role of medical imaging in achondroplasia dr. muhammad bin zulfiqar

ROLE OF SONOGRAPHIC IMAGING IN ACHONDROPLASIADr. Muhammad Bin ZulfiqarPGR IV FCPS Services Institute of Medical Sciences / [email protected]

AIMS• To look for Antenatal US imaging in Achondroplasia.

• To differentiate between homozygous / heterozygous achondroplasia

• Role of plain radiography , CT and MRI

ACHONDROPLASIA• Rhizomelic micromelia associated with frontal bossing and low nasal bridge.

• Types:• Heterozygous—Compatible with life• Homozygous—Incompatible with life

HETEROZYGOUS ACHONDROPLASIA

• Prototype of rhizomelic dwarfism

• Autosomal dominant I sporadic (80%) disease with quantitatively defective endochondral bone formation

• Related to advanced paternal age

• Epiphyseal maturation +ossification unaffected

OB-US (DIAGNOSABLE >21-27TH WEEK GA):

• Shortening of proximal long bones: femur length <99th percentile between 21 and 27 weeks MA

• Increased BPD, HC, HC AC ratio• Decreased FL BPD ratio• Normal mineralization, no fractures• Normal thorax + normal cardiothoracic ratio• Three-pronged(= trident) hand= 2nd+ 3rd +4th finger of similarly short length without completely approximating each other(= PATHOGNOMONIC)

CASE—1HETEROZYGOUS ACHONDROPLASIA

Mrs. M., 34 years old, housewife, G7P5, with no consanguinity, was admitted at 33 weeks of gestation to antenatal ward for evaluation of fetus in view of tense polyhydramnios.

Yuliya Burmagina, MD; Ekaterina Kaloyanova, MD. 20087-06-16-21 Achondroplasia © Burmagina www.thefetus.net/

• Frontal Bossing• Flattened Nasal Bridge

• Abnormal head shape: brachycephaly with starting craniosynostosis.

• Characteristic profile and head shape (prefrontal edema, frontal bossing, typical appearance of nasal bridge (midface hypoplasia) and short cranial base).

• “Bell-shaped" trunk (narrow thorax and distended abdomen), frontal bossing. Note the polyhydramnios.

• Note the significant difference in circumferences of abdomen and thorax (along with relative cardiomegaly)

• Normal kidney size and sonographic pattern (enabling better differential diagnosis).

• Absence of polydactyly (helping to differentiate the condition).

• Short femur length=58 mm, <5centile, fibula & tibia. Humerus (=52 mm, < 2centile).

• Note shortened arm (ulna=51 mm, <5 centile).

• X-ray study few days after birth: Narrow chest, shortened long bones (no evidence of platyspondyly).

CASE—2HETEROZYGOUS ACHONDROPLASIA

A 21-year-old G2P1 at 36 weeks of pregnancy of gestation. Her husband has some family history of achondroplasia.

• 36 weeks of pregnancy; the image 1 shows a normal head circumference corresponding to 36+3 weeks of pregnancy. The image 2 shows a short fetal femur corresponding only to 26+3 weeks of pregnancy.

• 36 weeks of pregnancy; the images show short long bones of the fetus corresponding to 27 weeks (humerus; image 3) and 30 weeks of pregnancy (tibia; image 4).

• 3D image of the fetal face with the low nasal bridge and midface hypoplasia.

• The images compare the prenatal 3D image and postnatal appearance of the baby.

•Radiography•CT Scan•MRI

HETEROZYGOUS ACHONDROPLASIASKULL

• Large calvarium with frontal bossing• Depression of nasion• Broad mandible• Constricted basicranium + small foramen magnum:• Communicating hydrocephalus caused by obstruction of basal cisterns + aqueduct

• Image shows an enlarged calvaria with a shortened skull base and frontal bossing. Note the midface hypoplasia.

• Enlarged calvaria. Note the enlarged mandible.

• Typical findings of skull base achondroplasia; Large skull vault with small skull base, narrow foramen magnum, prominent forehead, depressed nasal bridge, dilated suprasellar cistern, vertical straight sinus and dilated supratentorial ventricular system with normal 4th ventricle.

• There is evidence of stenosis of the foramen magnum.

