3/6/2017
Fetal Musculoskeletal System Skeletal Dysplasias & Skeletal Dysplasias • Why do we dread them? Mani Montazemi, RDMS Director of Ultrasound Education & Quality Assurance Baylor College of Medicine Division of Maternal-Fetal Medicine Maternal Fetal Center Imaging Manager Texas Children’s Hospital, Pavilion for Women Houston Texas & Clinical Instructor Thomas Jefferson University Hospital - Radiology Department Philadelphia, Pennsylvania Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Let me Count the Whys
1. Rare (2.4 per 10,000) 2. Most die (23% still born & 32% in 7days) 3. Nearly 300 different types 4. Only a few can be accurately diagnosed with targeted ultrasound 5. It’s life & death if you make a mistake
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Normal Skeletal Development
• 6 weeks – Vertebral bodies • 7 weeks – Skull • 8th weeks – Limb buds, Mandible, clavicle • 9th weeks – Femur, humerus • 10 weeks – Tibia / fibula, radius / ulna • 11weeks – Digits of hands & feet
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
1 3/6/2017
There’s more to What to Look For? • Length of extremities musculoskeletal • Shape of extremities evaluation • Mineralization • Movement than diagnosing • Associated abnormalities in other systems skeletal dysplasia…
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
What to Look For? Length of Extremities
• Length of extremities • Possible causes of long bone length less than 2 SD below the mean for gestational age – Incorrect dates – Abnormal karyotype – IUGR – Constitutionally short stature – Isolated skeletal anomaly – Skeletal dysplasia Ulna tibia… measurement
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Ratio Between the FL & Other Body Measurements Initial Questions • The femur length & foot are of comparable • What has been the interval growth of the femur length in the normal fetus length?
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
2 3/6/2017
Interval Growth of the Femur
• From 16 to 22 weeks gestation the mean length of all • Standard deviations below mean long bones increases by between 2.5-2.7 mm/week – 2‐3 often familial, anatomic variant, mild skeletal dysplasia – > 4 non-lethal skeletal dysplasia • A fetus with OI type II may have an abnormal FL at – > 6 invariably BAD prognosis 15 weeks gestation • The earlier long bone shortening is seen the worse it is • Late onset associated with familial conditions think • A fetus with heterozygous achondroplasia may not about growth restriction have abnormally short until 21-27 weeks gestation • Progressive shortening may be a clue to achondroplasia
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Ratio Between the FL & Initial Questions Other Body Measurements
• Is the ratio between the femur length and other • Femur length-HC ratio more than 3 SD below the body measurements appropriate? mean suggests a skeletal dysplasia • Femur length-AC ratio < 0.16 suggests lung hypoplasia
• Femur length-foot length ratio of <1 suggests skeletal dysplasia
• Chest circumference/abdominal circumference ratio < 0.8 suggests lethality
Mani Montazemi, RDMS Mani Montazemi, RDMS RSNA – Radiographics 2008; 28: 1061-1077 Musculoskeletal Anomalies Musculoskeletal Anomalies
What to Look For? What to Look For?
• Length of extremities • Length of extremities • Shape and fractures of extremities • Shape and fractures of extremities • Mineralization
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
3 3/6/2017
Hypophosphatasia What to Look For?
