Case of Complex Craniofacial Anomalies, Bilateral Nasal Proboscides, Palatal Pituitary, Upper Limbs Reduction, and Amnion Rupture Sequence: Disorganization Phenotype?

Abstract

We report a case of a dizygotic twin with complex abnormalities of head, body, and limbs. The anomalies include the following: lateral and midline cleft upper lip, ectopic palatal pituitary, natal teeth, bilateral nasal proboscides with an absent nose, left microphthalmia with conjunctival-lined cyst, right ocular dysgenesis, bilateral retinal dysplasia, platybasia with skull asymmetry, hydrocephalus secondary to aqueductal atresia, brain hemispheric asymmetry with a parietal-occipital cortical flap, agenesis of posterior corpus callosum, absence of the olfactory nerves and left anterior cerebral artery, leptomeningeal and intraventricular heterotopias, right radial longitudinal terminal meromelia with constriction rings of fingers, partial syndactyly of the third and fourth left fingers, dorsiflexed great toes and pes equinovarus bilaterally, and multiple skin tags with a sacral appendage. Additionally, this twin's placental disc and extraplacental membranes were devoid of amnion. We regard these anomalies as a possible expression of the human homologue of the disorganization phenotype or another gene mutation. Nevertheless, an abnormality of blastogenesis with early damage to organizing tissues of the frontonasal region and limbs, or a vascular disruption, cannot be excluded. Early amnion rupture sequence (possible extraamniotic pregnancy with amniotic bands, limb reduction defects with Streeter bands, and multiple skin tags tapering into amniotic bands) was also present in this case, and may have acted as a contributing factor.

Human tail

“…The association between ABS and hydronephrosis or hypopigmented retina, as observed in our patient, has been reported previously (Stanek et al, 2001). Whether liver calcifications, first described in our case, also consist of a feature of the syndrome remains to be elucidated.…”

“…Amniotic band syndrome (ABS) presents with a broad spectrum of malformations characterized by asymmetry and polymorphism ( considerable discussion in the genetic literature about the potential overlap of ABS and a syndrome similar to the autosomal dominant mouse mutant 'Disorganization,' which has come to be known as the 'Disorganization-like syndrome' (Robin and Nadeau, 2001;Stanek et al, 2001;Isidor et al, 2009). That syndrome presents with a huge spectrum of structural birth defects including mirrorimage limb duplications and hamartomatous skin pedicles; limb abnormalities resembling the band-derived malformations of ABS, as well as neural tube defects, and tails, have also been described (Robin and Nadeau, 2001;Isidor et al, 2009).…”

A Rare Left-Sided Abdominal Wall Defect

“…However, there was no autopsy or microscopic examination. Early amnion rupture sequence (ARS), which is the result of a rupture of the amniotic membrane in the first trimester, may lead to a complex variety of anomalies (6), including limb and body wall defects (2,5). The defect in our patient may well be an isolated form of ARS.…”

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

“…Luengo et al 2004 postulated that Ds constitutes a polytopic effect of blastogenesis since their patient had malformations involving all germ layers in different organ systems and propose that the pathogenic event occurred during blastogenesis affecting various progenitor fields. Stanek et al 2001 proposed the consideration that a genetic defect either predisposed to disruption or led directly to abnormalities such as those described in the four patients in this report. A Ds gene defect could be one possible mechanism.…”

“…Robin et al 1997, Stanek et al 2001, Korniszewski et al 1999, Teebi and Eliott 1996, Rosenberg et al 2002, Onal et al 2005, Hivnor et al 2007, Datta and Datta 2003, Corona‐Rivera et al 2003, ten Donkelaar et al 2002, Kabra et al 1994, Hendrick et al 1986, Hennekam 1992, Van Langen and Hennekam 1994, and Lin 1991…”