• Achondroplasia. Sagittal section of the cervical spine on a T2-weighted magnetic resonance image in a 6-year-old patient who presented with a neurologic deficit. This image shows narrowing of the foramen magnum at the C1 canal, effacement of the subarachnoid spaces at the cervicomedullary junction, and abnormal intrinsic cord signal intensity.


CHEST• Anteroposterior narrowing of chest

• Short anteriorly flared concave ribs

• Squaring of inferior scapular margin

• Shortened ribs.

HETEROZYGOUS ACHONDROPLASIASPINE

• .Hypoplastic bullet / wedge-shaped vertebra:• Rounded anterior beaking of vertebra in upper lumbar spine (DDx: Hurler disease)

• Decreased vertebral height• Scalloped posteriorly concave vertebral margin• Scoliosis:

• Thoracolumbar angular kyphosis (gibbus)• Exaggerated sacral lordosis

HETEROZYGOUS ACHONDROPLASIASPINE

• Stenosis of lumbar spine:• Narrowing of interpedicular space due to laminar thickening

• Ventrodorsal narrowing of spine due to short pedicles• Bulging / herniation of intervertebral disks

• Wide intervertebral foramina

• Image shows progressive narrowing of the lumbar spinal canal, bullet-nose vertebrae, Note the shortened ribs

• Image shows progressive reduction in vertebral interpediculate distance in the caudal direction.

• The spine is often affected in achondroplasia. Features include interpediculate narrowing and thickened pedicles.

• Disk herniation is common. Changes in the spine can result in stenosis of the spinal canal, particularly in the lumbar region.

• Image shows a decreased lumbar interpedicular distance. Note the scoliosis.

• short pedicles• posterior vertebral scalloping

• thoracolumbar kyphosis• tombstone iliac wings

HETEROZYGOUS ACHONDROPLASIAPELVIS

• Square flattened iliac bones = Tombstone configuration

• Champagne glass"-shaped pelvic inlet• Lack of flaring of iliac wings• Horizontal acetabula(= flat acetabular angle)• Small sacrosciatic notch

• Champagne-glass pelvis with squared iliac wings, a narrow sacroiliac notch, and a reduced acetabular angle.

• Image shows progressive narrowing of the interpediculate distance with a champagne-glass pelvis. Note that the legs are straight in infancy.

HETEROZYGOUS ACHONDROPLASIAEXTREMITIES

• Predominantly rhizomelic micromelia of long bones (femur, humerus):

• “Trumpet" appearance of long bones = shortening with disproportionate metaphyseal flaring (actually normal width of metaphysis)

• Short femoral necks• Limb bowing


EXTREMITIES• Ball-in-socket" epiphysis = broad V-shaped distal femoral metaphysis in which epiphysis is incorporated

• High position of fibular head(= disproportionately long fibula)

• Short ulna with thick proximal + slender distal end• Brachydactyly (short tubular bones of hand+ feet), especially short proximal + middle phalanges

• Image shows inverted femoral physis (inverted V configuration), which contributes to a waddling gait.

• Genu varum. Image shows rhizomelic shortening of the bilateral femurs with metaphyseal flaring. The bones are wide because of unaffected appositional growth.

• Image shows rhizomelic shortening of the humerus with posterior bowing and an incomplete glenoid fossa.

• Image shows posterior bowing of the humerus, the principal cause of the loss of elbow extension. Posterior dislocation of the radial head may also contribute.

• Trident hands. Image shows widely opposed fingers of equal length.

• Trident hands.

COMPLICATIONS OF ACHONDROPLASIA

(1) Hydrocephalus + syringomyelia (small foramen magnum)(2) Recurrent ear infection (poorly developed facial bones)(3) Neurologic complications (compression of spinal cord, lower brainstem, cauda equina, nerve roots): apnea and sudden death(4) Crowded dentition+ malocclusion

HOMOZYGOUS ACHONDROPLASIA

• Hereditary autosomal dominant disease with severe features of achondroplasia (disproportionate limb shortening, more marked proximally than distally)

• Risk: marriage of two achondroplasts to each other


• Skull:• Large cranium with short base + small face• Flattened nose bridge

• Short ribs with flared ends• Vertebra:

• Hypoplastic vertebral bodies• Decreased interpedicular distance


• Pelvis:• Short squared innominate bones• Flattened acetabular roof• Small sciatic notch

• Limb Bones:• Short limb bones with flared metaphyses• Short, broad, widely spaced tubular bones of hand

INDICES DEPICTING FATAL OUTCOME

• FL / AC ratio <0.16---Lethal outcome• FL / AC ratio >0.16---Non lethal outcome• Normal thoracic / abdominal circumference ratio is 0.89-1.0• TC /AC ratio of < 0.8 is associated with Pulmonary hypoplasia

and lethality.

