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Congenital Malformations Of Bone
(Skeletal Dysplasia)
Dr. Apoorv JainD’Ortho, DNB Ortho
[email protected]+91-9845669975
• The Word dysplasia originates from the ancient greek words dys(anomalous) & plasia(formation)
• Skeletal dysplasia is a heterogeneous group of congenital anomalies characterized by the abnormalities in the development of Bone and cartilagenous tissues
Normal Bone DevelopmentOn the basis of development, the bones are of 2 types:• Intramembranous bones• Endochondral bones
Intramembranous Ossification: Bone is directly laid down in membranous
sheets without any cartilaginous model
(Eg: Clavicle, Facial bones and Bones of the Skull vault)
Endochondral Bones: The formation of bone is preceded by the formation of a cartilaginous bone model which is replaced by bone (Eg: Bones of the limbs except clavicle, trunk and base of the skull)
Classification Of Skeletal Malformations(By Agerter and Kirkpatrick, 1975)
1) Disturbances in Chondroid Production:Abnormal Maturation of Chondroblasts:
• Mucopolysaccharidosis• Idiopathic:
–Achondroplasia–Cartilage-Hair Hypoplasia–Metaphyseal Dysostosis
Heterotopic Proliferation Of Chondroblasts:
-Enchondromatosis (Dyschondroplasia , Ollier’s disease)-Osteochondromatosis (Multiple Heriditary Exostosis)-Epiphyseal Hyperplasia
2. Disturbances in Osteoid production:A) Abnormal Epiphyseal Ossification:
-Diastrophic Dwarfism-Spondyloepiphyseal Dysplasia-Multiple Epiphyseal Dysplasia (Includes Blount’s and Pseudochondroplasia)-Stippled Epiphysis
B) Abnormal Metaphyseal and Periosteal Ossification:1) Deficient Osteoid Production:
-Osteogenesis Imperfecta2) Excessive Osteoid production or Decreased
Osteolysis: -Osteopetrosis -Pykindysostosis -Metaphyseal Dysplasia -Diaphyseal Sclerosis -Melorheostosis -Osteopathia Striata -Osteopoikilosis
C) Abnormal Osteoid Production:-Polyostotic Fibrous Dysplasia-Neurofibromatosis-Congenital Pseudoarthrosis
3) Miscellaneous Dysplasias: Marfan’s Syndrome Apert’s Syndrome Cleidocranial Dysostosis Chondroectodermal Dysplasias
EVALUATION OF APATIENT WITH
SKELETAL DYSPLASIA
Prenatal Diagnosis• Prenatal Ultrasound– Identify
lethal dysplasias –Diagnosis based on femoral length,
head circumference, body ratios and fetal characteristics typical of skeletal dysplasias
• Genetic analysis –Chorionvillous biopsy–Amniocentesis
Postnatal DiagnosisTHREE CLINICAL QUESTIONS:• Is the child abnormally small or
large?• Is stature proportional or
disproportional?• Dysmorphic facial features?
• Short Limb –Achondroplasia –Hypochondroplasia –Chondrodysplasia punctata –Achondrogenesis –Thanatophoric dysplasia
• Short Trunk/limb –Spondyloepiphyseal dysplasia
Long Bones:• The long bones in all of the extremities
should be measured.• If limb shortening is present, the
segments involved should be defined.• A detailed examination of the involved
bones is necessary to exclude absence, hypoplasia, and malformation of the bones.
• The bones should be assessed for presence, curvature, degree of mineralization, and fractures.
• The femur length–abdominal circumference ratio (<0.16 suggests lung hypoplasia) and femur length–foot length ratio (normal = 1, <1 suggests skeletal dysplasia) should be calculated.
Thorax:• The chest circumference and
cardiothoracic ratio should be measured at the level of the nipples or 5th intercostal space.
• A chest circumference less than the 5th percentile for gestational age (8–10) has been proposed as an indicator of pulmonary hypoplasia.
The chest diameter should be between 80-100% of the abdominal diameter.
• The shape and integrity of the thorax should be noted.
• Abnormal rib size and configuration are also seen in patients with lethal skeletal dysplasias.
• The clavicles should be measured, since absence or hypoplasia of the clavicles is seen in cleidocranial dysplasia.
• The presence of the scapula should also be noted, since its absence is a useful defining feature of camptomelic dysplasia.
