Coming together for blastogenesis

Sirenomelia and VACTERL association in the offspring of a woman with diabetes

“…In fact, with the assumption of a single dysmorphogenetic cause acting in the present family, the same factor/event possibly recurring in slightly different moments and/or intensities of action during blastogenesis or early organogenesis generated apparently distinct malformation patterns in the two pregnancies: the first one showing an axial mesodermal deficiency exclusively affecting the caudal pole (i.e., sirenomelia), the second one manifesting multiple polytopic field defects involving the mid‐body (i.e., VACTERL). This phenomenon is in line with the general opinion that the same “agent” capable to perturb blastogenesis may have different outcomes, such as sequences, field defects, associations or syndromes, and this depends on the particular distribution, timing and duration of action of the “agent” itself [Wilson, 2003]. Accordingly, in our family, it could be speculated that a limited number of morphogens regulating the development of various structures in early embryogenesis interacted with an intrinsic (i.e., mutation) and/or extrinsic (i.e., teratogen) pleiotropic factor in a dynamically and partly stochastically manner, thus resulting in diverse although ontogenetically related malformations.…”

Holoprosencephaly and limb reduction defects: A consideration of Steinfeld syndrome and related conditions

“…Animal studies have shown this, including mutations in Gli2 and in the digenic combination of Gli2 and Gli3 [Kim et al, 2001; Arsic et al, 2002; Gillick et al, 2003]. Defective blastogenesis has been put forth as a possible mechanism for the association of HPE with VATER/VACTERL [Hersh et al, 2002] and situs inversus [Gilbert‐Barness et al, 2001], although more specific pathogenetic events remain largely unknown [Wilson, 2003]. A recessive murine mutation for sonic hedgehog ( Shh −/−) has been associated with HPE and severe distal anterioposterior limb deficiencies [Chiang et al, 2001].…”