Antenatal Detection of Skeletal Dysplasias Barbara V. Parilla, MD, Elizabeth A. Leeth, MS, Michelle P. Kambich, MS, Patricia Chilis, RDMS and Scott N. MacGregor, DO . Division of Maternal-Fetal Medicine, , Northwestern University Medical School, Evanston, Illinois USA. J Ultrasound Med 22:255-258 • 0278-4297.Johnson A, Callan NA, Bhutani VK, Colmorgen GH, Weiner S, Bolognese RJ. Ultrasonic ratio of fetal thoracic to abdominal circumference: an association with fetal pulmonary hypoplasia. Am J Obstet Gynecol 1987; 157:764–769.

THORACIC CIRCUMFERENCE• Preparation: Full bladder for TA imaging in first and

second trimester• Method: excluding the skin and subcutaneous tissues at

the level of four chamber view of the heart.• Normal thoracic / abdominal circumference ratio is •0.89-1.0• TC /AC ratio of < 0.8 is associated with Pulmonary

hypoplasia and lethality.Johnson A, Callan NA, Bhutani VK, Colmorgen GH, Weiner S, Bolognese RJ. Ultrasonic ratio of fetal thoracic to abdominal circumference: an association with fetal pulmonary hypoplasia. Am J Obstet Gynecol 1987; 157:764–769.

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.

• 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).

• Short ribs with flared ends, hypoplastic vertebral bodies (platyspondyly), flat acetabular roof and small sciatic notches favor Homozygous Achondroplasia

CASEACHONDROPLASIA19 years male

CASEACHONDROPLASIAThree month old child

•Foramen magnum stenosis with significant compression of the cervico-medullary junction.

CASEACHONDROPLASIATwo Years Female Child

CASEACHONDROPLASIAThree month old child

CASEACHONDROPLASIA50 years female

• Bilateral knee x-rays show metaphyseal flaring typical of achondroplasia.

CASEACHONDROPLASIA 14 Years Male

• Rhizomelic dwarfism, with relatively short femora

• Bilateral genu vara.• Metaphyseal flaring, most evident at the lower femora, giving trumpet bone type appearance

• Relatively long fibulae.• V shaped growth plates, most evident at the upper tibiae

• Shortened long bones of the upper and lower limbs with metaphyseal flaring.

• Anterior Flaring of the ribs.

• Small pelvis (trident pelvis).

• Shortened long bones of the upper and lower limbs with metaphyseal flaring.

• Anterior Flaring of the ribs. • Small pelvis (trident pelvis).

• Typical findings of skull base achondroplasia; Large skull vault with small skull base, narrow foramen magnum, prominent forehead, depressed nasal bridge, dilated suprasellar cistern, vertical straight sinus and dilated supratentorial ventricular system with normal 4th ventricle.

• stenosis of the foramen magnum with a large skull

• trident hands

• metaphyseal flaring giving a trumpet bone type appearance

• the femora and humeri are particularly shortened (rhizomelic shortening)

• the acetabular roof is horizontal, the iliac wings have a tombstone appearance

• horizontal sacrum

• progressive decrease in interpedicular distance in lumbar spine

Role of CT

• CI axial section images of the foramen magnum of four patients with achondropbasia. (a) Four-month-old patient; (b) 8-monthold

• patient; (c) il-month-old patient; (d) 2-year-old patient. The contour of the posterior two-thirds of the foramen magnum varies, whereas

• the anterior third maintains a constant and symmetric shape.

• The posterior margin of the foramen magnum extends anteriorly (arrow) beyond the posterior arch of C1 and impinges on the posterior surface of the bower medulla oblongata and the upper cervical cord.

• The posterior margin of the foramen magnum protrudes inferiorly (arrow) and extends ventral to the posterior arch of C-1, further decreasing the AP diameter of the spinal canal.

