2006-06-06-14 Jarcho-Levin syndrome with caudal regression © Cuillier www.thefetus.net/
Jarcho-Levin syndrome with caudal regression
Cuillier F, MD*, Charpentier AS**, M’Lamali H***, Colbert R, MD***
* Department of Gynecology, Félix Guyon’s Hospital ** Department of Gynecology, Gabrile Martin’s Hospital *** Sonographer, Saint-Paul, Réunion Island, France
Definition: Caudal regression syndrome is a rare congenital defect characterized by the absence of the sacrum and a defect of lumbar spine. It is considered to be the most characteristic of all congenital anomalies associated with maternal diabetes mellitus.
Case report: This is a 22-year-old-woman, G2P1, referred to our unit (Gabriel Martin Hospital) at 24 weeks. During the first trimester, the triple test and nuchal translucency were not measured. Ultrasound examination revealed a single fetus in a pelvic presentation and the following ultrasound findings:
The amniotic fluid was nearly absent
The placenta was normal
The lower extremities were abnormal, in a fixed position
The length of the femurs were different
The right leg was abnormal. The right femur was very short (right femur = 15 mm and left femur = 40 mm). The right tibia was not present and the foot was malaligned. The right leg was on adduction position, coiling up the left femur.
The left leg: clubfoot.
An Arnold Chiari syndrome was diagnosed. Below the thoracic level 8, there was a complete absence of the vertebrae. Nevertheless the spine was really difficult to evaluate because the fetus was on the same position during the entire scan (the spine was posteriorly located).
A single umbilical artery was seen
The two kidneys were normal as well as the bladder
The fetus was male and the phallus seemed normal
An intraventricular septal defect was seen
The parents were counseled and they opted for an interruption of the pregnancy. After the delivery, the diagnosis of the lower extremities was confirmed and radiological examination of the skeleton revealed a complete absence of the vertebrae below the eight thoracic vertebrae. There was either a posterior fusion of some right ribs and posterior anomalies of the vertebrae segmentation. The diagnosis of spondylo-costal dysostosis was suspected. There was an atria-ventricular septal defect, a single umbilical artery and a right ureteral bifidity. The patient was informed about the Jarcho Levin syndrome, an autossomal recessive disorder.
This case confirms that «anatomical-pathologic analysis» (we prefer not to use the name «autopsy», not to scare the parents) is really important and may detected some rare syndromes, as in our case. So in the next pregnancy the parents were counseled to perform an early ultrasound examination to evaluate the fetal anatomy.
The normal right femur and the short left one
Abnormal right leg
Left tibia and left foot
Normal left leg
Left image: Note the absence of the spine below the thoracic level 8. Right image: Arnold-Chiari syndrome
Single umbilical artery and the ventricular septal defect
Radiography views showing the spine defect and the abnormal right lower limb
Synonym: caudal regression syndrome; caudal dysplasia sequence; sacral agenesis; phocomelic diabetic embryopathy.
History: The caudal regression syndrome is an exceptional poli malformation syndrome described for the first time by Geoffroy Saint-Hilaire and Hohl during the XIX century. Friedel in 1910 described the same findings as a total absence of the lumbo-sacral spine. The term of “caudal regression syndrome” was first described by Duhamel in 1961. He introduced this term to explain the spectrum of sacro-coccygeal malformations, of which sirenomelia was thought to be the severe form. According to the literature review (in 1998), more than 250 cases have been described.
Prevalence: Caudal regression syndrome has been observed in only 0.1-0.25:10.000 pregnancies. But the caudal regression syndrome has been observed in only 2/1000 pregnancies complicated by diabetes mellitus. So the relative risk for caudal regression syndrome is increased 250-fold in infants of diabetic woman. Nevertheless, an embryo affected by caudal regression syndrome, are often loss as an early miscarriage.
Etiology: The caudal regression syndrome is often sporadic. This anomaly is not thought to be hereditary, but the recurrent risk is higher in diabetics’ women. If the woman diabetes is severe, the caudal regression syndrome malformation is also more severe.
Despite intensive investigation, the teratogenic factors in the pregnancy complicated by diabetes mellitus have not been precisely defined. Mills et all declared that anomalies in the offspring of women with diabetes mellitus could be related to glucose control. But insulin and hypoglycemia don’t have a teratogenic role. Animals studies have showed either that physic agents, elevated temperature, hypothermia, traumatism, X rays, chemotherapy, lithium, sulfamide, actinomycin, strychnine, arsenic and saponins can be responsible. Contrary, alcoholism is not responsible. Nutritional deficiency as zinc, hypovitaminosis-A should be responsible. Nevertheless, familial cases have been described, suggesting an autosomal dominant inheritance. The chromosome 6 would be responsible.
Pathogenesis: Classically, it said that caudal regression syndrome results from a defect in the mid-posterior axis mesoderm of the embryo and originates before the 4th weeks, causing an absence or dysplasia of the sacrum and the other associated anomalies. Nevertheless according to Kubryk, two mechanism can be responsible of caudal regression syndrome:
Absence of development of the caudal bud with mesenchymatisation anomaly. The caudal regression syndrome resulted form the absence of development of the mesoblastic caudal bud.
Accentuation of the normal processus of appendices caudal regression (with last somites disparities). The consequences are that disruption of the maturation of the caudal portion of the spinal cord complex prior to 4th weeks, leading to motricity deficits and neurologic impairment, varying from to incontinence of urine and feces to complete neurologic loss.
