Prune Belly Sequence Research Articles

Secuencia de Prune Belly: a propósito de un caso

Antecedentes: La secuencia Prune-Belly es un trastorno genético que se caracteriza por una tríada que incluye deficiente musculatura de la pared abdominal, anomalías urogenitales y criptorquidia bilateral. Suele acompañarse de malformaciones asociadas. La aproximación quirúrgica debe reservarse para aquellos pacientes con complicaciones severas.Resumen del caso: Se presenta el caso de un neonato de sexo masculino con agenesia de la musculatura de la pared abdominal, displasia renal multiquística y criptorquidia bilateral, que es transferido de un hospital básico del oriente ecuatoriano y que durante su hospitalización se le sostuvo con un manejo conservador.Conclusiones: El abordaje de la secuencia de Prune-Belly, debe ser multidisciplinario por su frecuente asociación con otras malformaciones; el diagnóstico prenatal cumple un rol fundamental en la detección precoz de anomalías severas.

R179H mutation in ACTA2 expanding the phenotype to include prune‐belly sequence and skin manifestations

Mutations in ACTA2 (smooth muscle cell-specific isoform of α-actin) lead to a predisposition to thoracic aortic aneurysms and other vascular diseases. More recently, the ACTA2 R179H mutation has been described in individuals with global smooth muscle dysfunction. We report a patient heterozygous for the mutation in ACTA2 R179H who presented with megacystis at 13 weeks gestational age and, at birth, with prune-belly sequence. He also had deep skin dimples and creases on his palms and soles, a finding not previously described but possibly related to ACTA2. To our knowledge, this is the first report of the R179H mutation in ACTA2 in a child with prune-belly sequence. We think the R179H mutation in ACTA2 should be included in the differential diagnosis of individuals presenting with the sequence without an identified mechanical obstruction. Furthermore, as ACTA2 R179H has been reported in patients with severe vasculomyopathy and premature death, we recommend that molecular testing for this mutation be considered in fetuses presenting with fetal megacystis with a normal karyotype, particularly if the bladder diameter is 15 mm or more, to allow expectant parents to make an informed decision.

Unilateral agenesis of the abdominal wall musculature: An early muscle deficiency

Prune-belly sequence (PBS) usually results from early urethral obstruction. In rare cases, PBS seems to be due to a faulty primary development of the parietal mesenchyme leading to underdevelopment of the abdominal wall musculature, and disorganization of the smooth muscles in the urinary tract. We report on two patients with segmental, unilateral wall musculature deficiency associated with homolateral agenesis of ribs. One patient also had hemivertebrae and the other one ipsilateral diaphragmatic eventration and aplasia cutis. This combination of anomalies may represent a localized deficiency in the development of somitic mesoderm mesenchyme during early embryogenesis.

DNA hypomethylation, transient neonatal diabetes, and prune belly sequence in one of two identical twins

One known genetic mechanism for transient neonatal diabetes is loss of methylation at 6q24. The etiology of prune belly sequence is unknown but a genetic defect, affecting the mesoderm from which the triad abdominal muscle hypoplasia, urinary tract abnormalities, and cryptorchidism develop, has been suggested. We investigated a family, including one twin, with transient neonatal diabetes and prune belly sequence. Autoantibody tests excluded type 1 diabetes. Microsatellite marker analysis confirmed the twins being monozygotic. We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. The loss of methylation on chromosome 6q24 and elsewhere may indicate a generalized maternal hypomethylation syndrome, which accounts for both transient neonatal diabetes and prune belly sequence.

