Diastrophic Dwarfism
Inheritance
Unknown pathogenesis
Clinical Features
- Severe dwarfism (rhizomelic, short limbs)
- Often misdiagnosed as achondroplasia
- Associated with scoliosis and kypho-lordosis, equino varus deformities of feet, multiple joint contractures (hip, elbow, knee) and hip dislocation and acetabular dysplasia
- Also associated with spinal stenosis, scoliosis and kyphosis, atlanto-axial instability, cauliflower ears, cleft palate and hitch-hikers thumb
X-Rays
- Short and thick long bones
- Distorted flattened epiphyses, late ossification
- Spina bifida occulta of the cervical spine in almost its entirety
- Cervical kyphosis
Cleidocranial dysplasia
Characterised by deficient or imperfect ossification of bones formed in membrane (clavicles, cranium). Also affects pelvis and bones of hands and feet
Inheritance
Autosomal dominant (1/3 sporadic)
Incidence
- True incidence is unknown
- Usually evident in first 2 years of life
Clinical Features
- Large head, relatively small face, drooping shoulders and& narrow chest
- One or both clavicles may be affected (usually middle or lateral 1/3, rarely the medial 1/3)
- When bilateral can touch shoulders in front
- Frontal, parietal and occipital bossing
- Pelvic involvement almost always symmetrical
- May be muscular deficiencies associated with clavicle defect
- Coxa vara may be a feature
X-Rays
- Ossification of cranial portion of skull, not base affected
- Multiple wormian bones
- Pelvis
- Wide symphysis
- Rami improperly fused
- Widening of SI joint
- Spina bifida occulta in thoracic and lumbar spine
- Ossification of tarsal and carpal bones delayed
- Terminal phalanges hypoplastic
- Extra-epiphysis at proximal ends of 2nd – 5th metacarpals and metatarsals
Pathology
- Unknown exact cause
- Failure of ossification of midline junction of bones
Treatment
- Little if any functional defect
- Coxa vara may require osteotomy, if present
Pyknodysostosis
Inheritance
Autosomal recessive
Clinically
- Short stature
- Skull dysplasia with failed closure of sutures, hyoplastic jaw and Wormian bones
- Hypo / dysplastic clavicles
- Acro-osteolysis of terminal phalanges
- Koilonychia nails and recurrent fractures
Fibrous dysplasia
- A benign fibro-osseous pathologic entity of undetermined aetiology
- Characterised by expanding fibro-osseous tissue in the interior of affected bones
- Predominantly a lesion of the growing skeleton
- Called a dysplasia, because of the observed inherent lack of normal osteoid production, leading to the formation of primitive fibre bone trabeculae
Incidence
- Exact incidence unknown (not rare)
- Male : Female 1:3
- Not hereditary, all reported cases sporadic
Classification
- Monostotic
- Polyostotic
- Associated with endocrine abnormalities
- Albrights disease
- Skin pigmentation
- Polyostotic fibrous dysplasia
- Precocious puberty (usually female)
Clinical Features
- May be asymptomatic and present incidentally or with endocrine dysfunction
- Almost any bone may be affected
- Most common : Femur, tibia, humerus, rib or facial bone
- May have pain and limp, if neck of femur involved
- Polyostotic form is usually more obvious with segmental involvement, leading to pain, LLD, bowing of long bones and other deformities, coxa vara (shepherds crock deformity)
- Pathological fracture not uncommon
- May involve facial bones
- Non skeletal manifestations
- Abnormal cutaneous pigmentation (coast of Maine, irregular outline) evident in ~ 35% of cases (Polyostotic)
- Hyperthyroidism
- Cushings
- Acromegaly
- Hyperparathyroidism
- Hypophosphataemic rickets
- Endocrine dysfunction is almost restricted to females, though a few cases of hyperthyroidism have been seen in males (sexual precocity, diabetes mellitis or hyperthyroidism)
- Sexual precocity seen in ~ 20% of cases. They grow more rapidly, but early fusion of growth plates leads to short stature
X-Rays
- Generally long bone lesions tend to involve the metaphysis and spread towards the diaphysis
- Typical ground glass appearance of lesions
