical bone: increase in diameter of proximal ends of humeri + femora; slender fragile bone; multiple cystlike areas
- multiple fractures + pseudarthrosis with bowing deformity
- normal / exuberant callus formation
- bowing deformities after child begins to walk
OB-US:
- fetal movement may be reduced
- weight of US probe may deform head quite easily
Rx: IV pamidronate administered once every 4–6 months for several years → reduced incidence of fractures and increased bone density, vertebral body height, and cortical bone thickness.
Cx:
- Impaired hearing / deafness from otosclerosis (20–60%)
- Death from intracranial hemorrhage ← abnormal platelet function
Dx: chorionic villous sampling
Classification of Osteogenesis Imperfecta (Sillence, 1979) based on overlapping clinical + radiologic manifestations
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Osteogenesis Imperfecta Type I
= OSTEOGENESIS IMPERFECTA TARDA
◊Most common form of nondeforming mild disease
Transmission: autosomal dominant with varying expression; compatible with life
Prevalence: 3-4÷100,000 live births
Age at presentation: 2–6 years
- blue sclerae (50%); presenile hearing loss (50%)
- normal / abnormal dentinogenesis
- infants of normal weight + length
- osteoporosis; bone density may be normal in adults
- fractures in neonate (occurring during delivery)
- Fractures rare after puberty as ossification is complete!
OB-US:
- marked bowing of long bones
- NO IUGR
Osteogenesis Imperfecta Type II
= CONGENITAL LETHAL OSTEOGENESIS IMPERFECTA
= least common perinatal (obstetrical) lethal form
Transmission: sporadic new dominant mutations / autosomal recessive
Prevalence: 1÷54,000 births
- disease manifest at birth (in utero); NO hearing loss
- blue sclerae; ligamentous laxity + loose skin
- shortened broad crumpled long bones
- bone angulations, bowing, demineralization
- localized bone thickening from callus formation
- thin beaded ribs ± fractures → bell-shaped / narrow chest
- thin poorly ossified skull
- wormian bones (present in most cases)
- spinal osteopenia
- platyspondyly
OB-US:
- A normal sonogram after 17 weeks MA excludes the diagnosis!
- increased through-transmission of skull ← extremely poor mineralization:
- unusually good visualization of brain surface + orbits
- increased visualization of intracranial arterial pulsations
- abnormal compressibility of skull vault with transducer
- decreased visualization of skeleton
- multiple fetal fractures + deformities of long bones + ribs:
- wrinkled appearance of bone ← more than one fracture in single bone
- beaded ribs ← callus formation around fractures
- abnormally short limbs
- small thorax ← collapse of chest cage
- decreased fetal movement
- infants small for gestational age (frequent)
- polyhydramnios + nonimmune hydrops
Prognosis: stillborn / death shortly after birth ← pulmonary hypoplasia / cerebral hemorrhage
DDx: congenital hypophosphatasia; achondrogenesis type I; camptomelic dysplasia
Osteogenesis Imperfecta Type III
= SEVERE PROGRESSIVELY DEFORMING OI
Transmission: autosomal recessive; progressively deforming disorder compatible with life
Prevalence: 1-2÷100,000 live births
- bluish sclerae during infancy that turn pale with time
- joint hyperlaxity (50%); small nose, soft skull
- NO hearing loss
- micrognathia
- decreased ossification of skull
- normal vertebrae + pelvis
- shortened + bowed long bones
- progressive deformities of limbs + spine into adulthood
- ± rib fractures
- multiple fractures present at birth in ⅔ of cases
- fractures heal well
OB-US:
- short + bowed long bones
- fractures
- humerus almost normal in shape
- normal thoracic circumference
Prognosis: progressive limb + spine deformities during childhood / adolescence
Osteogenesis Imperfecta Type IV
= less severely deforming than type III
Transmission: autosomal dominant
Prevalence: 3-4÷100,000 live births
- normal scleral color; hearing loss
- tubular bones of normal length; mild femoral bowing may occur
- osteoporosis
OB-US:
- bowing of long bones