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.

• Pain

  A 24-year-old woman presented to neurosurgical consultation for chronic back pain. The patient was long term in wheelchair for vertebral deformity. She was the third child of first-degree consanguineous parents. [ncbi.nlm.nih.gov]

  'I am in daily pain but luckily my pain threshold is high,' she explained. 'I try not to take medication unless really necessary. 'I come home with pains and aches, but I believe dancing has kept my body limber and healthy. [dailymail.co.uk]

  Paresthesias, sensibility disorders, pain, muscular atrophy, paresis, spastic paralysis and perfusion disorders can exist. The disease is progressive. The described case is unusual, because of coexistence of Jarcho-Levin syndrome and syringomyelia. [stary.lf2.cuni.cz]

  ‘I am in daily pain but luckily my pain threshold is high,’ she explained. ‘I try not to take medication unless really necessary. ‘I come home with pains and aches, but I believe dancing has kept my body limber and healthy. [healthmedicinet.com]

• Recurrent Respiratory Infections

  Management should be from the basic neonatal care to prevention and immediate treatment of recurrent respiratory infections. Spinal surgical intervention to improve the thoracic volume and hence decrease the pulmonary restriction has been tried. [ncbi.nlm.nih.gov]

  Infants born with this condition typically died early in life due to recurrent respiratory infections and pneumonia due to their restricted thorax. [en.wikipedia.org]

  Infants born with this condition typically died early in life due to recurrent respiratory infections and pneumonia due to their restricted thorax. [3] [5] [16] Recently, a report [12] has documented that actual mortality associated with STD is only about [wikidoc.org]

  As these patients have recurrent respiratory infections, perioperative assessment and management of these complications is of prime importance. [6] Cyanosis while crying in the absence of cyanotic heart disease may be seen due to collapse of the trachea [ijaweb.org]

  The majority of patients with this syndrome die early during the infancy period due to recurrent respiratory infections and respiratory failure secondary to thoracic small volume. [omicsonline.org]

• Limited Chest Expansion

  The neonate had classical features of this syndrome including vertebral segmentation defects, typical costo-vertebral fusion defects and scoliosis resulting in small thoracic volume and limited chest expansion; all consistent with a clinical diagnosis [jcnonweb.com]

• Heart Failure

  Reduced lung capacity also increases the risk of heart failure another life-threatening complication. Despite the potential for serious complications, most individuals with spondylocostal dysplasia live until adulthood. [rarediseases.org]

• Continuous Murmur

  Singla, drviveksingla98{at}gmail.com Statistics from Altmetric.com Description A 2-year-old female presented with asymptomatic continuous murmur. [casereports.bmj.com]

• Low Set Ears

  We report the case of a one-day-old female baby with a short trunk, short neck, low hairline, apparently long limbs, protuberant abdomen, mild midfacial dysmorphism, low-set ears, and a high-arched palate. [ncbi.nlm.nih.gov]

  Head circumference was 35 cm, short stature (length is 37 cm), short neck, anteverted nares and dysmorphic features (low-set ears, hypertelorism, high-arched palate, short upper segment). [lungindia.com]

• Large Anterior Fontanels

  At the same time, we observe a malformation syndrome combining: a bulging forehead, a triangular face, large anterior fontanel, small ears, low-set and malformed short neck, short trunk, thoracolumbar scoliosis and a right parietal hernia (Spiegel hernia [omicsonline.org]

• Spastic Paralysis

  Paresthesias, sensibility disorders, pain, muscular atrophy, paresis, spastic paralysis and perfusion disorders can exist. The disease is progressive. The described case is unusual, because of coexistence of Jarcho-Levin syndrome and syringomyelia. [stary.lf2.cuni.cz]

  […] ataxia Charlevoix-Saguenay type Detection of mutations c.6594delT and c.5254C>T in the SACS gene Spastic paralysis, infantile onset ascending NGS and Sanger Sequencing of the ALS2 gene Spastic paraplegia 10, autosomal dominant Sanger sequencing of the [pentacorelab.hu]

To confirm and establish the diagnosis perform:

• A survey of the entire skeleton radiologically to look out for other skeletal anomalies.
• A thorough physical examination, ultrasound imaging of the heart, abdomen, and renal tract.
• Screening of the family history with specific attention to history of affected siblings and parental consanguinity.

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:

• Radiographic phenotype: Based on radiographic appearance of the spine and the ribs, diagnostic differentiation could be achieved between the subtypes.
• Molecular genetic testing

To establish the progress of disease in an individual diagnosed with the disorder, the following should be assessed:

• If there is tachypnea or feeding difficulties, check for the respiratory function as there could be respiratory insufficiency.
• Exclude other anomalies (Cardiac, renal, etc.)
• Examine the male child for the presence of inguinal hernia.
• Do genetic consultation.

The vertebral and rib malformation causes great difficulties to the patient and the treatment are most of the time conservative:

• Treatment of acute respiratory distress and chronic respiratory failure the patient is given respiratory support; the intensive care is given if needed.
• Inguinal hernia should be treated.
• If scoliosis is significant surgical intervention is given [4].
• Secondary complications must be prevented.

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:

1. Mutations of DLL3 gene produce SCDO type 1
2. Mutations of MESP2 gene produce SCDO type 2
3. Mutations of LFNG gene produce SCDO type 3
4. Mutations of HES7 gene produce SCDO type 4

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].

• At conception, there is 25% chance of each sibling of an affected individual to be affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and also not a carrier.
• The risk of an unaffected sibling to be a carrier is 2/3.
• Heterozygotes i.e. carriers are asymptomatic.

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.

1. Jarcho S, Levin PM. Hereditary malformations of the vertebral bodies. Bull Johns Hopkins Hosp 1938, 62: 216-226.
2. Karnes PS, Deborah D, Berr SA, Pierpont MEM. Jarcho-Levin syndrome: four new cases and classification of subtypes. Am J Med Genet 1991 Sep 1; 40(3): 264-70.
3. Romero R, Ghidini A, Eswara MS, Seashore MR, et al. Prenatal findings in a case of spondylocostal dysplasia type I [Jarcho-Levin syndrome]. Obstet Gynecol 1988 Jun; 71 (6 pt 2):988-991.
4. Aburakawa K, Harada M, Otake S. Clinical evaluations of the treatment of scoliosis. Trauma and Orthopaedic Surgery. 1996;39:55–62.
5. Tolmie JL, Whittle MJ, McNay MB, Gibson AAM, Connor JM. Second trimester prenatal diagnosis of the Jarcho-Levin syndrome. Prenat. Diagn 1987 Feb;7(2): 129–34. 
6. Eliyahu S, Weiner E, Lahav D, Shalev E. Early sonographic diagnosis of Jarcho-Levin syndrome: a prospective screening program in one family. Ultrasound Obstet Gynecol. 1997 May;9(5):314-8