The Diagnosis of a Skeletal Dysplasia.
A skeletal dysplasia is usually suspected when the antenatal ultrasound shows disproportionately short limbs compared with the size of the head and body.
There are over 350 different types of skeletal dysplasias3,
and there are other conditions such as aneuploidies that can mimic these diseases. Investigation of a suspected skeletal dysplasia should begin with a detailed ultrasound scan,
including measurements of all the long bones,
the head,
chest and abdomen,
as well as detailed imaging of the spine and organs for any associated abnormalities. It is very difficult to correctly diagnose a specific skeletal dysplasia on the basis of ultrasound alone. It has been shown that ultrasound can predict with high accuracy the lethality of a skeletal dysplasia1,
4,
5. The ability to counsel on the basis of whether the unborn child will survive or not is very useful to the parents. A definite diagnosis is obtained in only 70 - 80% of cases,
even after clinical,
radiological,
pathological,
biochemical and genetic investigations1,
4. In our experience,
the parental relationship has been consanguineous in a number of cases.
There are several indicators of a poor prognosis in skeletal dysplasias1,
2,
6. These are listed below.
1. Small Chest Size.
Death as a result of a skeletal dysplasia is usually due to a small chest and associated pulmonary hypoplasia. A chest circumference < 5th percentile for gestational age is an indicator of pulmonary hypoplasia2. A chest-to-abdominal circumference ratio of < 0.6 is strongly suggestive of a lethal disorder3.
2. Severely Shortened Long Bones.
The shorter the fetal long bones,
the higher the likelihood of a lethal disorder. A femur length that is less than 2 standard deviations below the mean for gestational age should provoke measurements of all the long bones to investigate a potential skeletal dysplasia.
3. Abnormally Bent or Curved Bones.
Bending is a feature of many lethal skeletal dysplasias including thanatophoric dysplasia,
or can be the result of fractures in conditions such as osteogenesis imperfecta or hypophosphatasia. Very few non-lethal dysplasias show bent or curved bones antenatally.
4. Evident at an Early Age.
The most severe dysplasias such as achondrogenesis are evident in the first trimester,
whereas the less-severe,
non-lethal conditions such as achondroplasia may not become obvious until the 3rd trimester. Hence,
the earlier a condition can be detected antenatally,
the poorer the long term prognosis.
5. Low Femur Length-to-Abdominal Circumference Ratio.
This ratio was introduced into the literature in 19976,
7. It has been shown that a femur length-to-abdominal circumference ratio of < 0.16 results in a lethal outcome in almost all cases,
whereas a ratio of > 0.16 resulted in survival6,
7.
6. Fetal Hydrops.
Hydrops occurs in the most severe of the skeletal dysplasias,
as well as aneuploidies which can mimic a skeletal disorder.
The Most Common Skeletal Dysplasias.
Thanatophoric Dysplasia.
There are 2 subtypes thanatophoric dysplasia (TD),
the most common of the lethal skeletal dysplasias. Both result from a new autosomal dominant mutation on chromosome 48. Almost all affected neonates die within days of birth due to respiratory insufficiency. The ultrasound features are (Fig. 1, Fig. 2):
- severe micromelic limb shortening
- pronounced curvature of the limb bones
- relatively large head
- small thoracic cage
- polyhydramnios
The radiological manifestations include (Fig. 3):
- macrocephaly with small face,
“clover-leaf” skull in some
- long narrow thoracic cage with short ribs
- severe platyspondyly,
“U” or “H” shape vertebra on AP projection
- short,
bowed long bones,
“French telephone receiver” femurs (TD I),
straight femurs (TD II)
- short,
small iliac bones with horizontal acetabular roofs
- increased subcutaneous tissues
Achondroplasia.
Achondroplasia is the most common non-lethal skeletal dysplasia with an incidence of about 1 in 25 000 births8. It has an autosomal dominant inheritance on chromosome 4,
with 80% of cases due to new mutations8. It is usually diagnosed postnatally,
or antenatally in the third trimester,
when polyhydramnios causes the pregnancy to seem large for dates. Homozygous achondroplasia can be diagnosed much earlier in the pregnancy,
and is usually hereditary. The ultrasound features are (Fig. 4,
Fig. 5,
Fig. 6):
- normal 19 week morphology scan
- drop off in growth of the long bones in the 3rd trimester
- relative macrocephaly
- frontal bossing
- saddle nose
- polyhydramnios
The radiological manifestations include (Fig. 7):
- large cranium with a narrow foramen magnum and J-shaped sella
- short,
flat vertebral bodies with short pedicles and narrow vertebral canal
- pronounced lumbar lordosis
- “champagne glass” pelvis with narrow sciatic notches
- micromelic shortening of the long bones with flared metaphyses
- mildly shortened ribs
Osteogenesis Imperfecta.
There are 4 main subtypes of osteogenesis imperfect (OI) which range from the clinically mild types I and IV which are usually diagnosed in childhood,
to the lethal type II. Only the severe types are diagnosable on imaging antenatally. As a group,
they are one of the most common of all skeletal dysplasias,
most resulting from a gene defect on chromosome 17. The incidence is about 1 in 25 000 births8,
although this may be higher as around 10% are subclinical. The frequency and inheritance are summarised in Table 18.
Type |
Frequency |
Inheritance |
Clinical Severity |
I |
~50% |
autosomal dominant |
mild to moderate |
II |
~25% |
usually autosomal recessive |
perinatal lethal |
III |
~21% |
autosomal,
75% dominant,
25% recessive |
progressive deforming |
IV |
rare |
autosomal dominant |
mild to moderate |
Table 1.
Subtypes of Osteogenesis Imperfecta.