Hands and Feet:The hands and feet should be evaluated to exclude the presence of(a) Polydactyly (the presence of more than five digits)[Preaxial if the extra digits are located on theradial or tibial side and postaxial if they are located on the ulnar or fibular side](b) Syndactyly (soft-tissue or bone fusion of adjacent digits).(c) Clinodactyly (deviation of a finger) and otherdeformities.
Example Of Post-axial Polydactyly
Bony Syndactyly Clinodactyly
• “Radial-ray” anomalies range from abnormal thumbs to hypoplasia or absence of the thumb and sometimes absence of the radius or even the radius and the hand.
• The three most likely diagnoses include:
Holt-Oram syndrome, the thrombocytopenia-absent radius (TAR) syndrome and trisomy 18.
Skull:• Head circumference and biparietal diameter
should be measured to exclude macrocephaly.
• The shape, mineralization, and degree of ossification of the skull should be evaluated.
• Interorbital distance should be measured by using the binocular diameter and interocular diameter to exclude hyper- or hypotelorism.
Normal Skull
Scaphocephaly Brachycephaly
Craniosynostosis seen in conditions like:Thanatophoric dysplasia,Carpenter's syndrome,Hypophosphatasia,Crouzon – Aperts.
Wormian bones seen withCleidocranial dysplasia,Osteogenesis imperfecta,Trisomy 21,Hypothyroidism,Progeria.
Spine:• The spine should be carefully imaged to assess
the relative total length and the presence of curvature to exclude scoliosis.
• Mineralization of vertebral bodies and neural arches should be evaluated.
• Vertebral height should be subjectively evaluated for platyspondyly (flattened vertebral body shape with reduced distance between the endplates), which is typically seen in thanatophoric dysplasia.
Pelvis:• The shape of the pelvis can be important in
certain dysplasias, such as limb-pelvic hypoplasia.• Femoral hypoplasia–unusual face syndrome
(hypoplastic acetabulae, constricted iliac base with vertical ischial axis, and large obturator foramina).
• Achondroplasia (flat, rounded iliac bones with lack of iliac flaring; broad, horizontal superior acetabular margins; and small sacrosciatic notches).
University of Washington Medical Center Worksheet while evaluating a patient suspected skeletal dysplasia
RADIOGRAPHIC EXAMINATION:• A complete skeletal survey should be done
in children >6 months. • In newborns and infants <6 months, at least–AP and lateral films of the whole spine –AP films of the hands –Lateral skull –Lateral cervical spine flexion and extension
Hypoplastic scapulae in campomelic
dysplasiaThoraco Lumbar Kyphosis as seen in Achondroplasia
and Sponyloepithelial dysplasia
Cervical Instability(Can be seen in every dysplasia except
Achondroplasia)
Cervical Instability on MRI
Platyspondyly and Thickened, Shortened small bones commonly seen in Mucopolysaccharidosis
Final Diagnosis• Prenatal/Postnatal onset • Skeletal features
–short limb/short trunk –acro, meso or rhizomelia
• Extra skeletal features • Family history • Radiographic characteristics • Laboratory • Genetic analysis
Skeletal dysplasias include more than 380 conditions leading to abnormally developed bones and
connective tissues
Osteogenesis Imperfecta
Synonyms• Fragilis osseum• Osteopsathyrosis idiopathica• Brittle Bone disease• Glass Bone disease• Periosteal dysplasia• Lobstein’s disease• Vrolik disease• Porak and Durante’s disease
Introduction
• It is a genetic disorder of connective tissue with clinical features of increased bone fragility
• It maybe inherited as Autosomal Dominant or may occur as spontaneous mutation or rarely inherited as a homozygous Autosomal Recessive trait
Introduction…
• Major clinical features include Skeletal deformity, Blue sclerae, Fragile opalescent teeth (Dentinogenesis imperfecta)
• Less severe manifestations include generalised ligamentous laxity, hernias, easy bruisability and excessive sweating
Normal Collagen Metabolism
• Collagen is a connective tissue protein with a left handed triple helical structure
• Type I Collagen composed of 2 α1(I) strands and 1 α2(I) strand
• In fibroblasts the precursors are synthesized in RER– Pro α1(I) encoded by COL1A1 on Chr. 17
– Pro α2(I) encoded by COL1A2 on Chr. 7
Normal Collagen Metabolism
• 2 Pro α1(I) + 1 Pro α2(I) type I Procollagen beginning at the C end and propagating towards the Amino terminal
• Cross linking - Gly residues; every 3rd position• Type I Procollagen is secreted from the cells
and processed extracellularly to form Type I Collagen molecule
Collagen Metabolism in OI
• 90% have an identifiable genetically determined defect, either qualitative or quantitative, in type I Collagen formation
• Assayed from cultures of fibroblasts from skin biopsies using electrophoresis