Sonographic findings: The sonographic findings of caudal regression syndrome are variable and depend on the extent and the severity of the defects. Severe forms of caudal regression syndrome may include sacral agenesis, vertebral and spinal cord agenesis, pelvic deformation and hypoplasia, femoral hypoplasia, talipes equinovarus, muscular atrophy of the lower extremities. Flexion, contractures of the knee and webbing can also be present.
A complete absence of the sacrum: is often associated with abnormalities of the lumbar spine and the lower extremities.
Decreased movement of the legs is frequently observed.
Simple anomalies of the sacrum: without associated minor defects. Minor forms may not be recognized until childhood.
Nevertheless, the most typical findings are the absence of vertebrae, the shield like appearance of the fused or approximated iliac wings and the decreased interspace between the femoral heads.
Implications for targeted examinations: About sonographic study:
During the first trimester: we must think about caudal regression syndrome when crow-rump length is shorter and when there is an absence of fetal movement. However the diagnosis is frequently difficult to perform during the first trimester, because the sacrum is not ossified. Nevertheless a short crown-rump-length and abnormal appearance of the yolk sac are have possible clues of caudal regression syndrome. Then, often, during other initial scan, there is a possible lag in growth of the fetus. Transvaginal scan can detect either the lack of movement of the fetal thighs after 10 weeks and later the fixation at a 50° angle (corresponding to «the frog–leg position»). Nevertheless the caudal regression syndrome will be seen better at 16-18 weeks and became so prominent that it would have been hard to miss it even by abdominal scan.
During the second trimester: a "Bouddha position" is classically evocated. Houfflin et al (1996) described a femoral "V" was associated with sudden interruption of the spine. The level of maternal-fetal-protein is normal. It is only elevated if there is a dysraphia or neural tube defect.
Sirenomelia: The Mermaid syndrome is a different entity and was considered for many years to be the more severe form of caudal regression syndrome, but recent evidence suggests that these two conditions are separate entities. Synonyms are symmelia or ectrourie. Duhamel realized the first description on 1960. The incidence is 0.15:10.000 (2.7 boy/ 1 girl). There is fusion of the inferior members associated with digestive anomalies, vertebrae anomalies, and bilateral agenesis and dysgenesis or hypoplastic renal arteries. The ultrasound diagnosis reveals an absence of visualization of the tibia and perone with one femur. There is anhydamnios and the Doppler shows abnormal vascularization of the inferior part of the fetus. Contrary to caudal regression syndrome, there is no correlation with diabetes mellitus. But monozygote twins, Cocaïn abuse (vasoconstrictor effect) and vascular malformation are often responsible of sirenomelia VATER syndrome, Currarino triad: also Ano-rectal, Sacral and Presacral (ASP) syndrome is totally different. This complex malformation associates ano-rectal malformation, sacral bony defect and a presacral mass.
Associated anomalies: The more severe form of caudal regression syndrome is characterized by:
Anomalies of the central nervous system: because there is caudal vertebrae agenesia or hypoplasia up to lumbar or thoracic spine. Hemi-vertebrae, spina bifida with meningocele or myelomeningocele can be present. Chih-Ping described the first case of concomitant alobar holoprosencephaly and CRS (It occur in pregnancies with poor maternal metabolic control).
Anomalies of the muscular-skeletal system: Abnormal rotation; Luxation of the hips and the thick; Rocker bottom; Atrophy; etc.
Anomalies of the genital-urinary system: are severe. vulvar agenesia or hypoplasia; asexual state; uterine agenesia, kidney agenesia; bladder agenesia; single umbilical artery.
Anomalies of the gastro-intestinal system: rectal agenesia; anal imperforation
Anomalies of the respiratory system
Prognosis: The prognosis depends essentially on the severity and extent of spinal enrollment and associated malformations. The CRS severity is correlated with the Renshaw classification:
Type I: Partial or total sacral agenesia, but unilateral
Type II: Partial sacral agenesia, but bilateral and symmetrical.
Type III: Total sacral agenesia with variable lumbar anomaly, with iliac wing attached to the last lumbar vertebrae.
Type IV: Total sacral agenesia with +- lumbar anomaly and iliac wings fissioned behind the last vertebrae.
The minor form: as coccyx agenesia are without functional repercussions. The urinary retentissement as neurological bladder can be theorically sign of the sacral agenesia.
The major form: are the type III and IV. They have a dramatic prognostic. The perinatal death is frequent. If the baby survives, the neurological impairment is very important. The functional deficit can associate paraplegia, anal or urinary incontinence. The sever form with thoracic vertebrae insult are incompatible with life.
Management: If caudal regression syndrome is discovered during the pregnancy, the parents must be informed and pregnancy interruption can be proposed. The case described by our team, confirms that the caudal regression syndrome may detected antenatally by ultrasound, but should have been discovered earlier than during the end of the second trimester. If the interruption is not required, the majority of the surviving baby requires severe urological, orthopedic interventions. The fetal prognostic is dramatic. Moreover, it is really important to obtain from parent, the authorization to perform a fetal anatomical-pathologic analysis, because as in our case, we can find some exceptional associated Jarcho-Levin syndrome, an autosome recessive disorder.
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9- 2005-08-22-15 Jarcho-Levin syndrome © Cuillier www.thefetus.net/10- 2006-05-08-11 Jarcho-Levin syndrome © Cuillier www.thefetus.net/