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Sonographic evaluation of msk dysplasia Dr. Muhammad Bin Zulfiqar

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Sonographic evaluation of msk dysplasia Dr. Muhammad Bin Zulfiqar

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In this presentation we will discuss the role of sonographic imaging in evaluation of MSK dysplasias especially Lethal dysplasia.
We can suggest which is not compatible with life.

In this presentation we will discuss the role of sonographic imaging in evaluation of MSK dysplasias especially Lethal dysplasia.
We can suggest which is not compatible with life.

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Sonographic evaluation of msk dysplasia Dr. Muhammad Bin Zulfiqar

  1. 1. Antenatal Ulrasound Evaluation of MSK Dysplasia DR. MUHAMMAD BIN ZULFIQAR PGR IV FCPS SERVICES INSTITUTE OF MEDICAL SCIENCES / HOSPITAL RADIOMBZ@GMAIL.COM Special Thanks to Sonoworld Team
  2. 2. Objectives • To Detect MSK Dysplasia • Characterize features of dysplasia • Classify MSK Dysplasia • To differentiate between lethal and non lethal dysplasia • To address lethal dysplasia
  3. 3. Terminology • Micromelia—Whole limb • Rhizomelia—Proximal • Mesomelia—mid bones • Acromelia—Distal
  4. 4. MSK Dysplaisa • More than 210 skeletal dysplasias are listed in The Gamut Index, among them: —19 are lethal or potentially lethal for the newborn. —50 are clinically apparent and identifiable at birth. —The prevalence of lethal skeletal dysplasia's is 0.9 per 10,000 births. The association of severe micromelia, small thorax and polyhydramnios were the initial clues to the diagnosis of a lethal skeletal dysplasia.
  5. 5. Types— Basis of Severity • Lethal • Non lethal
  6. 6. Non lethal • Most are non lethal • Heterozygous achondroplasia • Asphyxiating thoracic dysplasia • Chondroectodermal dysplasia • Chondrodysplasia punctata • Congenital spondyloepiphyseal dysplasia • Diastrophic dwarfism • Metatrophic dwarfism • Hypochondroplasia
  7. 7. Lethal dysplasia • Typically manifest before 24 weeks GA • Thanatophoric Dysplasia • Osteogenesis Imperfecta type II • Achondrogenesis type I and II • Jeune Syndrome • Homozygous achondroplasia • Congenital hypoposphatasia Continued
  8. 8. Lethal dysplasia • Chondrodysplasia punctata, (rhizomelic type) • Camptomelic dysplasia • Short rib polydactyly syndrome • Chondroectodermal dysplasia (usually nonlethal)
  9. 9. Danger Signs in Dysplaisa • Reduced Bone Density. • Marked Bowing • Fracture • Telephone handle bones • Narrow thorax • Micromelia > Rhizomelia • Cloverleaf skull • Frontal Bossing • Associated signs
  10. 10. Thanatophoric Dysplasia • Most common lethal skeletal dysplasia in neonatal period. • The name "thanatophoric" derives from the Greek meaning "death bearing" or "death bringing", • It is characterized by extreme rhizomelia, and a very narrow thorax, (which leads to respiratory distress and respiratory acidosis), normal trunk length, macrocephalia and polyhydramnios.
  11. 11. Thanatophoric Dysplasia • Two subtypes can be recognized by the presence or absence of curved femurs. 1) Thanatophoric dysplasia type 1, the most common subtype, characterized by curved and short femurs (shaped like a french telephone receiver), platyspondyly (35 per cent or less of the adjacent disk space in the lumbar spine). Very few type I cases have cloverleaf skull, and it is always mild. 2) Thanatophoric dysplasia type II, presenting longer and straighter femurs, taller vertebral bodies and almost always associated with severe cloverleaf skull.
  12. 12. DD • Achondroplasia—Mild limb shortening. • OI type II—Observation of the fractures. • Achondrogenesis—Extreme hypomineralization’ • Camptomelic dysplasia—Acute angulation of the mid shaft bowing of the long bones. • Trisomy 13 does not usually produce such short limbs.
  13. 13. Case 1—Thanatophoric Dysplasia • A 30 year old woman at 25-week gestation. Ana M. Bircher M.D., Fernando Heredia M.D., Philippe Jeanty M.D., Ph.D. 2002-09-25-11 Thanatophoric dysplasia © Bircher www.thefetus.net
  14. 14. Hydrocephalous
  15. 15. • The following coronal plane 3D reconstructions show the typical Kleeblattschädel or Cloverleaf skull.
  16. 16. • Transverse mid face plane clearly show exophtalmos, and the facial profile show frontal bossing and low nasal bridge.
  17. 17. • Frontal bossing • Flat nasal bridge • Exophthalmos
  18. 18. Note the "bell-shaped" thorax seen on the images below.
  19. 19. • The upper limbs were short, mostly rhizomelic and maintained a right angle throughout all examinations.
  20. 20. • Lower limbs were as well very short and rhizomelic. The femurs in these next images show the typical "telephone receiver" shape.
  21. 21. Post termination images
  22. 22. • Cloverleaf skull, short bones, narrow thorax
  23. 23. Case 2—Thanatophoric Dysplasia
  24. 24. • Right. Ultrasonogram demonstrates a cloverleaf-like skull. • Left. Rhizomelic micromelia with bowing of the humerus is apparent (arrows). The skin appears thick because of extreme redundancy.
  25. 25. The normal abdomen (arrows) is protuberant compared with the small thorax.
  26. 26. Postmortem radiograph shows generalized severe micromelia and a constricted thorax. Bowing is more apparent in the lower extremities.
  27. 27. Case 2—Thanatophoric Dysplasia • This is a 32-year-old woman, G5 P4 (4 previous normal pregnancies) at 33 weeks of pregnancy. The findings are: Severe hydrocephalus, Encephalocele, Low-set ears, Normal calcification of calvarium, Frontal bossing, Depressed nasal bridge, Exophtalmos, Short ribs, Narrow thorax, Severe rhizo- micromelia of limbs, Bowed bones polyhydramnios, Normal cardiac 4-chamber view and normal outflow tracts, Alberto Hernandez , MD 2004-02-11-07 Thanatophoric dysplasia, type II © Hernandez www.thefetus.net/
  28. 28. Narrow Thorax
  29. 29. • Severe Hydrocephalous
  30. 30. Images suggestive of encephalocele (artery seen on color Doppler, 3-D rendering)
  31. 31. • Low-set ears, • Normal calcification of calvarium, • Frontal bossing • Exophthalmos
  32. 32. • Short ribs • Narrow thorax
  33. 33. Severe Rhizo / Micromelia
  34. 34. • Bowed bones • Polyhydramnios
  35. 35. • Encephalocele with sphenoid defect
  36. 36. • Normal 4-chambers heart with normal outflow tracts • Fingers
  37. 37. Osteogenesis Imperfecta • Heterogeneous group of a generalized connective tissue disorder leading to micromelic dwarfism characterized by • Bone fragility • Blue sclera • Dentinogenesis imperfecta • This is a disorder of production, secretion, or function of Type I collagen, which is found in skin, ligaments, tendons, demineralized bone and dentine
  38. 38. Synonym of OI • Van der Hoeve syndrome, • Trias fragilitas osseum, • Eddowe"s syndrome, • Osteopsathyrosis ideopathica of Lobstein, • Ekman-Lobstein disease, • Osteogenesis imperfecta congenita, • Osteogenesis type III lethalis, • Brittle bone disease.