• Demineralized segment where the vertebral bodies • Length of extremities have a “ghost” outline and no acoustic shadowing • Shape and fractures of extremities • Mineralization • Movement
Trv proc
vertebral body
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
What to Look For? Narrow Chest
• Length of extremities • Hypoplastic thorax occurs in many skeletal • Shape and fractures of extremities dysplasias – Thanatophoric dysplasia • Mineralization – Achondrogenesis • Movement – Hypophosphotasia • Associated abnormalities in other systems – Camptomelic dysplasia – Head, Thorax & spine – Osteogenesis imperfecta – Chondroectodermal dysplasia – Short rib polydactyly
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Shortening of the Extremities Rhizomelia
• Rhizomelia • The proximal portion of the limb is reduced in • Mesomelia size (humerus or femur) • Micromelia • Acromelia
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
4 3/6/2017
Rhizomelia – Associated Findings Mesomelia
• Thanatophoric dysplasia • The mid-limb (ulna/radius and or tibia/fibula) • Atelosteogenesis is reduced in size • Chondrodysplasia punctata (rhizomelic type) • Diastrophic dysplasia • Congenital short femur • Achondroplasia
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Micromelia Micromelia
• The entire limb is reduced
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Micromelia – Associated Findings Acromelia
• Achondrogenesis • The hands or feet are reduced in size • Atelosteogenesis • Short-rib polydactyly syndrome (types I & III) • Diastrophic dysplasia • Fibrochondrogenesis • Osteogenesis imperfecta (type II) • Kniest dysplasia • Dyssegmental dysplasia
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
5 3/6/2017
Hands & Feet Abnormalities Polydactyly
• Polydactyly • Presence of additional digit • Oligodactyly • Range from a fleshy nubbin to a complete digit • Syndactyly with controlled flexion and extension • Clinodactyly • Amelia • Meromelia • Club Hand / Foot • Rockerbottom Feet • Sandal Toes
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Polydactyly Polydactyly
• More common in hands than feet • Postaxial polydactyly – ulnar side of the hand & fibular side of the foot • Preaxial polydactyly – Radial side of the hand & tibial side of the foot
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Polydactyly Oligodactyly
Preaxial • Fewer than 5 digits per extremity – Chondroectodermal dysplasia – Short-rib polydactyly syndrome type II – Carpenter syndrome Postaxial – Chondroectodermal dysplasia – Short rib-polydactyly syndrome (type I, type III) – Asphyxiating thoracic dysplasia – Otopalatodigital syndrome – Mesomelic dysplasia Werner syndrome (no thumbs)
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
6 3/6/2017
Syndactyly Syndactyly
• Fused digits, either cutaneous or osseous • Poland syndrome • Carpenter syndrome • Aper syndrome • Otopalatodigital syndrome (type II) • Mesomelic dysplasia Werner type • TAR syndrome • Jarcho-Levin syndrome • Roberts syndrome • Triploidy
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Clinodactyly Amelia
• Permanent bend in one or more digits or • Absence of the limbs persistently overlapping digits • Associated with trisomy 18
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Meromelia Club Hand
• Absence of the hands and most of the forearm Classified into two categories: • Radial club hand – Absent thumb – Thumb hypoplasia – Thin first metacarpal – Absent radius • Ulnar club hand (less common) – Mild deviations of the hand of the ulnar side of the forearm – Complete absence of the ulna
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
7 3/6/2017
Club Hand Club Foot
• All metatarsals (& toes) are visible in the same plane as the tibia & fibula, roughly perpendicular to them.
Clubbing of the hand and webbing at the wrist and elbow consistent with early onset of fetal akinesia Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Club Foot Club Foot: Associated Findings
• Medial deviation and inversion of the sole • Chromosomal abnormalities (tri 18 > 13) • Neural tube defect; CNS disorders • Familial history 15% • Neuromuscular disorders • Twice as frequent in males • Crowding: oligohydramnios, multiples, fibroids, amniotic bands • Other skeletal abnormalities – arthrogryposis, skeletal dysplasia, genetic syndromes • Heart defects, cleft lip, renal abnormalities
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Club Foot - Types
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
8 3/6/2017
Rocker-bottom Feet Sandal Toes
• Characterized by a prominent heel and a • Space between 1st & the 2nd toe (trisomy 21) convex sole • Associated w/ >30 malformation syndromes, especially trisomy 18
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Arthrogryposis Arthrogryposis
• Due to: – Neuropathic abnormalities – Muscular abnormalities – Connective tissue abnormalities – Space limitations within the uterus – Intrauterine vascular compromise
• Associated with: – Bilateral renal agenesis Contractures of the extremities – Spina bifida Hand is persistently flexed – Sacral agenesis – Metatrophic or diastrophic dwarfism Contracture of the ankle
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Arthrogryposis Abnormal skull Contour
• Frontal bossing – Thanatophoric dysplasia – Osteogenesis imperfecta
