Skeleton Flashcards
What abnormalities are associated with the Skeleton in pregnancies?
14 Skeletal Dysplasia Achondrogenesis Achondroplasia Asphyxiating Thoracic Dystrophy Atelosteogenesis Campomelic Dysplasia Craniosynostosis Diastrophic Dysplasia Ellis-Van Creveld Syndrome Hypophosphatasia Jarcho-Levin Syndrome Osteogenesis Imperfecta Short Rib Polydactyly Syndrome Thanatophoric Dysplasia
Skeletal Dysplasia
Prevalence: 1 in 4,000 births.
25% are stillborn and 30% die in the neonatal period.
Approach to prenatal diagnosis: There is a wide range of rare skeletal dyplasias, each with a specific recurrence risk, dysmorphic expression, and implications for neonatal survival and quality of life.
The incidental discovery of a skeletal dysplasia on routine ultrasound screening, in a pregnancy not known to be at risk of a specific syndrome, necessitates a systematic examination of the limbs, head, thorax and spine to arrive at the correct diagnosis.
Assessment of long bones:
Shortening of the extremities can involve the entire limb (micromelia), the humerus or femur (rhizomelia), the radius, ulna, tibia or fibula (mesomelia) or the hands and feet (acromelia). The femur is abnormally short even in mesomelic dwarfism and, therefore, in routine fetal abnormality screening the femur is measured and compared subjectively to all long bones. Severe limb reductions, as in thanatophoric dwarfism and achondrogenesis can be detected from 16 weeks’ gestation, whereas in achondroplasia limb shortening becomes obvious >22 weeks.
Abnormal shape. In some conditions there is pronounced bowing (e.g. campomelic dysplasia, thanatophoric dwarfism), and in others fractures and callus formation may also be detected (e.g. osteogenesis imperfecta, achondrogenesis and hypophosphatasia).
Reduced echogenicity of bones due to hypomineralization is seen in some disorders (e.g. hypophosphatasia, osteogenesis imperfecta and achondrogenesis). Virtual absence of ossification of the spine in achondrogenesis, may lead to the erroneous diagnosis of complete spinal agenesis. Poor mineralization of the skull in hypophosphatasia, may result in the misdiagnosis of hydrocephalus.
Absence of extremities, such as amelia (complete absence of extremities), acheiria (absence of the hand), phocomelia (seal limb) or aplasia–hypoplasia of the radius or ulna, are often inherited as part of a genetic syndrome (Holt–Oram syndrome, thrombocytopenia with absent radii syndrome). Another cause of focal limb loss is the amniotic band syndrome.
Evaluation of hands and feet: Several skeletal dysplasias are associated with alterations of the hands and feet.
Polydactyly: presence of more than five digits. It is classified as postaxial if the extra digits are on the ulnar or fibular side and preaxial if they are located on the radial or tibial side.
Syndactyly: soft tissue or bony fusion of adjacent digits.
Clinodactyly: deviation of a finger(s).
Disproportion between hands and feet and the other parts of the extremity may also be a sign of a skeletal dysplasia.
Examination of fetal movements: Arthrogryposis and multiple pterygium syndrome are characterized by limitation of flexion or extension of the limbs.
Evaluation of the fetal thorax: Several skeletal dysplasias are associated with a small thorax, which leads to pulmonary hypoplasia and neonatal death. The diagnosis of a small thorax can be made by examining the thoracic-to-abdominal circumference ratio or the thoracic-to-head circumference ratio. The thoracic circumference is measured at the level of the four-chamber view of the heart.
Evaluation of the fetal head: Several skeletal dysplasias are associated with reduced ossification of the skull bones. The face should also be examined for the diagnosis of hypertelorism, micrognathia, short upper lip, and abnormalities of the ears.
Diagnostic tests complementary to sonography: Prenatal or postnatal evaluation includes DNA analysis for an increasing number of skeletal dysplasia. Some can now be diagnosed by cfDNA testing of maternal blood. Postnatally, examination of skeletal radiographs is of particular importance, since the classification of skeletal dysplasias is largely based on radiographic findings.
Achondrogenesis
Prevalence: 1 in 40,000 births.
Second most common lethal skeletal dysplasia, after thanatophoric dysplasia.
Ultrasound: Severe shortening of the limbs, narrow thorax, short trunk length and large head. Associated with micrognathia, nuchal edema and polyhydramnios. There are 2 types of achondrogenesis: Type I (20%): autosomal recessive; there is poor mineralization of the skull and vertebral bodies, as well as rib fractures. Type II (80%): sporadic; there is poor mineralization of the vertebral bodies but not the skull and there are no rib fractures.
Assoc abnorm: -
Follow up: If pregnancy continues, follow-up should be standard.