  39. 39. Osteogenesis Imperfecta • Four types • Type I—Autosomal dominant, most common, mild to moderate • Type II—Autosomal recessive, lethal form • Type III—Autosomal Recessive, progressively deforming, Compatible • Type IV—Autosomal dominant, mildest, best prognosi The placenta and amniotic fluid have been reported as normal
  40. 40. Elejalde et al Diagnostic Criteria for Lethal OI • An abnormally shaped skull, trapezoid, with varying shape when the mother coughed or laughed. • Decreased echoes of the long and trabecular bones. • Bell-shaped thorax, abnormal rib cage, and thin ribs with calluses. • Wide metaphyses and thin diaphyses causing an angulated shape with fractures and callus formation at all levels. • Decreased fetal movement with no flexion-extension of the upper and mostly lower limbs. No movements of the hands and feet. Continued Elejalde BR, de Elejalde MM. Prenatal diagnosis of perinatally lethal osteogenesis imperfecta. Am J Med Genet 14: 353-59, 1983
  41. 41. Elejalde et al Diagnostic Criteria for Lethal OI • Soles face each other and the legs are bowed in the middle of the tibia and fibula. There is angulation of all long bones. • Very decreased movement of the hips in an abnormal pattern with the lower limb moving only away/towards the midline with limited range of motion. No movement of the knee or ankle. • Long bone length less than normal for the gestational age. Elejalde BR, de Elejalde MM. Prenatal diagnosis of perinatally lethal osteogenesis imperfecta. Am J Med Genet 14: 353-59, 1983
  42. 42. Case 1 • A 21-year-old G4P3 with three normal children at 20 weeks estimated gestational age for evaluation of abnormalities found on routine ultrasound. Anne V. Hale*, MD, Effie Medford, MD, Luis A. Izquierdo, MD, Luis Curet, MD 1992-11-25-19 Osteogenesis imperfecta © Hale www.thefetus.net/
  43. 43. • Right. Poor ossification of skull bones which are easily compressible. Left. Transverse scan of the fetal thorax showing multiple fractured ribs.
  44. 44. Right. Stillborn showing evidence of micromelia. Left. Radiograph of the fetus showing fractured ribs and long bones (hypo mineralized).
  45. 45. Case 2 • A 22-year-old woman of a non-consanguineous marriage at 26-27 weeks old singleton intrauterine pregnancy with several abnormal findings. • This was her second pregnancy, and the first one ended as a miscarriage at 3rd month of the pregnancy. • Her family history was not contributive and she did not take any drugs during the pregnancy.
  46. 46. • Hypo mineralized compressible skull bones
  47. 47. • The images demonstrate narrow fetal thorax with short, irregular ribs.
  48. 48. • The images show short, bent femur of the fetus. Note that the both cortical layers of the femur are well recognizable (arrows on the left image ).
  49. 49. Short, bent bones of the upper extremity of the fetus.
  50. 50. • 3D images; Right image shows abnormal, beaded ribs. Left image 11 shows short upper limbs of the fetus.
  51. 51. • Right image shows short upper limb of the fetus; • Left image shows the fetal profile and face with partially opened eyes (not contributive to the diagnosis).
  52. 52. The images show appearance of the aborted fetus.
  53. 53. • X-ray images demonstrating the overall hypo mineralized skeleton with short, bent, irregular long bones, narrow bell-shaped thorax with abnormal ribs and extremely hypo mineralized skull.
  54. 54. Case 3—15 weeks Moshe Bronshtein, MD. 2014-11-24-21 Osteogenesis imperfecta type II © Bronshtein www.TheFetus.net
  55. 55. • Right— Hypo mineralized skull bones • Left— Hypo mineralized deformed ribs
  56. 56. • The images show fractures of all long bones (femur, tibia, radius), hypo mineralization of the bones (note that both cortical parts of the long bones are clearly visible).
  57. 57. Case 4—14 Weeks Moshe Bronshtein, MD. 2014-11-24-21 Osteogenesis imperfecta type II © Bronshtein www.TheFetus.net
  58. 58. • The images show fractures of the fetal femurs and blue sclera.
  59. 59. Achondrogenesis • Achondrogenesis is a skeletal dysplasia, which is characterized by • extremely shortened limbs, • normal to poorly ossified skull, • poorly ossified spine and pelvis, • severe pulmonary hypoplasia. • Type I and II have been distinguished based on clinical, radiologic, and histopathologic features..
  60. 60. Types • Type I: (Parenti Fraccaro Disease) • Defective enchondral and membranous ossification • Type II: (Langer Saldino Disease) • Defective enchondral ossification only
  61. 61. Prenatal diagnosis • Based on the extreme micromelia • Narrow thorax • Poor mineralization of the skull and vertebrae. • Polyhydramnios and a pseudohydropic appearance are also common. • When the demineralization affects the skull and iliac wings the presumptive diagnosis is Type I; • when the skull appears normally mineralized the presumptive diagnosis is Type II. •
  62. 62. Achondrogenesis Type I: Parenti-Fraccaro type Achondrogenesis Type II: Langer-Saldino type- Hypochondrogenesis • Extreme micromelia • Large head • Very short and thin ribs • Multiple ribs fractures (type IA) • Absent rib fractures (type IB) • Poor ossification of skull, spine, ischium, pubis, iliac bones • Prominent forehead, flat face, • Micrognathia • Absence of rib fractures • Normal calvarial ossification • Various degrees of ossification of: spine sacrum, ischial, pubic bones • Hypochondrogenesis: absence of ossification limited to the cervical and sacral vertebrae and pubic bones often a cleft palate
  63. 63. Case 1—Achondrogenesis I • This is a case of a lethal skeletal dysplasia diagnosed at 14 weeks of gestation. • Ultrasound examination showed increased nuchal translucency, severe micromelic shortening of all extremities, short, narrow thorax, protuberant abdomen. The vertebral bodies were not ossified. Calvarium was enlarged with bulging forehead and depressed nasal bridge. • Patient decided for the termination of the pregnancy. The final diagnosis based on the ultrasound findings and X-ray images was Achondrogenesis, type I.
  64. 64. • Right. Fetal head • Left. Narrow thorax with protuberant abdomen.
  65. 65. • Right. Image shows an increased nuchal translucency (image is not taken in the neutral position of the head). • Left Image shows radius and ulna.
  66. 66. • Right image shows humerus. • Left image shows femur. • Shortening of all long bones, less than 2nd percentile.
  67. 67. • Images show short, narrow thorax and protuberant abdomen.
  68. 68. • Fetus after the pregnancy termination, note shortening of upper and lower extremities.
  69. 69. • Profile of the fetus with depressed nasal bridge, bulging forehead and micrognathia.
  70. 70. • X-ray images of the fetus, note that vertebral bodies are non- ossified and skull is poorly mineralized.