Classifications
• Looser (1906) classified into two typesCongenita – Numerous fractures at birthTarda – Fractures after perinatal period
• Shapiro subclassified either of these categories into Type A and Type B
• Shapiro’s classified OI into 4 types based on prognosis for survival and ambulation
OI Congenita AFractures in utero or at birthStill born or die shortly after birth
OI Congenita BFractures at birthLong bones are more tubular and more normal funnelization in the metaphysis
OI Tarda AOnset of fractures prior to walking
OI Tarda BFirst fracture after walking
Type I Type IIMost Common, ADQuantitative defectMild formDistinct blue sclerae throughout lifePremature arcus senilisPresenile conductive Hearing Loss
? AR, Most severe formSevere qualitative defect Extreme bone fragilityDeath in perinatal period or early infancyCrumbled long bonesMarked delay in ossification of skull bones
Sillence and Dank – 4 types(Clinical & Genetic characteristics)
IA – Normal TeethIB – with Dentinogenesis imperfecta
Type III Type IVAR or Dominant NegativeQualitative & quantitative defectSevere bone fragilityMultiple fractures, deformitiesSevere growth retardationSclerae are bluish at birth, become less blue with age and attain normal hue in adolescence
ADQualitative & quantitative defectSclerae are usually normal hue at birth
Sillence and Dank – 4 types(Clinical & Genetic characteristics)
IVA – Normal Teeth
IVB – with Dentinogenesis imperfecta
Histopathology• Bone trabeculae are thin and
lack an organized trabecular pattern
• The spongiosa is scanty and intercellular matrix is reduced
• Tetracycline labeled studies confirm increased bone turnover
Clinical Features(Severe form)
• Multiple fractures from minimal trauma
• Deformed and short limbs
• Soft and membranous skull
• Usually fatal• Death secondary to IC
hemorrhage or respiratory insufficiency
Clinical Features (Non Lethal forms)
• Increased fragility of bones (earlier the fracture, more severe the disease)
• Lower limbs are most commonly affected• Femur more commonly affected than tibia• Fractures heal at a normal rate• Non-union is relatively rare• Frequency of fractures decline sharply
after adolescence although it may rise again in postmenopausal women
• Bowing of long bones• Coxa vara• Short stature• Hypermobility of joints• Hypotonic muscles• Thin and translucent skin, subcutaneous
hemorrhages• Excessive sweating due to resting
hypermetabolic state• Heat intolerance• Metabolic acidosis• Cardiac arrhythmia
Skull• Forehead broad with prominent
parietal and temporal bones and overhanging occiput
• Triangular elfin shaped face• Ears are displaced downwards and
outwards• The configuration of Skull in OI is
called ‘Helmet head’
• Severe spinal deformities (Scoliosis and Kyphosis)– Osteoporosis– Compression fractures– Ligamentous hyperlaxity
• Scoliosis in 20 – 40% cases, Most commonly Thoracic scoliosis
• Spondylolisthesis• Cervical anomalies
Spine
• Blue Sclerae• Saturn’s ring• Hyperopia• Arcus juvenilis• Retinal detachment
• Deafness (40% in Type I, less in Type IV)– Conductive– Otosclerosis or– Nerve deafness
Eye
Ear
• Dentinogenesis imperfecta (Hereditary Opalescent Dentine or Hereditary hypoplasia of dentine)
• In Type IB and Type IVB• Enamel normal; teeth
break easily – prone to caries
• Lower incisors, which erupt 1st most severely affected
Teeth
Radiologic FeaturesSevere Form
• Short long bones with thin cortices
• Wide diaphysis• Numerous # in various
stages of healing• Multiple rib # and atrophy
of thoracic cage• Goldman described
‘popcorn’ calcification in the metaphysial and epiphysial area (resolves after completion of skeletal maturity)
Radiologic FeaturesSevere Form
Skull• Mushroom appearance
with thin calvarium• Delay in ossification• Wormian bones
Radiologic FeaturesSevere Form
Spine• Osteoporosis• Compression #• Biconcave compressed
vertebral bodies in between bulging discs
• Kyphoscoliosis
Radiologic FeaturesMilder Forms
• Similar picture of osteoporosis
• Bowing• Fractures in various
stages of healing• Callus typically wispy
but on rare occasions, it maybe very large and hyperplastic resembling Osteosarcoma
Hyperplastic Callus & Tumors in OI
Clinical FeaturesAcute localised inflammationProgressive enlargement of the limb
InvestigationsESR – Alk Phosphatase – X-ray – enlarging irregular callus mass
TreatmentSymptomatic – splinting? IrradiationDiphosphonates
Final Diagnosis
• Diagnosis is by–Positive family history–Clinical and radiologic findings
• Type I Collagen assay• Antenatal Diagnosis – USG and
Chorionic Villous Sampling
Treatment
• No specific treatment• Rehabilitation – protective bracing and
physiotherapy• Medical
