Case report:The prenatal diagnosis of Jarcho-Levin syndrome type I has been made in families at risk, by radiographs. We describe the diagnosis using ultrasonography in a 17-week-old fetus with no positive family.
This was the ninth pregnancy of a 38-year-old woman, with no history of radiation or teratogenic exposure during early pregnancy. The family history did not reveal any congenital anomalies or hereditary diseases. This pregnant woman, non-consanguineous, gravida 9, para 8, underwent a first routine ultrasound at 16 weeks of gestation. Prior maternal serum screening for alpha-fetoprotein, hCG and UE3 was unremarkable. The images revealed a shortened spine, vertebral disorganization and spina bifida without any renal anomalies.
At 17 weeks, transverse view of the fetal head. We can see bilateral ventriculomegaly.
There is severe disruption of the normal spine with kyphoscoliosis and segmentation abnormalities.
3-D reformatted CT scan
Postnatal anterior and lateral views. Note the characteristic short neck and chest
- Severe disorganization of the spine with intact skin covering nearly its whole length was noted.
- A grossly distorted thoracic and lumbar spine with marked kypho-scoliosis and multiple segmentation anomalies were observed.
- There was gross abnormal alignment of the vertebral bodies on both coronal and longitudinal views with several hemi vertebrae and ribs fanning out in a crab-like fashion due to the posterior fusion of the ribs.
- A small chest: the thorax appeared small in relation to the abdomen.
- Limb lengths were within normal ranges for gestational age.
An amniocentesis was performed. Chromosome analysis of amniotic-fluid cells showed a normal karyotype.
In an attempt to clarify the nature of the spinal deformity, three-dimensional ultrasound of the fetal spine was performed. Although there was no previous history, based on the ultrasound findings Jarcho-Levin syndrome was suspected. The parents were informed about the findings and the associated poor prognosis. After genetic counseling, the patient elected to terminate the pregnancy at 18 weeks of gestation.
The postmortem examination showed a male fetus with severe kyphosis of the spine, disorganization and bilateral fusion of several malformed vertebral bodies and ribs resulting in a small thorax and shortened neck. Biometry was adequate for gestational age and no other malformation was found. The skull and long bones were normal. External examination of the fetus demonstrated a short trunk and neck and kypho-scoliosis. The spina bifida was confirmed. The examination also revealed fusion of the ribs with each other and the thoracic vertebrae, severe kypho-scoliosis and a small chest.
Radiological findings confirmed multiple vertebral deformities, hemi-vertebrae and abnormal ribs. All of these findings were consistent with the Jarcho-Levin syndrome. Fetal high-resolution spiral computed tomography (CT-scan) also showed the hemi vertebrae and fusions.
Genetic counseling was offered to the couple for an autosomal recessive mode of inheritance. These findings were discussed with the parents and plan made to assess any subsequent pregnancy with ultrasound.
History: Jarcho-Levin syndrome is a rare entity. Jarcho and Levin described their first case in 1938 2. Over 120 cases of Jarcho-Levin syndrome have been reported since 1938, and only a few cases have been diagnoses prenatally 3.
Coma and Castro (1979) made the first reported antenatal diagnosis by using radiography in at-risk patients. They made the diagnosis by identifying the crab-like deformity of the chest in the third trimester.
Prenatal ultrasound diagnosis of Jarcho-Levin syndrome was first established by sonography in 1987 and again in 1989 when sonographic criteria for this condition were described. The most characteristic sonographic features were abnormal alignment of the vertebral bodies and posteriorly fused ribs 4. Those reports have described the usefulness of prenatal sonographic diagnosis in families known to be at risk as well as in those with no positive family history.
Apuzzio (1987) realized an antenatal diagnosis at 22 weeks of gestation.
The sonographic features noted were abnormally spaced vertebrae, rib flattening and an abnormally shaped chest with normal limb biometry 5.
Tolmie et al (1987) made an antenatal diagnosis of Jarcho-Levin syndrome at 20 weeks of gestation in a couple with a previously affected child. They opted for termination of pregnancy 3.
Romero et al (1988) realized an antenatal diagnosis of Jarcho-Levin syndrome at 23 weeks of gestation.
Marks et al (1989) reported three cases of Jarcho-Levin syndrome, diagnosed in the third trimester, presenting with unpaired and poorly formed vertebrae, irregularly shortened spine, indistinct and joined posterior ribs and short thorax 3.
There have been a number of reports of prenatal detection of the Jarcho-Levin syndrome using ultrasound in the second trimester and a few during the first trimester.
To the best of our knowledge, there are only four studies reporting the prenatal diagnosis of Jarcho-Levin syndrome in patients not known to be at risk for the condition, although just only one made a precise diagnosis in first trimester 4.
Eliyahu et al (1997): described four cases of Jarcho-Levin syndrome- diagnosed in the first trimester (at 12 weeks of gestation) in the same family. It was an Arab family known to be at a high risk for the disease. Transvaginal ultrasound examination performed at 12 weeks found marked vertebral anomalies 6.
Hull (2001): described a case of Jarcho-Levin syndrome- diagnosed with a combination of three dimensional ultrasound and measurement of nuchal thickness allowed successful detection of recurrent Jarcho-Levin syndrome at 12 weeks. These authors proposed the use of 3-D ultrasound to explore the spinal abnormalities in families at a high risk of Jarcho-Levin syndrome in order to obtain an integrated picture of the anatomic spinal relationships 2.