  71. 71. Case 2 Achondrogenesis I A 22-YEAR-OLD, G1P0 WOMAN WAS REFERRED AT 21 WEEKS GESTATION FOR A PRENATAL ULTRASOUND THAT DEMONSTRATED SHORT LIMBS AND HYDROCEPHALUS. THE PATIENT AND HER HUSBAND WERE CONSANGUINEOUS
  72. 72. • View of the head: note the absent mineralization of the skull. • Severe micromelia was confirmed with a femur length of 13 mm
  73. 73. The femur is short and so poorly mineralized that both sides are visible. The chest was hypo plastic and the heart, which appeared to occupy the whole chest, compressed the lungs
  74. 74. • Absent mineralization of the spine and skull
  75. 75. • Absent mineralization of the spine and skull
  76. 76. Case 3 Achondrogenesis II A 26-YEAR-OLD PREGNANT WOMAN AT 26 WEEKS IN HER FIRST PREGNANCY DUE TO FETAL SHORT LIMBS
  77. 77. • Right. Dilated renal pelvis • Mid. Narrow thorax • Left. 3-D reconstruction of spine with short ribs
  78. 78. • Absent Sacrum • Scapula and humerus • The arm • Small lower limb
  79. 79. • Lower limb • Micrognathia
  80. 80. • Abnormal vertebral column with flat vertebral bodies and absent ossification in the sacral and upper cervical regions. • The thorax was small with short ribs. • The long tubular bones were shortened without metaphyseal spiking. • The widened metaphyseal regions gave the humerus a dumbbell appearance. • The pelvis was characterized by an absence of ossification of the pubis, hypoplastic iliac wings and flat acetabular roofs
  81. 81. Case 4 Achondrogenesis II A 25-YEAR-OLD WOMAN (G3P2), WITH NON-CONTRIBUTIVE FAMILY HISTORY AND NEGATIVE EXPOSURE TO TERATOGENS, AT 11 WEEKS OF PREGNANCY DUE TO DETECTION OF FETAL ANOMALIES.
  82. 82. • Images show increased nuchal translucency and enlarged skull with flat nasal bridge of the fetus.
  83. 83. • Images show anasarca of the fetus and severe micromelia
  84. 84. Polydactyly
  85. 85. Severe micromelia.
  86. 86. • Ventricular septal defect of the heart. • Enlarged fetal skull and increased nuchal translucency
  87. 87. • Narrow thorax • Poorly mineralized vertebra • Poorly developed pelvic bones • Severe micromelia • Enlarged skull
  88. 88. Asphyxiating Thoracic Dysplasia (Jeune Disease) • A rare autosomal recessive skeletal disorder characterized by a • small thorax; • brachymelia, predominantly of the rhizomelic type; • pelvic abnormalities (hypoplastic iliac wing), and • renal anomalies. • It has a variable phenotypic expression.
  89. 89. Asphyxiating Thoracic Dysplasia (Jeune Disease) • Flat, narrow chest (bell-shaped), • with short, horizontal ribs • associated with short limbs and brachydactyly seem to be the main features. • The ribs do not reach more than halfway around the thorax. • usually rhizomelic; square-shaped iliac wings. • The long bone shortening might not become sonographic apparent until 24-26 weeks of gestational age.
  90. 90. • The fairly normal limbs length (note the angulation of the femur and humerus).
  91. 91. • Short ribs causing a small narrow thorax
  92. 92. • Short ribs causing a small narrow thorax
  93. 93. Normal ribs Cord Cyst
  94. 94. Narrow Chest
  95. 95. Case 2 Asphyxiating Thoracic Dysplasia LONGITUDINAL VIEW OF THE CHEST AND ABDOMEN OF A FETUS WITH ASPHYXIATING THORACIC DYSPLASIA. NOTE THE CONSTRICTION OF THE CHEST
  96. 96. Hypophosphatasia • Autosomal recessive anomaly due to defective bone mineralization and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase • Three Subtypes • Lethal type 1 with prenatal manifestations of short demineralized long bones, craniosynostosis and neonatal hypercalcemia; a • Type 2 with rickets-like skeletal changes, fractures and premature loss of teeth; and • Type 3 with only metabolic anomalies detected on biochemical screening.
  97. 97. Case— Hypophosphatasia PATIENT AT 16 WEEKS GESTATION
  98. 98. • Right image shows hypoechoic skull and short humerus next to it. • Left image shows short femurs of the fetus.
  99. 99. • Sagittal views of the fetus - hypoechoic skull and short long bones and narrow thorax can be seen.
  100. 100. • Images show short femurs and lower extremities of the fetus.
  101. 101. After expulsion
  102. 102. Chondroectodermal Dysplasia—Ellis Van Crevald Syndrome • Autosomal recessive acromesomelic dwarfism—Mesodermal Dysplasia • Associated with congenital heart disease
  103. 103. Case 1— Chondroectodermal Dysplasia 30 WEEKS GESTATION
  104. 104. • Right image shows a transverse scan of the fetal head at 24 weeks with brachycephalic configuration (BPD 90 mm, which corresponds to 36w6d of gestational age). • Left image was taken at 30 weeks of pregnancy and shows the fetal humerus measuring 39.6 mm, which corresponds only to 24w1d of gestational age (rhizomelia).
  105. 105. • 30 weeks; the right image shows the fetal ulna measuring 42.1 mm, which corresponds approximately to 27-28 weeks of pregnancy. The left image shows the fetal femur measuring 40.3 mm, corresponding only to 23 weeks of pregnancy (rhizomelia).
  106. 106. • 30 weeks; Right image shows the fetal tibia measuring 40.9 mm, corresponding approximately to 26-27 weeks. Left image shows postaxial polydactyly of the fetal hand.
  107. 107. Narrow thorax of fetus
  108. 108. • 30 weeks; the right image shows a transverse scan of the fetal abdomen - no anomaly is seen. • The mid image shows a transverse scan of the fetal thorax at the level of the four-chamber view of the heart. The narrow thorax causes a relative cardiomegaly of the heart. Atrioventricular septal defect was also present. • Fetal gender (male).
  109. 109. • Narrow Thorax • Postaxial Polydactyly
  110. 110. Case 2— Chondroectodermal Dysplasia
  111. 111. • Coronal views showing a normal thoracic relative to the size of the abdomen and head.
  112. 112. • Postaxial polydactyly with the extra-digits each containing two small bony phalanges was visualized in both hands and feet.
  113. 113. Mild Pyelectasis Profile face
  114. 114. All long bones are short
  115. 115. Chondrodysplasia Punctata Definition: Erratic cartilage calcification during growth which produces the heterogeneous group of disorders that results in small ossification centers in the epiphyseal cartilage of the long bones and spine, skin lesions, cataracts, craniofacial dysmorphism, joint contractures1,3 , and cardiac malformation. In surviving children, abnormal growth leads to dysmorphism, kyphoscoliosis, limb shortness, and luxation of the hip1,3,5 .
  116. 116. Classification • Autosomal dominant type (non rhizomelic) • Autosomal recessive type (rhizomelic) • X- linked dominant type • X- linked recessive type • Sheffield, mild type
  117. 117. AR Chondrodysplasia Punctata Potential sonographic findings: •Skeletal: mild punctuate (stippled) calcific deposits in cartilaginous axial skeleton; symmetric rhizomelic short limb dwarfism; joint contractures; foot deformities; bowing of proximal limbs. •Craniofacial: flat face; microcephaly; micrognathia; cataracts; cleft palate. •Cutaneous abnormalities: ichthyosis. •Congenital heart disease. Radiologic findings: •Symmetric shortening of the proximal bones. •Punctate calcific deposits in infantile cartilaginous skeleton. •Coronal clefts in the vertebra.