– Biphosphonates – Pamidronate– Gene Therapy– Bone Marrow Transplantation
Orthopaedic Treatment
Goal• Improve function• Prevent deformity and disability• Correct deformities• Monitor for complications
Management Of Long Bone Fractures
• Depends on severity and age of the patient• Fractures should be immobilized only until
symptoms subside• As a general principle, intramedullary
fixation is preferable to plate and screws whenever possible because of the stress risers produced by the later
• Nonunion is rare
Management Long Bone Deformity• Indications for Surgery
– Repeated fractures induced by the deformity– To apply bracing for either protection against
further fractures or aid in ambulation• Treatment options
– Closed osteoclasis without internal fixation– Closed osteoclasis with percutaneous IM
fixation– Open osteotomy (fragmentation) + IM fixation
- Sofield procedure
Management of Spinal deformity
• Patient may not tolerate orthosis• Spinal fusion for severe progressive
deformity• Posterior stabilisation with Luque
sublaminar wires or tapes appears to be ideally suited for instrumentation in management of difficult cases
Blount’s Disease
Introduction• Tibia vara is defined as the growth retardation of
the medial aspect of the proximal tibial epiphysis usually resulting in progressive bow leg. Classified into three groups as– Infantile < 3years– Juvenile 4 – 10 years– Adolescent > 10 years
• Blount classified Tibia vara as– Infantile < 8 years (known as Blount’s Disease)– Adolescent > 8 years
Blount’s Disease• Erlacher (1922)• Blount (1937)• Synonyms
– Infantile Tibia vara– Erlacher’s disease– Blount-Barber syndrome– Deformative osteochondrosis of the tibia– Nonrachitic bowleg in children– Osteochondritis deformans tibiae– Subepiphyseal osteochondropathy
Etiology• Familial: Autosomal Dominant inheritance• Developmental• Multifactorial:
–Infection–Trauma–AVN–Latent form of rickets
• Others: early weight bearing, obesity
Histology• The physeal cell columns become irregular
and normal endochondral ossification is disrupted in the medial aspect of metaphysis and physis
• Islands of nearly acellular fibrocartilage• Islands of densely packed cartilage cells
with greater hypertrophy than expected from their position in the growth plate
• Large clusters of capillary vessels
Clinical Features• Similar to physiological genu varum with 2
major differences– Usually obese and start walking early– Clinically apparent lateral thrust to the knee
during the stance phase• Usually bilateral and symmetrical (60%)
and varus deformity increases progressively• Varus, internal tibial torsion and genu
recurvatum, plano valgus develops secondarily
• Siffert – Katz sign
Radiological Features• Varus angulation at epiphysio-
metaphyseal junction• Widened and irregular physeal
line medially• Medially sloped and irregularly
ossified epiphysis, sometimes triangular
• Epiphysis short thin and wedged• Prominent beaking of the medial
metaphysis, with lucent cartilage islands within the beak
• Lateral subluxation of the proximal tibia
Radiological Features
• According to Smith, medial metaphysial fragmentation is pathognomonic for the development of a progressive tibia vara
Tibio Femoral Angle Metaphysio Diaphysial angle(Levin and Drennen)
MD angle
Other Imaging Modalities• MRI: Able to demonstrate
the extent of the ossified and cartilaginous epiphysis along with any physeal anatomical disruption
• Arthrography: Dalinka demonstrated hypertrophy of the medial meniscus and the unossified cartilage of the medial tibial plateau
CT Scan• Greene listed the following criteria for
preoperative CT to determine if a bony bar is present– Age > 5 years– Medial physeal slope 50 – 70 degrees– Stage IV X-ray findings– Weight more than 95th percentile– Black female who meet the following
criteria
Langenskiold classification (1952)
• I - Irregular metaphyseal ossification combined with medial and distal protrusion of the metaphysis
• II, III, IV - Evolves from a mild depression of the medial metaphysis to a step-off of the medial metaphysis
• V - Increased slope of medial articular surface and a cleft separating the medial and lateral epicondyle
• VI - Bony bridge across the physis
Depending on degree of metaphysial and epiphysial changes on radiograph
Prognosis Based On Langenkiold classification
• Better prognosis in earlier stages– I & II can predictably have full restoration
with single osteotomy and bracing; treatment must be completed before 4 years
– III maybe restored– IV – VI requires complex reconstruction and
physeal procedures with guarded outcome at best
Treatment• Untreated infantile tibia vara
generally results in progressive varus deformity, producing joint deformity and growth retardation.