The legs are held in • Cloverleaf skull one position Unusual extension of – Homozygous achondroplasia both knees without postural change – Thanatophoric dysplasia Both hand and fingers show contracture and abnormal angulation deformities Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
9 3/6/2017
Frontal Slanting
• Scaphocephaly • Microcephaly
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Sagittal View – Facial Profile Mandible Anomalies
• Part of more than 100 genetic syndromes Nasal bone Frontal bone • Micrognathia * – Insufficient size • Retrognathia Maxilla – Recession of the chin
Mandible
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Facial Profile View
Micrognathia • small chin – prominent upper lip – Otocephaly – Pierre Robin sequence – Fetal alcohol syndrome – Achondrogenesis – Triploidy & trisomy 18 & 13 Prognathia Micrognathia Retrognathia
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
10 3/6/2017
• Severe Kypho-scoliosis • Abnormal Neck/Chin • Webbing from arms to chest
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Skeletal Disorders
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Skeletal Dysplasia
• The term dysplasia means What is difficult? – Intrinsic growth disturbance occurring during the • Precise diagnosis of bone dysplasia early stages of fetal development
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
11 3/6/2017
Skeletal Dysplasia Clues to Lethal Skeletal Dysplasia
What is important? 1. Early onset severe limb shortening • Differentiation between a lethal and a non- 2. Small chest with short ribs 3. Fractures or marked bowing lethal variety 4. Clover leaf skull – Antenatal care 5. Hydrops – Prediction of fetal outcome 6. Demineralization 7. Early severe polyhydramnios
Femur/ abdominal circumference ratio < 0.16 suggests lethality Chest circumference/abdominal circumference ratio < 0.8 suggests lethality
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Lethal Skeletal Dysplasia is Not Subtle! Common Skeletal Dysplasias Osteochondrodysplasias Abnormalities of cartilage or bone growth & development
1. Thanatophoric Dysplasia (lethal)
2. Acondroplasia (usually not lethal)
3. Osteogenesis Imperfect (type II lethal) Vs. 4. Achondrogenesis (lethal) 5. Hypophosphatasia (some types lethal)
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Thanatophoric Dysplasia Thanatophoric Dysplasia - Features
• The most common lethal skeletal dysplasia • Long bones – Very short & curved • Name means “seeking death” • Head • Birth prevalence of ~ 0.7-0.8 in 10,000 – Macrocephaly – Frontal bossing + depressed nasal bridge • Prenatal genetic testing – Cloverleaf-shaped skull – Mutation in FGFR3 gene • Chest – Narrow thorax – Short ribs • Small short & wide iliac wings
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
12 3/6/2017
Thanatophoric Dysplasia Thanatophoric Dysplasia
• Narrow chest, protuberant abdomen, abnormal chest/abd ratio, bell-shaped • Short ribs
Mani Montazemi, RDMS Chest circumference/abdominal circumference ratio < 0.8 suggests “lethality” Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Thanatophoric Dysplasia Thanatophoric Dysplasia
• Micromelia (short limbs)
Platyspondyly
Disk interspace is larger than the height of the vertebral bodies
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Thanatophoric Dysplasia Thanatophoric Dysplasia
• Macrocrania, frontal bossing, depressed nasal bridge, cloverleaf shape • “Type I” (sporadic) 14% (type II) – Telephone receiver femurs
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
13 3/6/2017
Thanatophoric Dysplasia Thanatophoric Dysplasia
• “Type II” (autosomal recessive) • Small Thorax + short ribs – Femurs are straight but the skull is Cloverleaf shaped • Micromelia • Large head with a prominent forehead • Type I (sporadic) – Telephone receiver femurs • Type II (autosomal recessive) – Femurs are straight but the skull is Cloverleaf shaped • Severe polyhydramnios – early onset
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Thanatophoric Dysplasia Achondrogenesis
• Associated anomalies • Lethal skeletal dysplasia – Holoprosencephaly • Birth prevalence of about 1 in 40,000 – Agenesis of the corpus callosum – Ventriculomegaly – Horseshoe kidney – Hydronephrosis – Congenital heart disease
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Achondrogenesis Achondrogenesis
US Findings • Severe micromelia – Disproportionately large head – Prominent forehead • Redundant soft tissue – Depressed nasal bridge • Mimics hydrops – Small nose with anteverted nostrils – Increased distance between lip & lower edge of chin – Short neck – Narrow and short thorax – Very short limb, dwarfism – Distended abdomen – Polyhydramnios, early onset
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
14 3/6/2017
Achondrogenesis Achondroplasia
• Type I (autosomal recessive) – 20% • Most common heritable non-lethal skeletal dysplasia – Poor ossification of spine & skull • Most common cause of short stature with disproportionately short limbs – Short fractured ribs • An autosomal dominant condition • Type II (sporadic) – 80% • Birth prevalence of about 1 in 40,000 – Hypo-mineralization of the vertebral bodies • Normal intellect and life span – Normal mineralization of the skull • Mean adult higth 52” for men, 49” for women – No rib fractures • Orthopedic, orthodontic, neurologic sequelae • Diagnosis may not become obvious until 22–24 weeks
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Achondroplasia Achondroplasia
• Homozygous condition, lethal – manifests in abnormally short limbs earlier than the heterozygous form