  118. 118. 00 Type Potential prenatal findings Autosomal dominant Asymmetric mild shortening of humerus and femur, vertebral body deformities and scoliosis, stippling epiphyses of the proximal humerus, bowing, flection contracture of the joints, clubfoot, asymmetric head, frontal bossing, flat nasal bridge, hypertelorism, cataracts, microophthalmia. Autosomal recessive Stippled axial skeleton, symmetric rhizomelic short limbs, joint contractures, foot deformities, bowing of the proximal limbs, flat face, microcephaly, micrognathia, cataracts, cleft palate. X- linked dominant Flat nasal bridge, frontal bossing, asymmetric shortening of the limbs, flexion contractures, foot deformities, and scoliosis, polydactyly. X- linked recessive Asymmetric mild shortening of the limbs, diffuse bone stippling, nasal hypoplasia, cataracts, hypoplasia of the distal phalanges. Sheffield, mild type Flattened tip of the nose, depressed nasal bridge, stippling of calcaneus bones.
  119. 119. Case— Chondrodysplasia Punctata A 30-YEAR-OLD WOMAN G5, P4 PRESENTED FOR A ROUTINE ULTRASOUND SCAN. HER OBSTETRIC HISTORY WAS SIGNIFICANT FOR A POSTNATAL FETAL LOSS AT 5 MONTHS OF AGE DUE TO UNKNOWN METABOLIC ILLNESS OF THE FETUS.
  120. 120. • Long bones:
  121. 121. • Profile view of the face: A flat mid-face is seen. • 2-D and 3-D scans of the femur: Punctate epiphyseal calcifications as marked are seen.
  122. 122. • Images of the fetal spine: Punctations are seen. • 3-D and 2-D views of the face at 32 weeks of gestation:
  123. 123. • 3-D and 2-D views of the face at 32 weeks of gestation:
  124. 124. • View of the right eye at 32 weeks: A cataract can be seen. • View of the femur at 34 weeks of gestation
  125. 125. Case—2 Chondrodysplasia Punctata
  126. 126. • The head shows poor mineralization (note that the proximal hemisphere is visible): • Profile view of the face. The left image demonstrates the binocular distance. Flat mid-face is seen (note the small/absent nasal bone). •
  127. 127. • 3-D view showing the flat saddle of the nose: • A normal 4-chamber view and abdomen: •
  128. 128. • The left and right humerus. Note the hypomineralization seen as a bone that allows ultrasound to penetrate it:
  129. 129. Ulna, tibia and left femur:
  130. 130. Fibula and right ulna: •
  131. 131. • Leg and femur
  132. 132. • View of the hand: • View of the left leg and rocker bottom foot.
  133. 133. • View of the right foot between placenta and uterus. • Images of fetal spine
  134. 134. Camptomelic Dysplasia • Sporadic / Autosomal recessive • Campomelic dysplasia is a congenital disorder characterized by development of abnormal curvature of the long bones, particularly from lower extremities, such as femur and tibia. Severe angulation may mimic fracture. • Types • Long limbed • Short limbed Synonyms: Camptomelic dysplasia, campomelic syndrome, campomelic dwarfism, congenital bowing of the limbs
  135. 135. Camptomelic Dysplasia •Associated with • Hydrocephalus (23%) • Congenital heart disease (30%): VSD, ASD, tetralogy, AS • Hydronephrosis (30%) • OB-US • Bowing of tibia+ femur • Decreased thoracic circumference • Hypo plastic scapulae • Cleft palate
  136. 136. Case 1— Camptomelic Dysplasia
  137. 137. • Bowing of the ulna. • Note the gentle curve that sometimes differentiate these from the more acute angles of the osteogenesis imperfecta fetuses.
  138. 138. Bowing of femur
  139. 139. Case 2— Camptomelic Dysplasia THIS IS A CASE OF A 33-YEAR-OLD G5 P4 WITH NON-CONTRIBUTIVE FAMILY OR PERSONAL HISTORY AT 22 WEEKS OF GESTATION. THE FATHER OF THE BABY WAS A FIRST DEGREE CONSANGUINEOUS. THE PREVIOUS PREGNANCIES WERE UNCOMPLICATED AND ALL THE CHILDREN WERE HEALTHY.
  140. 140. • 22 weeks, Right. image shows femur, Left image shows tibia, fibula and foot. Femur measured 3 weeks less than BPD.
  141. 141. • Right. image shows bowed long bones. • Left image shows cervical spine with prominent lordosis.
  142. 142. • Right image shows clubfoot. • Left image shows upper extremities with shortened and bowed long bones.
  143. 143. • Right image shows cervical hyperlordosis. • Left image shows small chest and prominent abdomen.
  144. 144. • Right image shows the axial view of the head with BPD. • Left. image shows a bowed femur, FL lags 7 weeks behind BPD and bowing with fine curvature.
  145. 145. • Polyhydramnios • Pyelectasis
  146. 146. • Image shows bowed, shortened lower extremity with clubfoot and foot hyperextension, arrow indicates the typical skin dimple.
  147. 147. • 3-D images, Club feet and low set ears and depressed nasal bridge.
  148. 148. • Right. Image shows the skin dimples. • Left Image shows shortened, bowed extremities, note short, small chest.
  149. 149. • X-rays, Right. image shows prominent occiput and cervical hyperlordosis. Left Image shows small, barrel- shaped chest, short upper extremities.
  150. 150. Case 3— Camptomelic Dysplasia A 25-YEAR-OLD WOMAN G2P1 AT 18 WEEKS THAT REVEALED A DISCREPANCY IN THE FETAL MEASUREMENTS. THE GESTATIONALAGE DERIVED FROM THE HEAD MEASUREMENT WAS 19 WEEKS, BUT IT WAS ONLY 14 WEEKS WHEN DERIVED FROM THE LONG BONE MEASUREMENTS. THE ANAMNESIS OF THE PATIENT WAS UNREMARKABLE EXCEPT FOR A COMMON COLD AT THE BEGINNING OF PREGNANCY WITHOUT TEMPERATURE. Anamnesis definition, the recollection or remembrance of the past;
  151. 151. Bowing of femur, tibia, ulna
  152. 152. Ulna, radius and humerus
  153. 153. • Bowed short bones, narrow thorax seen.
  154. 154. • Radiograph with bell-shaped thorax, mild bilateral lunar bowing, shortening and bowing of the whole bones of lower extremities and hypo plastic scapulae.
  155. 155. Short rib polydactyly syndromes Short rib polydactyly syndromes are lethal forms of skeletal dysplasia, characterized by thoracic hypoplasia, polydactyly and shortening of the long bones. Three types of the disorder were described:  Type I: described by Saldino and Noonan in 1972  Type II: described by Majewski in 1971  Type III: described by Naumoff in 1977 Clinical, radiographic and morphologic studies suggest that types I and III just represent phenotypic variations of the same disorder.
  156. 156. Diagnosis • Diagnosis: Prenatal diagnosis by ultrasound can be accomplished by finding the characteristic triad which includes micromelic dwarfism, short and horizontal ribs with narrow thorax (what leads to hypoplasia of the lungs), and polydactyly.
