Is 1p36 deletion associated with anterior body wall defects?

Abstract

Epispadias and exstrophy of the cloaca, also known as OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects), respectively constitute the most benign and severe ends of the bladder exstrophy-epispadias complex (BEEC) spectrum. In 2009, El-Hattab et al. reported the first patient with OEIS complex associated with a chromosome 1p36 deletion. Here we report a second patient with 1p36 deletion who also has classic bladder exstrophy, supporting the possible role of genes in this region in the development of BEEC. The absence of omphalocele and imperforate anus in our patient places him toward classic bladder exstrophy while presence of spina bifida and the absence of coccyx suggest an overlap with OEIS complex. An additional differential diagnosis is the pentalogy of Cantrell in our patient as he also has a diaphragmatic hernia and an incomplete sternum. This is the second observation of a ventral midline birth defect in association with 1p36 deletion syndrome, following El-Hattab et al.'s report [2009]. The three genes (NOCL2, DVL1, and MMP23B) discussed as possible candidates are also among the deleted ones in our patient, supporting the possible role of these genes in BEEC spectrum. © 2016 Wiley Periodicals, Inc.

Prenatal findings in 1p36 deletion syndrome: New cases and a literature review

“…Details of each case are given in Table . The mean ± SD (range) term at the time of diagnosis was 19 ± 5.6 weeks of gestation, and the mean ± SD (range) maternal age was 29.2 ± 6.7 (19‐42). In all cases, the indication for an invasive procedure (CVS in four cases and amniocentesis in six) was the presence of abnormal ultrasound findings: nuchal translucency greater than 3.5 mm (n = 4), a structural brain abnormality (hypoplasic corpus callosum, n = 2), ventricular dilatation (n = 3), retrognathia suggesting a Pierre‐Robin sequence (n = 2), and a cardiac defect (n = 1).…”

“…Two cases of monosomy 1p36 displayed OEIS—indicating a possible role of genes in the 1p36 region in the development of the bladder exstrophy‐epispadias complex (BEEC). Both cases were diagnosed postnatally. Most cases of OEIS are sporadic and do not have an obvious genetic etiology.…”

“…Çöllü et al reported on another patient (from a dizygotic twin pregnancy) with bladder exstrophy. Chromosomal microarray analysis revealed a 1.77 Mb terminal deletion of chromosome 1p36 (779 727‐2 558 913).…”

“…31 However, no obvious candidate genes have been annotated within the deleted zone; hence, this case might also reflect the chance occurrence of two independent conditions. Çöllü et al 23 The maternal serum αFP level was documented in 10 cases and was elevated in eight of these (included the OEIS case, where might have been due to poor closure of the abdominal wall) ( Table 1). It remains to be established whether or not an elevated serum level of αFP (a marker of neural tube defects) is correlated with 1p36 deletion in prenatally diagnosed cases.…”

Targeted copy number screening highlights an intragenic deletion of WDR63 as the likely cause of human occipital encephalocele and abnormal CNS development in zebrafish

“…Finally, the recurrent 1p36 deletion was identified in two fetuses (P736-04 and P886-08) and is known to cause a syndrome in human patients. Neural tube defects are not associated with 1p36 deletion syndrome but have been reported (Çöllü, Yüksel,Şirin, Abbasoglu, & Alanay, 2016) and Ski knock-out mice have exencephaly (Colmenares et al, 2002), supporting SKI as a plausible candidate gene for the midline defects often seen in the syndrome (Çöllü et al, 2016). Further supporting pathogenicity, in fetus P886-08, the 1p36 deletion was accompanied with a 10q26.3 duplication, a finding consistent with an unbalanced translocation, unfortunately parental samples were unavailable for testing for a balanced t(1;10) translocation.…”