Despite observation of multiplex nonsyndromic NTD cases in multigenerational NTD families as seen in 17 US and 14 Dutch families with more than 1 NTD-affected person, there are other NTD cases that are simplex and sporadic as seen in identical twins with lumbosacral lipomyelomeningocele with no known familiar history of NTDs [201, 202]. This suggests that NTDs have a multifactorial genetic etiology.