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CHARACTERISTIC NEURAL TUBE DEFECTS AND OVERLAP IN OEIS COMPLEX AND LUMBAR SYNDROME 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical Genetics
  • Secondary Categories:
    • Clinical Genetics
Introduction:
Spinal defects are common in OEIS complex (Omphalocele, Exstrophy, and Imperforate anus, and other anomalies), aka Cloacal Exstrophy (CE), one of the Recurrent Constellations of Embryonic Malformations (RCEM). Recently, we reported clinical overlap between OEIS and LUMBAR (Lower body infantile hemangioma (IH), Urogenital anomalies, spinal cord Malformations, Bony deformities, Anorectal/Arterial anomalies, and Renal anomalies) syndrome. In particular, the spinal and neural tube defects (NTDs) in OEIS and LUMBAR are similarly distinct and rare among NTDs. The purpose of this study was to review and compare the findings in 219 cases of OEIS and 144 cases LUMBAR, and characterize the component spinal/NTDs, all of which suggest a common pathogenetic mechanism.

 

Methods:
We reviewed 219 cases of OEIS/CE [N=50 (CEK,KKN); N=34 (RH), N=135 (reported)], and 144 reported cases of LUMBAR (DWM, DHS).

 

Results:
We identified that 177/219 (81%) had spinal defects: of these, 162 of 219 (74%) had terminal myelocystoceles, lipomeningoceles, or meningoceles (all skin-covered), most with tethered cord and intradural lipoma. Agenesis/ hypoplasia of the sacrum and coccyx, and vertebral anomalies were present. Strikingly similar proportions and types of spinal defects were present in LUMBAR. 113 of 144 (78.5%) had spinal defects; closed NTDs were most common, with tethered cord (in >50%), intraspinal lipoma or hemangioma. The spinal defects included syrinx, lipomeningocele/-myelocele/-myelomeningocele. In addition, there was significant overlap in skeletal, anorectal, and genitourinary defects with these spinal defects in OEIS and LUMBAR.

 

 

Conclusion:
Terminal myelocystoceles (closed) with tethered cord and intradural lipoma, rare among isolated NTDs, are the characteristic NTD in OEIS and LUMBAR associated with sacral, anorectal, and genitourinary defects. Embryologically, these spinal defects occur at 6-7 weeks post-conception during retrogressive differentiation in secondary neurulation. OEIS and LUMBAR may be due to a failure of the neural and mesodermal tissues to become distinctly specified and spatially separated in the rapidly developing posterior portion of the embryo. Neurulation, lateral folds’ formation of the caudal-ventral body wall, growth of the urorectal septum and subdivision of the cloaca have spatiotemporal dynamics regulated by potential overlapping Wnt and planar cell polarity gene signaling pathways as well as environmental factors. In LUMBAR, the presence of segmental lumbosacral hemangiomas suggests additional genes involved in angiogenesis, upregulated by tissue hypoxia, may also contribute to the other malformations in both LUMBAR and OEIS.

 

Agenda

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