  157. 157. Type 1—(Saldino-Noonan): • Short stature, Postaxial polydactyly of hands and/or feet, syndactyly, underossified phalanges, Notch-like ossification defect of vertebral bodies, small iliac bones, triangular ossification defects above the acetabulum. Cardiac, gastrointestinal, and urogenital malformations can also be found. Occasionally preaxial polydactyly and sex-reversal (46,XY with female phenotype) can occur[
  158. 158. Type II (Majewski): • Short stature with extremely short limbs, midline cleft lip, cleft palate, short flat nose, low set and malformed ears, preaxial and postaxial polysyndactyly of hands and feet, premature ossification of proximal epiphyses of femur, humerus and lateral cuboids, underossified phalanges, high clavicles, and ambiguous genitalia. Less frequently, hydrops and polyhydramnios can also be found.
  159. 159. Differential Diagnosis • Thanatophoric dwarfism, • Chondrodysplasia punctata, • Osteogenesis imperfecta, • Camptomelic dysplasia[7] • Oro-facial-digital syndrome type II Prognosis: SPRS are lethal conditions. Affected neonates usually die few hours after birth from respiratory insufficiency, due to severe pulmonary hypoplasia5, 6. Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not changed when continuing the pregnancy is opted. Confirmation of diagnosis after birth is important for genetic counseling.
  160. 160. CASE 1— Short Rib Polydactyly Syndrome A PRIMIGRAVIDA WITH A FIRST DEGREE CONSANGUINEOUS MARRIAGE AT 22 WEEKS OF GESTATION.
  161. 161. • Markedly short ribs • Polydactyly
  162. 162. • Right image shows abdominal circumference corresponding with 17 weeks of gestation, note short ribs. • Left Image shows a forearm with shortened ulna and radius.
  163. 163. • Short ribs
  164. 164. • Sagittal view of the shortened and thickened ribs • Foot with sandal gap and polydactyly. • Foot with shortened tibia and fibula and hand with polydactyly.
  165. 165. • 3D-images showing shortened upper extremities, narrow thorax, prominent forehead.
  166. 166. • Images showing short ribs, shortened and curved humeri and forearms, genu recurvatum.
  167. 167. • Images of the fetus with postaxial polydactyly, genu recurvatum, narrow, short thorax. Face shows abnormal features, prominent forehead, broad, depressed nasal bridge and protruding tongue.
  168. 168. CASE 1— Short Rib Polydactyly Syndrome THIS IS A 22-YEAR-OLD WOMAN (G4, P2) WITH UNREMARKABLE FAMILIAR HISTORY, AT 29 WEEKS OF GESTATION DUE TO A FETAL ASCITES.
  169. 169. • Shortened femur (left); and ulna (right).
  170. 170. • Shortened tibia (left); and polydactyly of the hand (right).
  171. 171. • Narrow Thorax
  172. 172. • Fetal Ascites • Transverse plane through thorax
  173. 173. • Coronal plane through normal fetal lips and nose (left); • Coronal plane through the fetal skull - normal (right).
  174. 174. • sagittal cranial plane - normal (left); • Axial plane through the posterior fossa of the skull - normal cerebellum with transcerebellar diameter concordant with gestational age (right).
  175. 175. • Postnatal radiograms - bicycle handle like clavicles (left); • Micromelia with dominant rhizomelia (right).
  176. 176. Achondroplasia • Misnomer—More accurate term is Chondrodysplasia. • Rhizomelic micromelia associated with frontal bossing and low nasal bridge • Two types: • Heterozygous—Non lethal • Homozygous—Lethal
  177. 177. Heterozygous Achondroplasia • Prototype of rhizomelic dwarfism • Autosomal dominant / sporadic (80%) disease with quantitatively defective endochondral bone formation • Related to advanced paternal age; epiphyseal maturation +ossification unaffected
  178. 178. Homozygous Achondroplasia • Hereditary AD disease with severe features of achondroplasia (disproportionate limb shortening, more marked proximally than distally) • Large cranium with short base + small face • Flattened nose bridge • Short ribs with flared ends • Hypoplastic vertebral bodies • Decreased interpedicular distance • Short squared innominate bones, Flattened acetabular roof, Small sciatic notch, Short limb bones with flared metaphysis , Short, broad, widely spaced tubular bones of hand
  179. 179. DD between Achondroplasia • At 26 weeks BPD age: • Homozygous fetuses never had a femoral length that exceeded 34 mm. (progressive decrease in relative femoral length in the second trimester) • Heterozygous fetuses always had a femoral length that exceeded 34 mm. • Fetal femoral growth curves therefore allows the distinction between homozygous, heterozygous and unaffected fetus in the second trimester.
  180. 180. • Right. US scan of a homozygous achondroplastic fetus at 17.0 weeks gestational age shows a morphologically normal femur (cursors). • Left. US scan of a different homozygous achondroplastic fetus at 34.0 weeks gestational age shows an obviously short and thick femur with metaphyseal flaring (cursors).
  181. 181. • Short ribs with flared ends, hypoplastic vertebral bodies (platyspondyly), flat acetabular roof and small sciatic notches favor Homozygous Achondroplasia
  182. 182. Type Skull Thorax Limb Spine Pelvis Achondrogenesis Type IA (Houston-Harris) poorly ossified short, round chest with multiple rib fractures very short, broad tibiae & fibulae, wedge-like femora with proximal metaphyseal spike unossified vertebral bodies hypoplastic arch-like iliac bones with short vertical ischia Achondrogenesis Type IB (Fraccaro), poorly ossified short chest with thin ribs, cupped ends, no fractures very short with trapeziod femora, crenated tibiae, unossified fibulae unossified vertebral bodies hypoplastic crenated iliae Achondrogenesis Type II (Langer-Saldino) large calvarium with posterior ossification defect barrel-shaped, with short ribs very short with mild-moderate metaphyseal changes, long fibulae thoracolumbar ossification short iliae, flat acetabular roots, unossified pubic bones, ossified ischia
  183. 183. Type Skull Thorax Limb Spine Pelvis Kniest dysplasia frontal flattening, maxillary hypoplasia, shallow orbits short ribs club-like metaphyses, delayed ossification of femoral heads diffuse flattening, coronal clefts small ilia, increased acetabular angles with irregular edges Thanatophoric dwarfism frontal bossing+ clover- leaf skull narrow, pear- shaped, short, bowed, with metaphyseal flaring normal ossification small sacrosciatic notches, spiculated acetabulum Osteogenesis Imperfecta, Type II soft and membranous flail chest at birth short fracture liability normal
  184. 184. Type Skull Thorax Limb Spine Pelvis Achondroplasia megalocephaly slight rib flaring rhizomelic, with leg bowing, trident hands thoracolumbar kyphosis, lordosis short iliac wings Hypochondropla sia Normal Normal short vertebral canal narrowed Normal Spondyloepiphy seal dysplasia Normal short barrel chest, + pectus carinatum mild rhizomelic shortening with bowing severe kyphoscoliosis retarded ossification of pubic bones
  185. 185. Type Skull Thorax Limb Spine Pelvis Asphyxiating thoracic dysplasia Normal narrow, long, short anteriorly cupped ribs + post-axial polydactyly, variably short normal square, short iliae, flat acetabulae Hypophosphatasia Thin and membranous markedly reduced ossification, short short with bowing, long bones are frayed poor ossification with hypoplastic vertebrae normal
  186. 186. Take Home Message • Antenatal Sonography can differentiate between lethal / non lethal dysplasia. • Can differentiate between different lethal Dysplasia. • Can suggest compatibility of life antenatally.
