Trial Information

Characterization of At-risk Population and Prognosis Factors for SACRO-coccygeal Teratoma in CURRARINO Syndrome. A Clinical, Molecular and Pathological Study.

CURRARINO syndrome (CS) (OMIM 176450) is a rare congenital disease described in 1981, as the
association of, at least, three main clinical features: typical sacral malformation
(sickled-shape sacrum or total sacral agenesis below S2), hindgut anomalies and pre-sacral
tumor. To date, neurological defects, as tethered cord and/or lipoma of the filum or the
conus, are up lighted to be as a fourth major clinical sign.In half of cases, CS is ascribed
to heterozygous mutations of the HLXB9 gene (or MNX1 gene, OMIM 142994) located at 7q36,
with an autosomal dominant mode of inheritance. The HLXB9 gene is involved in motoneurons
and caudal development of the embryo. However, genetic heterogeneity is suspected, since
patients without HLXB9 mutation harbour subtle phenotypic variations. Presently, no other
locus has been identified. The pre-sacral tumor develops in almost 80% of CS. When it is a
teratoma (30% of cases), it may turn into malignancy in 1 to 4 % of cases, according to
literature. As far as we know, no clinical, molecular or pathological marker is operational
to predict tumoral evolution and give any prognosis. Major aim of this study is to find out
any correlation between clinical signs, constitutional and somatic genetic anomalies of
HLXB9 gene and other candidate genes, and/or pathological features and tumoral evolution in
CS. Evaluation of the pre-sacral tumor evolution is based on local recurrence or distance
metastasis after surgical removal. Annual serum alpha-foeto-protein level monitoring is also
performed, as the unique marker of teratoma.This study specifically required annual clinical
examination and lumbar-sacral MRI imaging, three blood samples at inclusion and an annual
blood sample.This multicentric study will last for at least 6 years. Eighty patients will be
included and follow up for at least 3 years. Finally, this study may help identify a group
of at-risk patients for tumor development and malignant transformation if pre-sacral
teratoma. It will also help define objective clinical, radiological, molecular, pathological
and/or biological criteria for long lasting survey. In general, it may also contribute to
support hypothesis of close relationships between genes involve in oncogenesis and those
involve in embryological development.