Prognosis: The condition is lethal due to severe pulmonary hypoplasia.
Recurrence: Type I: 25%
Type II: no increased risk.
Achondroplasia
Prevalence: 1 in 25,000 births.
Ultrasound: Short limbs, short hands and fingers, large head with frontal bossing and depressed nasal bridge, and lumbar scoliosis.
Limb shortening and typical facial features become apparent >22 weeks’ gestation.
Assoc abnorm: -
Follow up: Follow-up scans every 4 weeks to monitor growth of the fetal head.
Prognosis: Homozygotic type: lethal due to severe pulmonary hypoplasia.
Heterozygotic type: intelligence and life expectancy are normal. Respiratory limitations due to small thorax and development of stenotic vertebral canal (peripheral neurologic deficits) may decrease the quality of life.
Recurrence: One affected parent: 50%.
If both parents are affected: 50% risk of heterozygous achondroplasia, 25% risk of homozygous achondroplasia and 25% chance of unaffected child.
De novo mutation: low recurrence risk.
Asphyxiating Thoracic Dystrophy
Prevalence: 1 in 70,000 births.
Ultrasound: Phenotypic expression varies. Characteristic features are short narrow chest with short ribs and mild to moderate rhizomelic (femur and humerus) limb shortening, which may become apparent >22 weeks’ gestation.
The condition is also referred to as Jeune syndrome.
Assoc abnorm: Renal anomalies.
Follow up: Follow-up should be standard.
Prognosis: Neonatal mortality: 60% due to pulmonary hypoplasia.
Surviving neonates have normal intelligence but rarely live beyond their teens because renal and cardiovascular problems.
Recurrence: Autosomal recessive inheritance: 25%.
Atelosteogenesis
Prevalence: 1 in 500,000 births.
Ultrasound: Severe shortening of the limbs, narrow thorax, clubfeet, dislocations of the hips, knees, and elbows.
Associated with prominent forehead, hypertelorism, micrognathia and cleft palate and ‘hitchhiker thumbs’’. The features are similar, but more severe, to those of diastrophic dysplasia.
Assoc abnorm: -
Follow up: If pregnancy continues, follow-up should be standard.
Prognosis: Lethal in utero or shortly after birth due to respiratory failure.
Recurrence: In the majority of cases (de novo mutations): no increased risk.
In the rare cases of autosomal recessive inheritance: 25%.
Campomelic Dysplasia
Prevalence: 1 in 200,000 births.
Ultrasound: Shortening and bowing of the long bones of the legs (bilateral acute femoral angulation), narrow chest, hypoplastic scapulas, large calvarium with disproportionately small face, micrognathia.
Assoc abnorm: Nuchal edema, clubfeet, hydrocephalus (due to atlanto-occipital occlusion). Polyhydramnios is common.
Follow up: If pregnancy continues, follow-up should be standard.
Prognosis: Mortality in the first year of life: 95%, due to severe laryngeotracheomalacia.
Recurrence: In the majority of cases (de novo mutations): no increased risk.
In the rare cases of autosomal recessive inheritance: 25%.
Craniosynostosis
Prevalence: 1 in 2,000 births.
Associated with advanced paternal age.
Ultrasound: 1 in 2,000 births.
Associated with advanced paternal age.
Assoc abnorm: In 90% of cases, craniosynostosis is an isolated finding.
In 10% of cases, there is an association with any one of 150 syndromes, including, Crouzon syndrome, Muenke syndrome, Saethre-Chotzen syndome, Apert syndrome, Pfeiffer syndrome
Follow up: Follow-up should be standard.
Prognosis: Newborns might have difficulties with breathing, feeding and vision.
Increased intracranial pressure, which is present in one third of the newborns, might affect intelligence and neurodevelopment. Optimal timing for surgical repair should be planned.
Recurrence: De novo mutations: no increased risk of recurrence.
Syndromic forms with positive family history: 25% and 50% risk of recurrence depending on the associated syndrome.
Diastrophic Dysplasia
Prevalence: 1 in 500,000 births.
Ultrasound: Phenotypic expression varies. Characteristic features include severe shortening and bowing
of all long bones, multiple joint flexion contractures and scoliosis, clubfeet, and abducted position of the thumbs referred to as ‘hitchhiker thumb’.
Assoc abnorm: Micrognathia, cleft palate and thickened deformed ‘cauliflower’ ears.
Follow up: Follow-up should be standard.
Prognosis: This disease is not lethal and neurodevelopment is normal.
Long-term medical problems include short stature, progressive scoliosis and joint deformities making it difficult to walk.
Recurrence: Autosomal recessive inheritance: 25%.
Ellis-Van Creveld Syndrome
Prevalence: 1 in 100,000 births.