- Cortex may be thinned by endosteal erosions, but there is always a thin shell of cortex, unless fractured
- Multi-locular appearance, but the lesions are unicameral
- In long bones, lesions are usually metaphyseal extending into the diaphysis
- CT demonstrates ground glass appearance of matrix
- Bone scan shows increased uptake
Investigations
- May have an elevated alkaline phosphatase, but not related to extent or activity of disease
- Other biochemical parameters are normal
Pathology
- Exact cause is unknown
- A disorder of postnatal cancellous bone maintenance, where normal bone undergoing physiologic lysis is replaced by an abnormal proliferation of fibrous tissue
- Developmental abnormality of bone forming mesenchyme
- Primitive fibrous tissue proliferates in bony medulla, causing arrest of bone maturation
- Bone is distorted with a smooth external surface
- Medullary cavity replaced by gray-white tissue of rubbery consistency, which is usually gritty on palpation
- Histology : Fibrous / collagenous tissue with poorly oriented fibre / bone trabeculae, formed by osseous metaplasia of fibrous tissue
- Multi-nuclear giant cells (3 – 20 nuclei) and foam cells may be seen with irregular spicular masses of bone, lying in the fibrous matrix
- The cells are well-spindled and the nuclei are elongated and densely chromatic with considerable amounts of intercellular collagen
- There is a lack of osteoblasts lining the bony trabeculae
- Bone is usually primitive (woven) in type, rather than lamellar and coarse fibred, containing numerous large lacunae with young cells
- Small masses of cartilage are often found in about 10%
- Histology : Appearance of alphabet soup
- Periosteal reaction to fracture is normal, but endosteal callus formation is poor
- Malignant transformation occurs in less than 0.5%
- Increased pain or sudden progression may indicate malignancy (osteosarcoma most common form)
Differential Diagnosis
- Secondary hyperparathyroidism (Brown tumour)
- Solitary bone cyst
- Solitary or multiple enchondromata
- Fibrous defects / non ossifying fibroma
- EG
- Neurofibromatosis
- Paget’s disease
- ABC
Treatment
- Indicated in pathological fracture, deformity or significant pain
- Biopsy may be necessary for correct diagnosis
- Lesions may recur after surgery
- If using bone grafts, use cortical struts as cancellous bone becomes dysplastic
Prognosis
- Spontaneous regression of lesions has never been observed
- Lesions progress in childhood, but stabilise with skeletal maturity
- Pregnancy may stimulate activity in fibrous dysplasia
- May lead to skeletal deformity
- Sarcomatous change occurs in a very low number of cases
- Recurrence rate in the Mayo clinic series was 21% for all methods of treatment of monostotic fibrous dysplasia as opposed to 36% for all methods of treatment of polyostotic fibrous dysplasia
Fibrodysplasia ossificans progressiva (Myositis Ossificans Progressiva)
Inheritance
- Autosomal dominant (most sporadic)
- Usually evident before 10 years
- Male : Female 4:1
Clinical Features
- Occasionally features evident at birth
- Short hallux and thumb evident at birth
- Egg shaped swellings appear first in neck, dorsal trunk and shoulder girdle, which may be fluctuant with crepitus or hard from the outset
- Associated with low grade fever
- Torticollis is a common presenting complaint Involvement of limbs distal to knees & elbows is rare
- Does not involve smooth or cardiac muscle
X-Rays
Columns of extra-skeletal bone of varying density
Pathology
- Defect of connective tissue (myositis is a misnomer)
- Progressive calcification : ossification of fascia, aponeurosis, ligaments, tendons, and connective tissue of skeletal muscle
- Marked interstitial edema is a feature
Differential Diagnosis
- Congenital muscular torticollis (thumb and toe normal)
- Dermatomyositis
Treatment
- No specific treatment
- Unable to alter course of disease
Prognosis
- Steady progression of contracture, muscle wasting, etc.