Eleanor Simmonds celebrates after Peter Dinklage, the Emmy winning the gold medal in the and Golden Globe award Women's 100m Freestyle in Beijing winning actor
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Achondroplasia Proximal femoral diaphyseal-metaphyseal angle
• Chest normal • Normal angle • Disproportionally short limbs (rhizomelia) – 22 weeks: 98.5 ± 6.8° – Normal ossification – 32 weeks: 105.6 ± 7.3° – No fracture • Angle is increased in affected fetuses – No bowing or angulation • In 1 study, 5 of 6 affected fetuses had angle > 130° – Upper extremity more affected than lower • Cranium / Face – Enlarged head Most consistent finding other – Frontal bossing than long bone shortening – Depressed nasal bridge
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
15 3/6/2017
Achondroplasia Achondroplasia
Short Digits
“Trident Hand”
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Osteogenesis Imperfecta Osteogenesis Imperfecta
• Genetically heterogeneous group of disorders • The age & severity of skeletal malformation presenting with fragility of bones, blue sclerae, differ among the various types of osteogenesis loose joints and growth deficiency imperfecta • Advanced paternal age is a risk factor for OI – Type I – Type II – Type III – Type IV
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Osteogenesis Imperfecta Osteogenesis Imperfecta
• Type I • Type II – Most common – Lethal disorder – Autosomal dominant condition – Birth prevalence of about 1 in 60,000 – Severe bone shortening and bowing due to multiple fractures affecting – Birth prevalence of about 1 in 30,000 all long bones and ribs – 2nd & 3rd trimester ultrasound may demonstrate fractures of – Poor mineralization of the skull long bones – Limited limb movement – Skeletal hypoechogenicity & limb bowing are frequently not detected until after 24 weeks – Blue sclera – Progressive deafness, but life expectancy is normal
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
16 3/6/2017
Osteogenesis Imperfecta Type II Osteogenesis Imperfecta Type II
Severe bone shortening & angulation due to multiple fractures Severe bone shortening & angulation due to multiple fractures Narrowly spaced ribs
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Osteogenesis Imperfecta Type II Osteogenesis Imperfecta Type II
Severe bone shortening & angulation due to multiple fractures Severe bone shortening & angulation due to multiple fractures Narrowly spaced ribs Narrowly spaced ribs “Beaded” ribs and “wrinkled” bones due to multiple fractures “Beaded” ribs and “wrinkled” bones due to multiple fractures Concave, bell-shaped chest due to rib fractures
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Osteogenesis Imperfecta Type II
Severe bone shortening & angulation due to multiple fractures Narrowly spaced ribs “Beaded” ribs and “wrinkled” bones due to multiple fractures Concave, bell-shaped chest due to rib fractures Hypomineralization of the cranium Compression of skull by transducer
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
17 3/6/2017
Osteogenesis Imperfecta Type III Osteogenesis Imperfecta Type III
• Nonlethal, autosomal recessive , rare • Bowed femur • Progressively deforming condition • Multiple fracture represented by discontinuities • Long bone shortening & deformity may not in the femur become apparent until 19-22 weeks gestation • Decreased ossification – no posterior shadowing • Multiple fractures present at birth • Scoliosis, very short stature, progressive deformities from birth to adolescence
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Osteogenesis Imperfecta Type 1V Hypophosphatasia
• Mildest presentation of OI • Lethal, auto recessive condition • Autosomal dominant condition • Birth prevalence of about 1 in 100,000 • Not detectable on prenatal US • Severe shortening of the long bones • Premature ostoeporosis in 40’s & 50’s • Small thorax • No associated hearing impairment • Hypomineralization of the skull & long bones • Abnormal alkaline phosphatase assays • Polyhydramnios
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Hypophosphatasia Hypophosphatasia
• Poor mineralization • Demineralized segment where the vertebral bodies have a “ghost” outline and no acoustic shadowing
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
18 3/6/2017
Sirenomelia Hypophosphatasia Mermaid Syndrome
• SEVERE demineralization • Bones – Thin – Delicate – Absent • Hypoplastic ribs • Severe micromelia • A lethal congenital anomaly associated with gestational diabetes • Fractures not typical; • Partial to total sacral agenesis • Fusion of the lower extremities • thin bowed long bones • Bilateral renal agenesis (oligohydramnios, pulmonary hypoplasia)
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
Sirenomelia Resources
• Skeletal Dysplasia Registry – NIH funded • www.lpaonline.org • www.csm.edu/genetics/skeldys/nomenclature. html • www.TheFetus.net • Single femur and tibia at midline and a deformed foot • Iliac bones are abnormally located
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
• Cranium (shape, ossification) Fetal Musculoskeletal System • Facial profile • Spine • Bones – Severity & Type of Shortening Thank You – Morphology, Mineralization, Fractures • Chest (Thoracic / abdominal circumference ratio) • Polyhydramnios
Mani Montazemi, RDMS Mani Montazemi, RDMS Musculoskeletal Anomalies Musculoskeletal Anomalies
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