• Treatment choices and prognosis depend greatly on the age of the patient at the time of diagnosis.
Orthotics• Recommended for patients < 3 years of age and
<stage II disease• Rainey et al recommended KAFO that produced a
valgus force by three point pressure• Risk for failure included ligamentous instability,
patient weight above 90th percentile and late initiation of bracing
• Elastic Blount brace, a medial upright design with drop lock knee hinge that can be locked to increase the effectiveness of valgus pressure during weight bearing
Corrective Osteotomy
• Beatey et al recommended valgus osteotomies of proximal tibia and fibula with mild overcorrection in young children
• Early osteotomy produced best results chance of recurrence increased with increasing age
• Greene described Chevron osteotomy in which opening and closing wedges can be made so that the limb length deformity present in moderate to severe tibia vara will not be increased.
• He described a crescent shaped osteotomy using one half lateral closing wedge and using the graft medially in an opening wedge to maintain length.
• In children older than 9 years with more severe involvement, osteotomy alone, with bony bar resection, or with epiphysiodesis of the lateral tibial and fibular physes may be indicated.
Achondroplasia
• Achondroplasia is a type of short-limbed dwarfism
• It occurs when the process by which cartilage is converted to bone, or ossification, is stunted
• This is most apparent in the long bones of the arms and legs
• Incidence is 1 in 25,000 live births
Etiology• Autosomal dominant
inheritance• Due to mutations of the
FGFR3 gene on the short arm of chromosome 4
• This gene regulates bone development, so when affected, it causes malfunctions in bone growth
Clinical Presentation• Short arms and legs:
particularly the upper arms and thighs
• Enlarged head (macrocephaly) • Prominent forehead• Short fingers: the middle and
ring fingers may diverge, giving the hand a three-pronged (trident) appearance
• Sleep apnea • Persistent ear infections • Exaggerated Lumbar Lordosis• Bowed legs• Mid-face hypoplasia• Hypotonia: low and weak muscle tone • Delays in walking and other motor skills • Back pain• Obesity• Bowed legs• Limited range of motion at the elbows
Diagnosis
• Characteristic clinical findings• X-ray findings• Genetic analysis
Treatment• There is no specific or permanent treatment. • Measures to avoid obesity are taken. • To correct obstructive sleep apnea, a surgical
opening in the airway, or tracheostomy, can be performed.
• With patients with problems such as hyperreflexia, clonus, or central hypopnea: suboccipital decompression, which decreases pressure on the brain can be done.
• Growth hormones and/or surgery may be able to lengthen limbs, but only up to a certain limit.