- Periods of acute exacerbation and remission
- Leads to total disability
Nail patella syndrome
Characterised by abnormalities of nails, elbows and knees
Inheritance
- Autosomal dominant
- Linked to gene for ABO blood group
Clinical Features
- Nail dystrophy most severe in thumbs (present in 98%)
- Little finger rarely affected
- Thumb nail may be absent, bifid or hemiatrophic
- Absence or hypoplasia of patella
- May present with recurrent dislocation
- Associated hypoplasia of lateral femoral condyle
- Increased carrying angle and hypoplasia of lateral side of elbow, which may result in subluxation of radial head
- Associated with two types of pelvic dysplasia : "Iliac horns" (present in 75%) and prominence of ASIS
Treatment
- No specific treatment
- May require quads-plasty or realignment
Marfan disease
Inheritance
Autosomal dominant (variable expression)
Incidence
About 3 / 100,000 (25 – 30% appear to be new mutations)
Clinical Features
- Tall stature (more than 182 cm), with disproportionate long limbs
- Lower segment length more than upper segment
- Arm span usually exceeds total height
- Long thin face with normal intelligence
- Elongated digits
- Dislocation of lens and extreme myopia and strabismus may be present
- Also associated with cardiac abnormalities, e.g. mitral valve prolapse (80%), aortic dilatation, dissection and rupture are common
- Pectus excavatum
- Ligamentous laxity and joint hypermobility may lead to pes valgus & genu recurvatum
- Patella alta with tendency to dislocation
- Thumb protrudes beyond ulna border of clenched fist
- Hernias are common
- Scoliosis present in 50% of cases, often painful, early onset with rapid progression
- Spondylolisthesis is also common
Diagnostic Criteria
- Positive family history
- Cardiac disease (dilation of ascenting aorta & mitral valve prolapse)
- Dislocation of lens (upwards and outwards)
- Musculoskeletal anomalies (scoliosis, ligamentous laxity, flat foot, spondylolisthesis, pectus excavatum, etc.)
Pathology
Defect in fibrilin component of elastin with reduced tensile strength
Treatment
- No specific treatment
- Orthopaedic measures directed toward scoliosis and joint laxity (pes valgus & patella dislocations)
Homocystinuria
Aetiology
An inborn error of methionine metabolism, due to the deficiency of the enzyme cystathionine synthase
Inheritance
- Autosomal recessive
- Results in increased cystine in fibrilin, with similar features to Marfans
Clinical Features
- Similar to Marfans, but with mental retardation and joint stiffness rather than laxity
- Contracture of fingers is a feature
- Pes cavus
- Scoliosis (30%)
- Kyphosis
- Genu valgum
- Dislocation of the lens (but downwards and inwards)
Investigation
Cyanide-nitroprusside in urine to detect homcystinuria in neonatal period
Treatment
- High doses of Vitamin B6 (effective in about 50% of patients)
- Low methionine diet
- Antithrombodic doses of aspirin
Acrocephalosyndactyly (Aperts disease)
Characterised by premature closure of cranial sutures and complex syndactyly of the hands and feet
Inheritance
Autosomal dominant
Clinical Features
- Head is peaked and vertically elongated
- Exophthalmos secondary to increased ICP
- Syndactyly of digits may be complete or partial
Treatment
Neurosurgical skull osteotomy and interposition
Ehler’s Danlos Syndrome
Inheritance
- Autosomal dominant with wide variance in expression
- Extensive genetic heterogenicity
Aetiology
- Uncommon familial disorder of connective tissue relating to a genetic defect in Type I collagen
- There are a number of genotypes related to this condition (11)
- Results in joint and skin hyperextensibility, easy bruising, increased joint mobility and abnormal tissue fragility
Clinically
- All patients have soft fragile skin and a tendency to form tissue paper scars
- Associated with hypermobile joints and hernias
- There are several distinct types, but further heterogeneity is obvious within each group
- Patients bruise easily
- Narrow maxilla and hypermobile ears
- Mitral valve prolapse and dilation of aortic root or sinus may occur
- Associated with severe talipes equino varus, ocular and gastrointestinal anomalies
- Wounds heal slowly and prolonged haemorrhage may follow trauma
- Serious complications may arise from ruptured aneurism