Kauffmann et al (2003): described the case of a severe prenatal Jarcho-Levin syndrome that was diagnosed by ultrasound examination during the first trimester. It was the first case diagnosed during the first trimester of pregnancy in a family with no previous medical history of Jarcho-Levin syndrome 3.
Holgado et al (2005) described another case of antenatal Jarcho-Levin syndrome that was diagnosed at 20 weeks 4.
Prevalence: Jarcho-Levin syndrome is a rare congenital disease in which no clear single etiology has been established. Cases may be sporadic of familial, with both autosomal dominant and autosomal recessive modes of inheritance reported 4. Males and females are affected with equal frequency 3.
Jarcho-Levin syndrome is a very rare syndrome, but more frequent in people of Puerto Rican descent. So this syndrome is found more frequently in people of Spanish origin and their descendants. In a review of the literature, more than 135 cases are described 3.
Souka (1998) have reported increased nuchal translucency thickness in Jarcho-Levin syndrome fetuses 7.
Etiology: The mode of inheritance is believed to be autosomal recessive. Although the precise genetic basis of Jarcho-Levin syndrome has not yet been elucidated, it seems likely that mutation in the development genes or alterations in the regulating transcription factors are responsible. The gene DDL3 mapped to the 19q13.1-q13.3 region has recently been found to be responsible for some cases of spondylocostal dysostosis 3.
Pathogenesis: Jarcho-Levin syndrome or spondylo-costal dysplasia has been subdivided into two types 3:
- Type I: is inherited with an autosomal recessive pattern and is a severe form. It often occurs in families of Puerto Rican descent. It is characterized by severe involvement of the spine and generally causes respiratory failure and death in the affected children by 15 months of age. It can be diagnosed in utero.
- Type II: is inherited with an autosomal dominant trait and is a milder form. It is found most often in Caucasians. It is characterized by milder involvement and is associated with nearly normal longevity. It cannot be diagnosed in utero.
Sonographic findings: The main features of Jarcho-Levin syndrome are:
• Dwarfism with a very short thorax,
• ‘Fan like’ or ‘crab like’ rib cage anomalies due to posterior fusion and anterior flaring of the ribs,
• Multiple vertebral segmentation defects.
Associated anomalies include:
• Spina bifida
• Club feet
• Frequent neural tube defects
• Urinary tract and renal abnormalities
• Anal atresia and
• Cleft palate
The lack of a clear genetic marker for Jarcho-Levin syndrome has placed reliance on imaging techniques for prenatal diagnosis. Prenatal diagnosis of Jarcho-Levin syndrome or spondylo-thoracic dysostosis is possible using fetal ultrasound, but requires a high level of suspicion and definitive diagnosis may be delayed well into the second trimester or be made on postmortem autopsy as in our case. Three-dimensional ultrasound has been shown to be helpful in the clarification and delineation of both the normal and abnormal spine 3.
Implications for targeted examinations: Jarcho-Levin syndrome should be suspected when spinal disorganization is associated with an abnormal chest configuration.
Differential diagnosis: The differential diagnosis of spinal disorganization in a fetus includes: 3
Costo-vertebral segmentation defect with mesomelia (COVESDEM association): is characterized by:
- Spondylo-costal dysplasia
- Dyssegmental dysplasia: is characterized by severe micromelia, with extreme shortening of all segments of the extremities and occipital cephalocele. Crab-like appearance of the chest is lacking.
- Spondylo-epiphyseal dysplasia: is characterized by severe platyspondyly (flattening of vertebral bodies). Hemivertebrae are absent. Ovoid shape of the vertebral bodies is possible. Severe dwarfism is not seen and the limbs may be or not be shortened. The thorax is bell-shaped in the antero-posterior projection, but the crablike morphology is lacking.
- VACTERL association is characterized by:
• Vertebral anomalies
• Atresia or fistula tracheo-oesophageal
• Cardiac anomalies: generally a ventricular septal defect.
• Radial limb dysplasia: including preaxial polydactyly, syndactyly, radial hypoplasia, thumb dysplasia.
• Mesomelic dysplasia: particularly of the upper extremities.
• Costo-vertebral segmentation defects: hemivertebrae, vertebral fusion, butterfly vertebrae
• Facial abnormalities: hypertelorism, depressed nasal bridge, large upper lip.
Associated anomalies: The following anomalies have been reported:
• Microcephaly; prominent occiput
• Triangular opening of the mouth,
• Cleft palate
• Spina bifida occulta; lordosis
• Abdominal wall defect;
• anal defect
• Long arms with syndactyly or camptodactyly
Prognosis: Jarcho-Levin syndrome commonly leads to respiratory insufficiency and death during the first years of life, usually by 15 months of age. The severe form of Jarcho-Levin syndrome is considered a uniformly lethal condition.
Management: The precise prenatal diagnosis of ultrasound detected skeletal dysplasia is often difficult. The confidence of prenatal diagnosis is strengthened when a couple have already had one or more offspring affected with an identified problem, since the likelihood of a couple being carriers for more than one form of skeletal dysplasia is extremely low.
3-D ultrasound imaging should be offered if available. Some authors suggest that post-natal high–resolution spiral CT-scan could complement the radiological examination for a better description of the thoracic and costal defects 3.
If a prenatal diagnosis of type I Jarcho-Levin syndrome is made before viability, the option of pregnancy termination should be offered to the parents 8-9. Our case illustrates the importance of an accurate early ultrasound examination in order to detect an increasing number of rare congenital syndromes. An accurate early diagnosis of uncommon syndromes such as Jarcho-Levin syndrome is no longer confined to at-risk families.
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