Marfan’s Syndrome
Description•Heritable disorder of the connective tissue•Connective tissue affects:
•Growth and development•Cushioning of joints•Vital organs
•1 in 5,000 people in US have disorder
Symptoms
• Affects many body systems including:– Skeleton– Eyes – Heart and Blood Vessels – Nervous System– Lungs– Skin
Skeleton• Tall and slender• Disproportionately long appendages• Indented or protruding sternum• Arched palate, overcrowded teeth, receding
mandible• Curvature of spine
Eyes• Off-center or dislocated
lenses• Nearsightedness (Myopia)• Development of cataracts at
a younger age (30s to 50s)• Retinal detachment
• Stretch marks– Shoulders, hips, lower back
• Increased risk for abdominal hernias
Skin
Heart and Blood vessels• Weakened middle layer of
aortic wall– Stretched aortic valve leaflets– Aneurysm may form
• Aortic regurgitation– Left ventricle must compensate– Chest pain, heart failure
• Tears in inner and middle aortic layers– Middle layer separates– New channels for blood flow
Nervous System
• Stretching and enlargement of dura membrane– Pushes on and wears down vertebrae– Can protrude through vertebral column and into abdomen– Dural cysts
• Increased susceptibility to learning disabilities
Lungs• Diminished alveoli elasticity• Susceptibility to asthma,
bronchitis, pneumonia– In rare cases, develop
emphysema• 5% experience spontaneous
lung collapse• Sleep disordered breathing
– Snoring most common– Caused by partial obstruction of
airway by connective tissue
Basic Genetic Information
• Autosomal Dominant• Dominant Negative Mutation – the altered
gene product antagonizes the product of the normal gene
• Haploinsufficiency – when a diploid organism has only one functional copy of a gene, the other copy being mutated
• Affects FBN-1 Gene
FBN-1 Gene• Located on chromosome 15• Codes instructions for the
creation of protein Fibrillin 1• Marfan’s is caused by over
500 different mutations on FBN1
• 60% mutations are change in one protein building block.
• 40% mutations produce small protein that can’t function
Fibrillin 1 protein
• Connect with other Fibrillin 1 proteins to make microfibrils, which become connective tissue.
• Microfibrils mainly trap transforming growth factor-beta (TGF-beta) and keeps them inactive.
Defective Fibrillin 1 Protein
• Amount of fibrillin 1 protein produced by cells is reduced
• Structure and stability of protein is affected• Transport of fibrillin 1 protein out of the cell is
impaired• Amount of fibrillin 1 reduced means
decreased microfibril production• Less microfibril leads to more active TGF-beta,
which leads to Marfan’s symptoms
Testing and Diagnosis
• Genetic analysis:–Types
• Complete bi-directional DNA sequencing
• FBN1 gene sequencing • TGFBR gene sequencing • Familial mutation test
• Other– Imaging tests
• Chest x-ray• MRI
– Symptoms checklist• Family history + 2
affected body systems• At least 3 affected
body systems
• Index case:Major criteria in 2 different organ systems AND involvement of a third organ system.
Relative of index case:1 major criterion in family historyAND 1 major criterion in an organ systemAND involvement in second organ system.
SKELETALMajor (Presence of at least 4 of the following manifestations)__ pectus carinatum__ pectus excavatum requiring surgery__ reduced upper to lower segment ratio (Note 1) OR arm span to height ratio >1.05Height ____ Arm span ____ Upper segment ____ Lower segment ______ wrist (Note 2) and thumb (Note 3) signs__ scoliosis of >20° or spondylolisthesis__ reduced extension at the elbows (<170°)__ medial displacement of the medial malleolus causing pes planus__ protrusio acetabulae of any degree (ascertained on radiographs)Minor__ pectus excavatum of moderate severity__ joint hypermobility__ high arched palate with crowding of teeth__ facial appearance__ dolichocephaly,__ malar hypoplasia,__ enophthalmos,__ retrognathia,__ down-slanting palpebral fissures
Diagnostic ChecklistOCULARMajor__ ectopia lentisMinor__ flat cornea__ increased axial length of the globe__ hypoplastic iris OR hypoplastic ciliary muscle causing decreased miosis
CARDIOVASCULARMajor__ dilatation of the ascending aorta with or without aortic regurgitationand involving at least the sinuses of Valsalva__ dissection of the ascending aortaMinor__ mitral valve prolapse with or without mitral valve regurgitation__ dilatation of the main pulmonary artery, in the absence of valvular orperipheral pulmonic stenosis below the age of 40 years__ calcification of the mitral annulus below the age of 40 years__ dilatation or dissection of the descending thoracic or abdominal aortabelow age of 50 years
PULMONARYMinor (only)__ spontaneous pneumothorax__ apical blebs