  187. 187. Thank you

Editor's Notes

  • Common findings Type I 19, 23 Severe micromelia. Predominantly rhizomelic reduction of limbs. The limb bones are under the 3rd centile. These are also curved (particularly the femur), with a telephone receiver like shape( due to broadening of the metaphyseal ends). Also the fibulae appears shorter than the tibiae. Narrow and small chest, "bell-shaped" or "pear-shaped". This can be suspected easily when the cardiac circumference is greater than 60 % of the thoracic circumference. Also, the abdomen appears protuberant in comparison with the chest.  Platyspondyly.
    Type II 19, 29, 23
    Cloverleaf shaped skull, with a trilobed appearance in coronal views (kleeblattschädel)30. These three lobes are represented by the prominent vertex of the calvarium in the middle and the two temporal bones on the sides.31This is caused by the extreme wideness of the frontal suture, that becomes wider superiorly, being then contiguous to a huge anterior fontanel.7 Synostosis occur along the sagittal and lambdoid sutures in such way that the sagittal suture is displaced posteriorly. The posterior fontanel is usually opened. Some authors consider the cloverleaf skull as the end point of all the craniosynostosis syndromes, if complete craniosynostosis of all the sutures is present.33 There are three explanations for the primary cause of the cloverleaf shape of he skull.
    1.- a premature closure of the sutures.
    2.- the promontory growth of a relatively normal cartilage-bone tissues at the skull base, resulting in an early synostosis and consecutive fusion of the cranial sutures.7, 32 .
    3.- the primary developmental disorder in the brain, with secondary deformation of the bones.7
    Severe micromelia. Limb bones under 3rd centile. Curved and short bones, although the femurs are straighter than in type I Platyspondyly, with vertebral bodies taller than in type I. Narrow thorax, with small ribs. Low-set dysmorphic ears20

  • Central nervous system: megalencephaly, hydrocephaly.
    Craniofacial: small foramen magnum and short skull base, frontal bossing, low nasal bridge, bulging eyes, small facies.
    Limbs: abducted and externally rotated, (this can be due to the redundancy of the skin, that appears thick, preventing normal movements, and orienting the limbs in right angles compared with the body).22  Scapulae are small and squarish. Hands are very short with sausage-like fingers. Simian crease can also appear.
    Polyhydramnios
  • Although the conjunction of a 2 D ultrasound with 3 D ultrasound using multiplanar and 3 D rendered images can reliably detect thanatophoric dysplasia, in some special cases it is very hard to reach an accurate diagnosis. These include those small fetuses with thanatophoric dysplasia type I with an onset before 20 weeks of gestational age20, 34 In those cases, only the molecular genetic analysis  from either cultured amniotic fluid cells, cord blood or fetal tissue can provide the definitive diagnosis.20, 26 The most important differential diagnosis is with achondroplasia, because it is the most frequent of the life-compatible short-limb skeletal dysplasia . The distinction is quantitative, with patients with achondroplasia having milder phenotypes than thanatophoric dysplasia. Shortening of femoral length is the best parameter when stablishing a differential diagnosis.35 Mild shortening (greater than 80 % of the mean for gestational age) is often seen in achondroplasia, while severe shortening (30 to 60 %) is present in thanatophoric dysplasia . However, there is some overlap between these two malformations. Other severe osteochondrodysplasias include achondrogenesis and osteogenesis imperfecta type II, although most of them are lethal. Observation of the fractures can suggest the diagnosis of OI type II, and extreme hypomineralization make the diagnosis of achondrogenesis. The femur length / abdominal circumference ratio is useful for predicting a lethal fetal outcome when a skeletal dysplasia is diagnosed.36 Other differential diagnosys are Camptomelic dysplasia and trisomy 13. The first can be ruled out by the acute angulation of the midshaft bowing of the long bones. Trisomy 13 does not usually produce such short limbs.
    Prognosis By definition, this malformation is uniformly lethal before or shortly after birth. The main cause for this is lung hypoplasia (due to the small thorax) which lead to immediate postnatal asphyxia
  • Type I
    This is the classic, non-lethal type with autosomal dominant inheritance. It is the most common type. The patients usually have blue sclerae, and the infants lack fractures at birth and are of normal height. Type 1A has abnormal dentinogenesis and type 1B does not. Vertebral malalignment and deformation of tubular bones would be unusual in this type. 96% are able to walk, and 35 % are deaf, with the usual onset in childhood or puberty. The recurrence risk is 50%.
    Type II
    Stillbirth or neonatal death is certain, making this a much more severe form of the disease with many fractures occurring from movement in utero and at birth. Limb shortening with crumpled long bones with bowing is usually present. Broad, beaded ribs are present except in types IIB & IIC. Type IIA is due to a new autosomal dominant inheritance, so recurrence risk is 2-5%. In the earlier literature, the risk was thought to be 25%, due to autosomal recessive inheritance, but subsequent studies have found a paucity of affected siblings9,14,15,16 of probands and an increased paternal age effect. A small thorax is seen with poor ossification of the skull and blue sclerae. Many of the fetuses will be small for gestational age. Types IIB & IIC contain recessively inherited forms, and the recurrence risk is 10-25%.
    Type III
    This type is characterized by progressive deformity of the long bones and spine and often leads to an early death. These patients may show shortened and bowed long bones and decreased ossification of the skull. The blue sclerae may fade or disappear later in life. It is hard to differentiate from type II at birth when these also have multiple fractures present. Autosomal dominant and recessive inheritance is seen, with a recurrence rate quoted at 7%.
    Type IV
    This is the mildest form and may not be separate from Type I. Inheritance is autosomal dominant and their sclerae can fade to white over time. Fractures and deformities are rare. The recurrence risk is 50%.
    In 198817, Hobbins in examined 66 females at risk for skeletal dysplasia, and osteogenesis imperfecta was diagnosed in one with decreased long bone measurements and a femoral fracture. He found no false positives and concluded that skeletal dysplasias can be recognized by ultrasound in the second trimester if one compares the measurements of the long bones with normal dimensions.
  • In addition, the following criteria seemed to be consistent with current diagnosis of osteogenesis imperfecta5-7,9,12,18-20:
    ·        Bowing of the long bones may be seen in normal fetuses, but campomelia or excessive bowing is more suggestive of campomelic dysplasia and osteogenesis imperfecta. Muñoz et al. found that six out of eight patients had multiple fractures, demineralization of the calvaria, and femoral length greater than three standard deviations below the mean for gestational age12. There were no false positives with this criteria, but two patients were undiagnosed. They also felt that a normal scan after 17 weeks excluded Type II.
    ·        BPD is normal and the abdomen is normal or small for gestational age. However, the abnormal compressibility of the vault may alter the measurements of the BPD.
    ·        Angulation and fractures are apparent, resulting in foreshortening of the long bones. The cortex will appear wrinkled with thickening secondary to callous formation.
    ·        Types IIB, IIC, & III need a longer observation time.
    ·        Demineralization of the calvaria with decreased or absent brightly echogenic margins and enhancement of the brain are seen. The major sutures may also appear abnormally open.