The ultrasound features are (Fig. 8,
Fig. 9, Fig. 10):
- “too-well seen” anatomy – the poor mineralization allows sounds waves to pass through the bones easily
- short,
bent or crooked bones,
as a result of multiple fractures
- compressible skull
The radiological manifestations include (Fig. 11):
- very poorly ossified bones,
especially the skull
- wormian bones
- crumpled long bones
- short,
beaded ribs
- flattened acetabulae and iliac wings
Achondrogenesis.
Achondrogenesis is one of the most severe skeletal dysplasia and can be diagnosed as early as the late first trimester. There are several subtypes although the radiological features are similar. The incidence is around 1 in 50 000 live births8,
although most fetuses are stillborn. The ultrasound features are (Fig. 12):
- severe micromelia
- fetal hydrops
- very short beaded ribs
- deficient or absent vertebral ossification
- barrel-shaped chest and distended abdomen
- polyhydramnios
The radiological manifestations include (Fig. 13):
- poorly mineralized skull
- short,
splayed ribs
- short,
broad,
bowed tubular bones
- minimal vertebral body ossification
- short,
deformed iliac wings
- increased soft tissues (hydrops)
Other Interesting Skeletal Dysplasias.
Hypophosphatasia.
This lethal skeletal dysplasia can be overlooked antenatally due to subtle ultrasound findings. The disease is uncommon,
with an incidence of 1 in 100 000 live births8,
and results from a defect on chromosome 1 that is inherited in an autosomal recessive fashion. The ultrasound features are (Fig. 14):
- “too-well-seen” anatomy – due to lack of bone mineralization
- shortened,
deformed limbs
- polyhydramnios
The radiological manifestations include (Fig. 15):
- very poor mineralization of bones – “jelly-baby”
- almost no calvarial ossification (cranium membranosum)
- marked retardation of skeletal ossification
- very small chest,
with small ribs
- abnormally shaped vertebral bodies – clefting,
platyspondyly
Atelosteogenesis.
Most subtypes of this severe skeletal dysplasia are neonatally lethal. Cases have been reported of both dominant and recessive types,
with defects on chromosomes 3,
4 and 59. All types shows severe rhizomelic limb shortening and facial abnormalities. The ultrasound features are (Fig. 16):
- very short tubular bones,
including hypoplastic femurs and,
sometimes,
absent humeri
- boomerang-shaped tibia
- clefted vertebrae
- cleft lip and palate
- micrognathia
- omphalocoele
The radiological features include (Fig. 17):
- absent,
short or clubbed humeri
- short,
flared femurs
- short,
bowed radius,
ulna and tibia,
hypoplastic fibula
- hypoplastic vertebra,
vertebral clefting,
platyspondyly
- 11 – 12 short ribs
- hypoplastic maxilla and mandible
- “hitch-hiker thumb” – characteristic feature of Type II8,9
Short-Rib Polydactyly Syndrome.
This is an autosomal recessive disorder with several subtypes8. Despite the name,
polydactyly is not always present,
especially in subtypes III and IV. The condition is almost universally lethal in the neonatal period. The ultrasound features are (Fig. 18,
Fig. 19):
- short ribs and long bones
- polydactyly
- narrow chest
- cystic hygroma
- choroid plexus cysts
- brain and renal abnormalities in type II and IV (vermian hypoplasia,
arhinencephaly,
cystic kidneys)
- hydrops
The radiological features include (Fig. 20):
- very short,
horizontal ribs
- micromelia,
hypoplastic tubular bones with ragged ends,
pointed femoral ends
- polydactyly
- dolichocephaly with poorly mineralized frontal bones
- micrognathia
- misshapen vertebral bodies with coronal clefting
Arthrogryposis.
Arthogryposis refers to a heterogeneous group of disorders characterised primarily by joint contractures. The clinical features are very varied depending on the underlying cause,
but the antenatal ultrasound features are similar in all these disorders. Final diagnosis is obtained via muscle biopsy and genetic investigations. The ultrasound features are (Fig. 21,
Fig. 22):
- absent or severely reduced fetal movements during scanning
- failure of fetus to change position during scanning
- fixed flexion/extension of limbs
- clasped thumbs
- cystic hygroma
The radiological features include (Fig. 23):
- slender,
osteoporotic bones
- fixed flexion deformities,
joint dislocations
- vertical talus with rocker-bottom feet
- brachycephaly
Important Mimics of Skeletal Dysplasias.
Severe Intrauterine Growth Restriction (IUGR).
In cases of severe IUGR,
the fetal long bones may be quite short,
mimicking a skeletal dysplasia10. As such,
we recommend that an examination of fetal well-being including Doppler ultrasound be performed as well as a detailed examination of the placenta. IUGR is defined as being present if the fetal weight is below the 10th percentile for gestational age. The prevalence of IUGR is 3 – 5%,
and is higher in women with hypertension or IUGR in a previous pregnancy11. The ultrasound features are (Fig. 24,
Fig. 25,
Fig. 26):
- abnormal fetal biometry – small abdomen with poor growth,
shortened long bones,
head measurement may be normal or small
- oligohydramnios
- abnormal umbilical artery dopplers – elevated SD ratios,
absent or reversed end diastolic flow
- abnormal middle cerebral artery dopplers – increased diastolic flow and abnormal resistive indices
- abnormal placenta in many cases – small or calcified placenta,
marginal or velomentous cord insertion
- echogenic bowel in up to 20%
Chronic Intervillous Histiocytosis.
Chronic intervillous histiocytosis (CIH) or chronic intervillositis is a rare inflammatory disorder of the placenta resulting in extreme IUGR and recurrent pregnancy losses12. The skeletal findings can be striking,
mimicking a severe skeletal dysplasia (Fig. 27,
Fig. 28, Fig. 29) .