Developmental anomalies with features of disorganization (Ds) and amniotic band sequence (ABS): A report of four cases

Abstract

Disorganization (Ds) is a mouse mutant in which heterozygotes manifest defects in various organ systems including cranioschisis, hamartomas, limb abnormalities, body wall defects, eye defects, and craniopharyngeal defects. We report four patients with developmental anomalies that are seen in amniotic band sequence (ABS) with additional anomalies that could not be explained by amniotic bands alone. The anomalies seen in our patients included facial malformation and clefting, brain anomalies (encephalocele, agenesis of the corpus callosum, holoprosencephaly), eye anomalies (anophthalmia, microphthalmia, and microcornea), and extremity and digit anomalies (talipes equinovarus, absent/hypoplastic phalanges, amputation of an extremity, syndactyly, polydactyly, and anomalous attachment of an extremity). Other systems involved include genitourinary anomalies (hydronephrosis and abnormal testes, epidydimis and seminal vesicles), and skin appendages similar to those seen in Ds mice. Presence of amniotic bands in addition to malformations not attributed to amniotic bands, were seen in three of four patients. The four patients in this report have involvement of at least four organ systems including the skin appendages that have been reported in the Ds mouse and have clinical findings that overlap the spectrum of Ds and ABS.

Human equivalent of mouse disorganization: Has the case been made?

“…Split genital papilla, in the presence of an intact body wall, and segmental duplication of the gut were not reported in any ABS/HEDs patients. Microphthalmia was not uncommon in the Ds mouse and was reported in several ABS/HEDs patients [Donnai and Winter, 1989, Case 5; Purandare et al, 2009, Cases 3 & 4]. However, in all three patients there was either severe disruption of the entire frontal brain and face, and/or direct disruption of the ocular region by bands.…”

“…Cranial defects that are not uncommon in ABS were present in a number of the cases. Several patients could be classified as having limb‐body wall defect (LBWD) as defined by Van Allen et al [1987] [Graham et al, 1981, Case 1; Donnai and Winter, 1989, cases 2 & 4; Elliot et al, 1995; Purandare et al, 2009, Case 4]. Bands and adhesions are a common feature of LBWD and Van Allen et al [1987] suggested vascular compromise as the pathogenesis for LBWD.…”

“…The above discussion is germane to the question of an ABS type of HEDs because the sign, in some cases with other malformations, that has led most authors to suggest this diagnosis for patient(s) has been the presence of one or more skin pedicles, tags, or appendages similar to those observed by Streeter [1930]. Such cases include Corona‐Rivera et al [2003], Donnai and Winter, [1989] (Cases 2–4), Elliot et al [1995], Graham et al [1981] (Case 1), Hennekam [1992], Hivnor et al [2007], Isidor et al [2009] (Cases 1–6), Kabra et al [1994], Nakamura and Nanjyo [1992], O'Driscoll et al [2008], Purandare et al [2009] (Cases 1–4), Temtamy et al [2010] (Cases 1 & 2), Ten Donkelaar et al [2002]. In some instances the authors describe connections between the appendage(s) and other body parts or the amnion [Graham et al, 1981, Case 1; Donnai and Winter, 1989, Case 5; Nakamura and Nanjyo, 1992; Korniszewski et al, 1999; Corona‐Rivera et al, 2003; Hivnor et al, 2007; Purandare et al, 2009, Cases 2 & 3].…”

“…Internal malformations that are found in patients with signs of ABS, but which are not readily explicable on the basis of disruption by amniotic bands, are the other major reason that the diagnosis of HEDs is proffered. Examples would include internal renal and genital anomalies [Donnai and Winter, 1989, Cases 2 & 6; Purandare et al, 2009, Cases 3 & 4], intracranial malformations [Donnai and Winter, 1989, Cases 4 & 6; Isidor et al, 2009, Case 5; Purandare et al, 2009, Cases 1–3], typical cleft lip/palate [Donnai and Winter, 1989, Cases 2 & 3; Hennekam, 1992; Korniszewski et al, 1999; Isidor et al, 2009, Cases 4 & 5], atypical cleft [Purandare et al, 2009], and microphthalmia [Donnai and Winter, 1989, Case 5]. Several similar cases were published prior to the proposal by Donnai and Winter [1989] that the pathogenesis might be that of HEDs [Herva and Karkinen‐Jaaskelainen, 1984; Van Allen and Myhre, 1985; Hunter and Carpenter, 1986].…”

Sirenomelia and caudal malformations in two families

“…The recurrence in this family could be explained by a recessive pattern, but no increased prevalence of consanguinity is found in sirenomelia, and in the familial reports renal anomaly or imperforate anus were described in first‐degree relatives, suggesting a dominant pattern of inheritance with low penetrance [Rudd and Klimek, 1990; Selig et al, 1993], with one asymptomatic mother [Selig et al, 1993] and a father with few symptoms [Rudd and Klimek, 1990], with narrow inter‐pediculate distance. Our preferred hypothesis then is a dominant major gene with variable expression potentially due to genetic modifier genes, environmental effects or epigenetic repercussions (diet, toxins, hyperglycemia…), as in the mouse model “disorganization” (Ds), in which there is a spontaneous mutation in an inbred strain of mice, with random occurrence of multiple defects with extreme variability in a semi‐dominant manner [Hummel, 1958; Crosby et al, 1993; Isidor et al, 2009; Purandare et al, 2009; Hunter, 2011]. The Ds gene has been located on mouse chromosome 14, but remains elusive [Crosby et al, 1993; Hunter, 2011].…”