    ·        Increased visibility of the orbits and arterial pulsations are seen.
    ·        Increased through transmission is seen with the spine, ribs, sphenoid, mandible, ethmoid, clavicles, iliac bones and long bones due to decreased mineralization.
    ·        A small, bell-shaped thorax is seen due to collapse of the rib cage.
    ·        Abnormal ventricle to hemisphere ratios and decreased fetal movement may be part of the presentation.
    ·        Beaded ribs are possible, but are not always present.
    ·        One may see the typically peculiar face as pictured before in this article, especially with type II.
    ·        Range of motion of the elbow and wrist is decreased with no movement at the knee and ankle, and no extension or flexion of the limbs was seen in type II. Overall decreased movement is usually apparent.
    ·        The soles of the feet face each other and the limbs make a square. The lower limbs are internally angulated, and all the long bones are deformed in type II.
    ·        The placenta and amniotic fluid have been reported as normal.
  • The classification is based on radiographic and histopathologic criteria. The disorganization of the chondrocytes in the growth plate results in absence of matrix formation of cartilage, which may be caused by lack of production of type II collagen11,12.
    Type IA (Houston-Harris)
    Achondrogenesis type IA is characterized by minimal ossification of the skeleton. This subtype also includes cases that exhibit both, defective ossification of endochondral and intramembranous bone. Therefore, the skull is poorly ossified. There is no ossification of the vertebral bodies, and the iliac bones appear crenate. The ribs have cupped metaphyses and multiple fractures are seen1. Histologically, the cartilage appears hypercellular with chondrocytes clustered in a monochromatic matrix. These chondrocytes contain large round, or oval inclusions and the lacunae are dilated11,12.
    The epiphyseal cartilage contains many vascular channels, which are also dilated. The growth plate demonstrates disorganized endochondral ossification with lack of columnization in the proliferative and hypertrophic zones.
    The metaphyseal cupping seen on radiographs results from the membranous subperiosteal ossification as it expands along the growth plate11,12.
    Type IB (Fraccaro)
    Type IB (Fraccaro) is differentiated from subtype IA by cranial vault ossification and the absence of rib fractures. Generally, the long bones are shorter than those seen in type IA1. Histologically, this form is differentiated form type IA by more random dispersement of the chondrocytes in the epiphyseal cartilage. Also, the inclusions are absent, but the cytoplasm appears vacuolated. There is no dilation of the lacunae and the matrix is condensed, forming rings around the chondrocytes11,12.
    Type II (Langer-Saldino)
    Type II (Langer-Saldino) has a more variable presentation, generally characterized by a small barrel-shaped thorax, no rib fractures and halberd-shaped iliac bones. Borochowitz has suggested that achondrogenesis type II and hypochondrogenesis are phenotypic variations of the same disorder, with hypochondrogenesis representing the milder forms of achondrogenesis type II1. On histology, this severe form contains immature chondrocytes with large, ballooned lacunae, and a diminished intracellular matrix. The growth plate is very disorganized and lacks columnization. There are abundant stellate vascular channels and perivascular fibrosis in the epiphyseal cartilage11,12.
  • Prototypes I-IV
    Whitley and Gorlin4 have also characterized achondrogenesis into prototypes I through IV. Prototype I combine traits of IA and IB, to include rib fractures and the most severe limb shortening. Prototypes II through IV represent cases without rib fractures, those with further development of the long bones, and further ossification of the vertebral bodies. Prototype IV, therefore, represented previous cases classified as hypochondrogenesis. These prototypes are based on radiographic measurement of the Femoral Cylinder index (length of femur/width at mid-shaft), which is a measure of endochondral growth4.
  • When demineralization is present by ultrasound, X-ray will confirm it. .
    However, the absence of demineralization by ultrasound cannot be used to presume a radiological demineralization. Since the recognition of demineralization by ultrasound is fraught with false negatives, there will be a tendency to over report the Type II form.
  • Jeune syndrome (first described by Jeune et al.[1] in 1955), Jeune Thoracic Dystrophy, Thoracic-Pelvic-Phalangeal Dystrophy.
  •   Polydactyly is an inconstant feature of Jeune syndrome (approximately 14%)[7]. If present, usually asymmetric and the feet are also affected[8].
    ·         Thoracopelvic dysplasia should be considered when a low thoracic circumference and abdominal circumference ratio (<0.8) is observed[9].
    ·         Absence of fetal respiratory movement.
    ·         The main visceral abnormality is cystic dysplastic renal disease, which is progressive and not usually apparent before birth, althought association with oligohydramnios has been described3. If renal dysplasic disease is not found, polyhydramnios can appear.
    ·         Jeune should be thought of prospectively among the numerous cases of increased nuchal translucency with normal standard karyotype.
    ·         Associated anomalies are numerous as described later.
    ·         Prenatal diagnosis has been reported as early as 16 - 18 weeks of gestational age especially in cases of family history2,7.
    Case:
  • Ellis-van Creveld syndrome (chondro-ectodermal dysplasia):
    Autosomal recessive (short arm of chromosome 4) skeletal dysplasia;
    ·         Characterized by short limbs, short ribs, postaxial polydactyly of the hands (feet are uncommonly affected8), dysplastic nails and teeth, peculiar upper lip;
    ·         50[10]-60% have a congenital heart disease (most commonly single atrium)[11].
    ·         The majority of survivors are of normal intelligence[12].
    Short-rib polydactyly syndromes:
    descriptive category for a group of lethal skeletal dysplasias characterized by a hypoplastic thorax, short ribs, short limbs, polydactyly and visceral abnormalities6,[13].
    Recently Ho et al. suggested that the Verma–Naumoff syndrome (type 3 short-rib polydactyly syndrome) and Jeune syndrome are variants of the same genetic disorder[14].
    Associated anomalies: Multiple organ anomalies are reported:
    Associated liver disease: hepatic ductal hypoplasia[15], biliary cirrhosis and extensive fibrosis[16],[17];
    ·         Pancreatic cysts[18] and pancreatic fibrosis10,12;
    ·         Hirschsprung disease[19];
    ·         Agenesis of the corpus callosum, Dandy-Walker malformation15 and ventriculomegaly10;
    ·         Situs inversus10,12;
    ·         Single umbilical artery, polyhydramnios10,18;
    ·         Renal glomerular sclerosis12;
    ·         Increased nuchal translucency[20];
    ·         Visual loss and night blindness[21] (retinal degeneration);
    ·         Mild mental retardation12,[22];
    ·         Hypoplastic hair and skin, oligodontia22;
    ·         Cleft lip and/or palate3,[23].
    Histopathology: Yang et al.[24] suggested 2 types of Jeune syndrome from clinicopathological examination:
    type 1: radiologically: irregular metaphyseal ends,
    histopathologically: irregular cartilage bone junction with patchy distribution of
    physeal zone of hypertrophy;
                type 2: radiologically: smooth metaphyseal ends,            histopathologically: diffusely retarded and disorganized physes with smooth             cartilage bone junctions.
    Prognosis: 70% have a fatal outcome in the neonatal period10,11. Lung hypoplasia due to a small thoracic cage, causes often a fatal respiratory failure12,[25]. However surgical thoracic expansion (with methyl-methacrylate prosthesis) has been used successfully in some patients[26],[27].