SKIN AND INTEGUMENTMinor (only)__ striae atrophicae__ recurrent or incisional hernia
DURAMajor__ lumbosacral dural ectasia by CT or MRI
FAMILY/GENETIC HISTORYMajor__ first degree relative who independantly meets the diagnostic criterian.__ presence of mutation in FBN1 known to cause Marfan syndrome__ presence of haplotype around FBN1 inherited by descent and unequivocallyassociated with diagnosed Marfan syndrome in the family
• Positive Steinburg Thumb Sign
Positive WalkerWrist Sign
Treatment• Require a multidisciplinary team• Symptoms, not disorder, must be
treated• Yearly echocardiograms• Emotional support• Healthy Diet
Heart• Enlargement of the aorta
– Aortic Dissection• Aortic Dilation
– Aortic Valve regurgitation– Mitral valve prolapse
• Medications– Lower blood pressure– Angiotensin receptor blockers– Beta blockers
• Regular Echocardiograms
Skeleton
• Physiotherapy• Pain Clinics
–Loose joints• Bracing
–Back–Ankle
• Surgery–Pectus excavatum
Physical Activity
• Avoid contact and strenuous sports because of the risk of damaging the aorta and injuring the eyes
• Individual restrictions based on severity and discussed with physician
Apert’s Syndrome
• Described first by a French physician in 1906
• Also known as ACROCEPHALOSYNDACTYLIA
• A genetic disorder with Autosomal Recessive inheritance
• Affected gene is called FGFR2 (Fibroblast Growth Factor Receptor 2)
• Locus on chromosome is 10q26
• All groups are affected–Most prevalent in Asians;
• Incidence in Asians is 22.3 per million births
• Age of onset is at birth• Diagnosed at birth itself due to
peculiar features like syndactyly and shape of the skull
Clinical Signs• Early closure of sutures between the
bones in the skull• Frequent ear infections• Fusion or severe webbing of the 2nd,
3rd, and 4th fingers– “mitten hands”
• Hearing loss• Large or late-closing soft spot on a baby’s
skull• Possible, slow intellectual development
• Severe under-development of the mid-face
• Skeletal (limb) abnormalities• Short height• Webbing or fusion of the toes• Prominent or bulging eyes
Frequently Associated Conditions
• Dextrorotation• Pulmonary Atresia• Patent Ductus
Arteriosus (PDA)• Tracheoesophageal
Fistula• Pyloric stenosis• Polycystic Kidneys
• Ear infections• Sleep Apnea• Severe acne• Hydrocephalus• Bicornate uterus
Treatment-Separation of the abnormally fused skull bones to allow for the growth of the head
Done in infancy-Correction of midface hypoplasia using the Ilizarov procedure
Opens up the bones of the middle of the face and stimulates them to grow
Done between ages 6-11-Separation of fingers and toes
Correction of midface hypoplasia using the Ilizarov procedure
Osteopetrosis
• Also known as Marble bone disease and Alber Schonberg’s disease
• Developmental abnormality in which the bones throughout the body become increasingly dense and brittle
Etiology• Defective Carbonic anhydrase function• Lack of alkaline environment for
osteoclast function• Defective osteoclast function• Continued new bone deposition with no
resorption• Bones are hard as marble or can be
brittle like a chalk and are grey or white on cut section
• The medullary cavity is obliterated and deficient in bone marrow leading to pancytopenia and reduced immunity.
• Bony encroachment on cranial foramina can produce optic atrophy deafness and facial paralysis.
Types • Infantile osteopetrosis:
– Autosomal recessive– Severe form– Poor prognosis– Usually patient dies by 2 years of age
• Benign adult osteopetrosis:– Autosomal dominant– Less severe form (usually detected
incidentally), Good prognosis
Clinical Features• Shape of head (Box like appearance)• Hepatosplenomegaly• Lymphadenopathy• Optic atrophy, deafness or facial paralysis
in cases with stenosis of cranial foramen• Anaemia• Pancytopenia• Frequent infections and osteomyelitis
Radiological features• Increased density of all
bones with decreased remodelling.
• Widened shafts, decreased marrow space in long bones due to increased cortical thickness.
• Base of skull is thickened with narrowed cranial foramen.
• Paranasal sinuses : poorly pneumatized (ethmoid sinuses least severely affected)
• Calvarium : high-attenuation inner table, a broad, low-attenuation diploic space, and a less high-attenuation outer table
Blood Routine
• Anaemia• Pancytopenia• Most patients have normal levels of serum
Calcium, Phosphate and Alkaline Phosphatase.
• Recessive disease may have Hypocalcemia during infancy
Treatment
• Symptomatic treatment for pain relief• Bone marrow transplantation for
malignant/ lethal disease is the only treatment option
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