Jarcho–Levin syndrome (JLS), also called autosomal recessive spondylocostal dysostosis (ARSD), is a rare type of segmental costovertebral malformation.
Jarcho-Levin syndrome includes multiple segmentation defects of the vertebrae with abnormalities of the ribs. There could be rib fusion, malalignment or abnormal rib number. Radiological findings show abnormal segmentation of virtually every vertebrae, along with affection of ten contiguous vertebral segments at the minimum. Jarcho-Levin syndrome presents with a short trunk in proportion to height, short neck and non-progressive mild scoliosis in most affected individuals.
The spine and rib abnormalities cause other signs and symptoms of spondylocostal dysostosis. In infants this condition manifests from birth itself as small chests that don’t expand completely, often producing life-threatening complications [3]. As the lungs expand in the narrow chest, the diaphragm is forced down and the abdomen is pushed outwards. The increased intraabodominal pressure can cause an inguinal hernia, especially in male children. Neurologic complications appear to be rare.
To confirm and establish the diagnosis perform:
Once the diagnosis of Jarcho-Levin syndrome has been established in an individual, the approach listed below may be employed to determine the specific gene involved:
To establish the progress of disease in an individual diagnosed with the disorder, the following should be assessed:
The vertebral and rib malformation causes great difficulties to the patient and the treatment are most of the time conservative:
Pulmonary hypertension and cardiac failure is caused due to chronic respiratory failure due to reduced lung capacity and this most significant secondary complication. Expert management of these clinical problems is required. The parents or the care providers should be alert for the signs of inguinal hernia which is a potential complication.
Prognosis of the disease is bad as individuals either die in infancy of respiratory failure and individuals who survive with severe anomalies are very rare.
Jarcho-Levin syndrome is an autosomal recessive disorder. Mutations in at least four genes are known to cause the disorder:
Mutations in the four identified genes account for approximately 25 percent of diagnosed cases. Scientists suggest the possible role of additional genes in Notch signaling pathways.
Jarcho-Levin syndrome associated with DLL3 is most commonly encountered. 75% of the cases have been the offspring of consanguineous unions mostly of Middle-eastern or Pakistani origin, occasionally Europeans from England.
The DLL3, MESP2, LFNG, and HES7 genes play a major role in the Notch signaling pathway, which is an important pathway in embryonic development. An important function of this Notch pathway is to separate future vertebrae from one another during early development, a process called somite segmentation. Somite segmentation does not occur properly when this pathway is disturbed, resulting in the malformation and fusion of the bones of the spine and ribs seen in JLS [2].
Carrier testing for at-risk family members is possible if the disease-causing mutations in the family are known. Approximately 75% of cases have occurred in consanguineous families, generally from communities wherein cousin marriages are common. Molecular gene testing of potential patients from these high-risk areas may be helpful in identifying at-risk couples [5].
The offspring of an affected individual are obligate heterozygotes (carriers) for a disease-causing mutation. Each sibling of the affected individual’s parents is at 50% risk of being a carrier. The optimal time for determining the genetic risk, clarifying the carrier status, and discussing the availability of prenatal testing is before pregnancy. Offering genetic counseling is a must and includes discussion of potential risks to offspring and reproductive options to young adults who are already affected or are known carriers, or have a high risk of being a carrier.
Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis which is usually performed at 15-18 weeks’ of gestation or chorionic villus sampling which is usually performed at 10-12 weeks’ of gestation if the disease causing mutation is identified in the family. Fetal ultrasound can also be performed and it is a non invasive safe method [6].
Jarcho-Levin syndrome (JLS), which is also called autosomal recessive spondylocostal dysostosis (ARSD), is a rare inherited disease characterized by segmentation defects of the ribs and vertebrae. Jarcho and Levin reported the first cases in 1938 [1] [2]. Affected individuals have short, rigid necks and short midsection because of bone malformation. They are thus short statured but with normal length arms and legs. The infants born with this condition usually have a small chest causing them respiratory problems. The disorder is usually diagnosed on radiography and management includes supportive care.
Jarcho-Levin syndrome is a rare inherited disorder, were the abnormalities of vertebrae and ribs are marked. Affected individuals have short trunk in proportion to height, short neck, and mild scoliosis with narrow chest. Respiratory complication occurs due to reduced space for lungs to expand and it is usually the cause of death in these patients.
Males are at increased risk of having inguinal hernia. It is usually seen in offsprings of consanguineous partners and is diagnosed on radiology and confirmed by genetic testing.
Management includes proper care of respiratory functions and treating inguinal hernia in males. Surgery is attempted if scoliosis is significant. Prenatal genetic counseling should be undertaken to prevent the disease.