• Coronal reformatted CT image shows the thickened, deformed left lateral margin of the foramen magnum (arrow) compressing the neural tissue. The subarachnoid space was opacified with intrathecal metrizamide (arrowhead) (metrizamide was black on the negative image display).

• The mid-sagittal view shows kinking and narrowing of an “hourglass deformity” of the cord at the cervicomedullary junction (arrow) with a thin layer of CSF interposed between the cervical cord and the posterior margin of the foramen magnum.

• MR sagittal image (0.5 1) of the craniocervical junction with SE 538/38 (repetition time m sec/echo time m sec): the margin of the foramen magnum is not clearly defined.

• However, the brain stem cord outline is well delineated; note the abnormal focal cord narrowing from C-i to C-2 bevel

CARDIAOTHORACIC AND HC / AC RATIO

• HC / AC 1.207 at 14 week's but decreased slowly until 30 week's when the ratio was 1.110 thereafter there was a rather sharp fall in the mean ratio 1.010 at 36 weeks and 0.967 at 40 weeks and then the variability decreases.

DD ELLIS VAN CREVALD SYNDROME

• Ellis-van Creveld (EVC) syndrome is a differential diagnosis of short-limb dwarfisms. It is also known as chondroectodermal dysplasia. This autosomal recessive disease involves chromosome 4p16. The hands demonstrate polydactyly in almost all patients, whereas the feet demonstrate polydactyly in only 10%. Note the broad hands with short middle phalanges and hypoplastic distal phalanges. The carpal bones are malformed, with fusion of the capitate and hamate. Extracarpal bones might also be present. The ends of the ulna and radius are enlarged.

• Ellis-van Crevald (EVC) syndrome. (See the previous image.)

• The knees of patients with Ellis-van Creveld (EVC) syndrome develop a genu valgus deformity, and the long bones are short. Hypoplasia of the proximal tibia is also present. (See the previous 2 images.)

• The knees of patients with Ellis-van Creveld (EVC) syndrome develop a genu valgus deformity, and the long bones are short. Hypoplasia of the proximal tibia is also present. (See the previous 3 images.)

• The thoracic cavity of this patient with Ellis-van Creveld (EVC) syndrome is small and narrow, with short ribs. About 60% of patients have cardiac anomalies, and most patients ultimately die from respiratory illness.

• In Ellis-van Creveld (EVC) syndrome, the teeth are hypoplastic, as are the nails. The teeth are small and cone shaped, with irregular spacing. Other facial anomalies include a partial harelip.

• Metaphyseal chondroplasia (Schmid type) is a differential diagnosis of achondroplasia, with metaphyseal flaring of the ulna and radius as well as bowing of the shaft. Note no hand involvement with metaphyseal chondroplasia, unlike achondroplasia.

• Metatrophic dwarfism II, or Kniest syndrome, is a differential diagnosis. Skeletal dysplasia results in short limbs and a proportionally long trunk; however, the head and face appear normal. With time, severe kyphoscoliosis produces marked shortening of the trunk, which can make body proportions deceiving.

CASEACHONDROPLASIATWO YEARS MALE

• The skull vault is enlarged, with small skull base.

• There is exacerbation of the lumbar-sacral angle and the interpedicular distance gradually diminishes in the lumbar spine. The iliac wings are vertical.

• The limbs demonstrate normal density with marked shortening of the long bones.

• The skull vault is enlarged, with small skull base.• There is exacerbation of the lumbar-sacral angle and the

interpedicular distance gradually diminishes in the lumbar spine. The iliac wings are vertical.

• The limbs demonstrate normal density with marked shortening of the long bones.

• There is evidence of stenosis of the foramen magnum.

CASEACHONDROPLASIA

• There is a relatively large cranial vault with small skull base. There is a prominent forehead with depressed nasal bridge. The foramen magnum is narrowed, and there is a cervicomedullary kink. Relative elevation of the brainstem gives rise to a large suprasellar cistern and a vertically-oriented straight sinus.

TAKE HOME MESSAGE• Antenatal Diagnosis is possible with confident.

• Antenatal Differentiation between lethal and non lethal dysplasia is possible.

• Radiography, CT and MRI are helpful in • Postnatal workup• to look for complications.

THANK YOU

role of medical imaging in achondroplasia dr. muhammad bin zulfiqar

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