    Patients who survive respiratory failure may have an improvement in the relative growth of the thoracic cage and might have slight to moderate shortness of stature. In the other hand these survivors frequently may suffer from severe renal involvement, leading to renal insufficiency10,[28]. Amirou et al. reported a case of successful renal transplantation in a 10-year-old boy with Jeune syndrome28.
    Progressive hepatic dysfunction appears16 and may contribute to a poor long-term prognosis.
    Survival to the fourth decade has occurred12.
    Recurrence risk: autosomal recessive: 25%
    Management: Termination of pregnancy can be offered before viability. Postnatal confirmation of the diagnosis is important for genetic counseling and future pregnancies.
  • Genetic anomalies: Defect probably located on the short arm of chromosome 12.
    Differential diagnosis: Ellis van Crevelt syndrome (Short arm of chromosome 4) that presents mainly with cardiac anomalies instead of renal anomalies.
    Prognosis: In spite of the dreadful name not all newborn are asphyxiated, and with corrective surgery of the chest some patient have had a fairly normal outcome
    Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation the pregnancy is opted for. Confirmation of diagnosis after birth is important for genetic counseling.
  • Definition: Anomaly due to defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase with 3 subtypes. A lethal type 1 with prenatal manifestations of short demineralized long bones, craniosynostosis and neonatal hypercalcemia; a type 2with rickets-like skeletal changes, fractures and premature loss of teeth; and a type 3 with only metabolic anomalies detected on biochemical screening.
    Synonyms: Phosphoethanolaminuria.
    Incidence: Rare.
    Etiology: Autosomal recessive. Carriers can be recognized by their low levels of serum alkaline phosphatase[1] and urinary phosphoethanolamine
    Recurrence risk: 25%.
    Diagnosis: The diagnosis should be suspected in fetus with micromelia, and demineralization of the bones. Spurs have been diagnosed postnatally that might be typical. These occur along the midshaft of long bones and at the knees and elbows[2],[3],[4].
    Pathogenesis: Anomaly of tissue-nonspecific alkaline phosphatase (TNSALP) gene.
    Genetic anomaly: The type 1 and type 2 are different disorders. There are numerous variant tissue-nonspecific alkaline phosphatase genes[5].
    Associated anomalies: See definition.
    Differential diagnosis: Hypophosphatasia is probably indistinguishable on ultrasound criteria only from Osteogenesis imperfecta Type II and Achondrogenesis type IA.
    Prognosis: Lethal for the Type 1.
    Management: In suspected fetus (25% recurrence risk) termination of the pregnancy can be offered.
  • Background: First described in 1914 [1] . It is a rare congenital syndrome caused by a peroxisomal dysfunction1, [2] , [3] . It is one of the four syndromes of the  “peroxisome biogenesis disorders” resulting from anomalous enzymatic function of the metabolism of the fatty acids3 .

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    Articles » Skeletal » Campomelic dysplasia
    2000-07-24-01 Campomelic dysplasia © Silva www.thefetus.net/
    Campomelic dysplasia
    Updated 2006-01-18 by Juliana Leite, MD
    Original text 2000-07-24 Philippe Jeanty, MD, PhD & Sandra R Silva, MD
    Definition: Campomelic dysplasia is a congenital disorder characterized by development of abnormal curvature of the long bones, particularly from lower extremities, such as femur and tibiae[1]. Some authors have classified the disease into two varieties: “long limbed” and “short limbed,” depending on the type of limbs involved in the pathological process[2].
    Synonyms: Camptomelic dysplasia, campomelic syndrome, campomelic dwarfism, congenital bowing of the limbs[3].
    Prevalence: The disorder affects 0.02:10,000 live births[4]. Sex reversal occurs in some genotypic males with lack the H-Y antigen. Phenotypic sex ratio is approximately M1:F2.3, karyotypic sex ratio is approximately M2:F13.
    Etiology: The transmission of campomelic dysplasia is still discussed. Autosomal recessive inheritance is thought to be the most common pattern, although it may happens also due to sporadic autosomal dominant mutation[5].
    Recurrence risk: Depends on the etiology. If transmitted by autosomal recessive pattern it has a 25% recurrence risk. When transmitted by autosomal dominant pattern, it has 50% recurrence risk, but in fact most are new mutations.
    Diagnosis: The most characteristic sign of campomelic dysplasia is the marked anterior bowing of the long bones, particularly of femur (figs. 1-2) and tibia. Severe angulation may mimic fractures. Other sonographic features that are commonly present include, growth restriction, bell-shaped narrow chest, eleven pair of ribs, hypoplasia of the mid-thoracic vertebral bodies, fibula, and scapula, scoliosis, shortness of the limbs, talipes equinovarus, tracheobronchomalacia, flat and small face, high forehead with prominent occiput, low nasal bridge, micrognathia, cleft of the soft palate, hypertelorism, low-set and malformed ears, hydrocephalus, and ambiguous genitalia[6].  
    Figure 1: Bowing of the ulna. Note the gentle curve that sometimes differentiate these from the more acute angles of the osteogenesis imperfecta fetuses.
    Figure 2: Bowing of the femur.
    Genetic anomaly: A mutation in SOX9, a sex-determining region of Y (SRY)[7] related gene, located at 17q24 seems to be associated with the occurrence of both campomelic dysplasia and sex reversal[8].
    Pathogenesis: Although many theories have been proposed to explain the development of the anomalies present in this syndrome, (in particular the bowing of the bones), the precise mechanism is not known.  Some of the theories are:
    1)       mechanical stress due to faulty fetal position within the uterus[9].
    2)        primary muscle imbalance and shortening, particularly of the calf muscles causing secondary bending of the tibia[10].
    3)        intrauterine fracture with subsequent healing[11].
    4)        abnormal vascular and cellular elements of perichondrium[12].
    5)        developmental disturbance in the cartilagineous phase of bone formation[13].
    Associated anomalies: Polyhydramnios, and anomalies from the central nervous, cardiac, and renal systems have been described prenataly6. After birth, hearing loss may occur.
    Differential diagnosis: Osteogenesis imperfecta type I and II, hypophosphatasia, unclassifiable varieties of congenital bowing of the long bones[14], thanatophoric dysplasia, mesomelic dysplasia (Reinhart variety)[15], Roberts syndrome and diastrophic dysplasia5.   
    Prognosis: Almost all result in neonatal or infant death, due to respiratory complications. Some survivors,  including a boy alive at 17 years, have been reported[16].
    Management: Before viability, the option of pregnancy termination should be offered. After viability, standard obstetrical management is not altered, and respiratory function in the newborn must be supported.
  • Chest & spine
    .V hypoplastic scapulae (92%)
    .V narrow bell-shaped chest
    .V hypoplastic vertebral bodies +non mineralized pedicles
    (especially lower cervical spine)
    @ Pelvis
    .V vertically narrowed iliac bones
    .V vertical inclination of ischii
    .V wide symphysis
    .V narrow iliac bones with small wings
    .V shallow acetabulum
    @ Extremities (lower extremity more severely affected)
    .V dislocation of hips + knees
    .V anterior bowing(= campto) of long bones: marked in
    tibia+ moderate in femur
    .V hypoplastic fibula
    .V small secondary ossification center of knee
    .V small primary ossification center of talus
    .V clubfoot
  • ×