Ultrasound: Acromelic and mesomelic shortness of limbs, postaxial polydactyly, narrow chest, ectodermal dysplasia and heart defects.
Assoc abnorm: Heart defects are present in >50% of cases: single atrium, large atrioseptal defect, aortic atresia, hypoplastic ascending aorta, hypoplastic left ventricle
Follow up: Follow-up should be standard.
Prognosis: Neonatal mortality: 50% due to pulmonary hypoplasia and cardiac problems.
The overall prognosis for affected patients is related to the presence or absence of cardiac abnormalities. Intelligence is normal.
Recurrence: Autosomal recessive inheritance: 25%.
Hypophosphatasia
Prevalence: Hypophosphatasiais an inherited disorder that affects the development of bones and teeth. It can appear any time from before birth to adulthood.
Prenatal type: 1 in 100,000 births.
Postnatal type: 1 in 10,000 births
Ultrasound: In the prebatal type there is severe micromelia, severe thoracic hypoplasia, diffuse hypomineralization (decreased echogenicity) involving all the bones except for clavicles.
Assoc abnorm: -
Follow up: If pregnancy continues, follow-up should be standard.
Prognosis: Prenatal type: lethal due to severe pulmonary hypoplasia.
Postnatal type: can appear in childhood or adulthood. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. In adults, there is premature loss of teeth and recurrent fractures in the foot and thigh bones causing chronic pain.
Recurrence: Prenatal type is autosomal recessive: 25%.
Postnatal type is either autosomal recessive or autosomal dominant: 25% or 50%
Jarcho-Levin Syndrome
Prevalence: 1 in 200,000 births.
Also referred to as spondylothoracic dysostosis and short trunk dwarfism.
Ultrasound: Fusion of several vertebral bodies and misalignment with the ribs which are also fused at the part nearest the spine. The trunk is short, but the arms and legs are of normal length.
Assoc abnorm: -
Follow up: Follow-up should be standard.
Prognosis: About 40% die in the first few months due to pulmonary hypoplasia and hypertension. After the second year of life the condition improves . Neurodevelopment is normal.
Recurrence: Autosomal recessive inheritance: 25%.
Osteogenesis Imperfecta
Prevalence: 1 in 15,000 births.
The most common are types I and IV.
Ultrasound: Spectrum of the defects characterized by fragile bones.
There are at least eight recognized forms of osteogenesis imperfecta, designated type I through type VIII with overlapping characteristic features. Type I is the mildest form and type II is the most severe; signs and symptoms of the other types fall somewhere between these two extremes.
Most cases that present prenatally are types II and III:
Type I: fragile bones, blue sclerae and progressive deafness. Ultrasonography in the second and third trimesters may demonstrate fractures of long bones.
Type II: short limbs and ribs with multiple fractures, hypomineralization of the skull.
Type III: multiple fractures, usually present at birth, resulting in scoliosis and very short stature.
Assoc abnorm: -
Follow up: Follow-up should be standard.
Prognosis: Type I: normal life expectancy.
Type II: lethal.
Type III: motor disability (kyphoscoliosis, fractures), hearing loss in adulthood.
Recurrence: De novo Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, but most infants with more severe forms of the condition (types II and III) are caused by new mutations.
Short Rib Polydactyly Syndrome
Prevalence: 1 in 500,000 births.
Ultrasound: Micromelia, short ribs with hypoplastic thorax, polydactyly (usually preaxial). There are four types of short-rib polydactyly syndrome: Type I (Saldino-Noonan): narrow metaphyses. Type II (Majewski): facial cleft and disproportionally shortened tibiae. Type III (Naymoff): wide metaphyses with spurs. Type IV (Beemer-Langer): median cleft lip and ambiguous genitalia in some 46,XY individuals.
Assoc abnorm: Heart defects, polycystic kidneys, brain malformations and intestinal atresia.
Follow up: If pregnancy continues, follow-up should be standard.
Prognosis: The condition is lethal due to severe pulmonary hypoplasia.
Recurrence: Autosomal recessive inheritance: 25%.
Thanatophoric Dysplasia
Prevalence: 1 in 10,000 births.
Most common lethal skeletal dysplasia.
Ultrasound: Severe shortening of the limbs, narrow thorax, normal trunk length and large head with prominent forehead. There are 2 types of thanatophoric dysplasia: Type I (more common): sporadic, the femurs are curved (telephone receiver). Type II (rare): sporadic, the femurs are straight but the skull is cloverleaf-shaped.
Assoc abnorm: -
Follow up: If pregnancy continues, follow-up should be standard.
Prognosis: The condition is lethal due to severe pulmonary hypoplasia.
Recurrence: No increased risk.