The Type and Frequency of Fetal Renal Disorders and Management of Renal Pelvis Dilatation

Although fetal renal anomalies are frequently detected by prenatal ultrasonography, pre- and postnatal follow up of these disorders is not standardized. The investigators determined the incidence of the most common renal abnormalities seen in their ultrasound unit and correlated the presence of fetal renal pelvic dilatation (RPD) with the need for postnatal surgery in 342 prospectively studied fetuses who had isolated renal abnormalities and were followed from 3 months to 10 years. RPD was defined as an anteroposterior renal pelvis measurement of 4 mm or more at less than 33 weeks gestation or 7 mm or more afterward. Two thirds (227 of 342) of fetuses had RPD as their major sonographic finding. Obstructive lesions requiring surgical treatment were present in 60 fetuses (26% of all RPD cases), and the remainder had nonobstructive lesions that either resolved spontaneously or remained stable and did not require surgery. Approximately 70% of fetuses with obstructive and 77% with nonobstructive lesions were male. Other relatively frequent abnormalities included multicystic dysplastic kidney (10.5%), urinary tract duplication malformations (9.4%), and reflux (8.2%). The other category included bladder outlet obstruction, prune belly sequence, pelvic or horseshoe kidney, and bladder extrophy. Average RPD values were 11 mm in fetuses with nonobstructive conditions and 23 mm in those with obstruction. Ninety-five percent of fetuses with obstructive RPD underwent voiding cystourethrography (VCUG) and 92% had renal scintigraphy. VCUG demonstrated vesicoureteral reflux in 23% of these cases, and the renal perfusion scan showed urinary stasis in 96%. VCUG also was performed in 74% of fetuses with nonobstructive RPD but demonstrated reflux in only 4%. Among the 29% of nonobstructed fetuses who had a renal perfusion scan, 49% had urinary stasis. An obstructive process was identified in 10% of fetuses with a RPD of 6 to 10 mm (no fetuses with maximum RPD less than 6 mm required postnatal surgery); these fetuses accounted for approximately one fifth of the postnatal surgeries. Obstruction was also found in 27% of fetuses with a RPD of 11 to 20 mm (33% of all surgeries) and nearly 70% with a RPD exceeding 20 mm (48% of all surgeries). The overall ratio of obstructive to nonobstructive disorders was approximately 1:3. These findings endorse a conservative approach to prenatal sonographic monitoring of the kidneys. The RPD reflects the likelihood of obstruction, but there is substantial overlap, and in this ultrasound unit, RPD did not alter the timing of delivery. If RPD is detected early in pregnancy, a single follow-up sonographic study late in pregnancy or after delivery is sufficient.

P02.62: Prenatal diagnosis of giant bladder diverticulum

We report here the unusual case of giant bladder diverticulum diagnosed at 36 weeks' gestation. Ultrasound and MRI prenatal examination show an anechogenous image connected with bladder. Diagnosis of bladder diverticulum was advanced, confirmed by postnatal ultrasound examination and surgical treatment. Congenital bladder diverticulum is a rare malformation, usually diagnosed in the first childhood years when uro-genital complications appear. Pathology underlying this malformation is the same for congenital or acquired bladder diverticulum: it is a bladder mucous membrane protrusion through a detrusor defect. In congenital forms, defect is usually ureteral; still, pathology is well understood only in context of Prune-Belly sequence or Ehler-Danlos syndrome.

Adults with VATER association: Long‐term prognosis

VATER "association" is a common condition, with the diagnosis typically based on a characteristic constellation of congenital anomalies. Reported long-term follow-up information on VATER association is limited, thus making it difficult to prognosticate the future of infants and children with this condition. Further, there are few data on how often the initial diagnosis of VATER association is correct. Some information has been published on growth deficiency and mental retardation, but these data are minimal [Bull et al., 1985; Mapstone et al., 1986; Weaver et al., 1986] and for the most part look at children under the age of 10 years. We have undertaken a long-term follow-up of individuals with VATER association originally reported by Weaver et al. [1986] or diagnosed with VATER association by his associates and him after 1986. Out of the 50 patients, we were able to contact 20 individuals or families. Two of the 20 individuals had died: 1 at 3 days with cardiac failure due to a truncus arteriosus, and 1 at 4 years of unspecified cause. Two were unwilling to participate. Of the rest, we interviewed and examined seven persons, and interviewed another nine by telephone. Of the 16, 5 had some degree of cognitive impairment. These individuals were more likely to have congenital anomalies outside of the typical scope of VATER association, such as prune belly sequence or findings of CHARGE association. Of the nine individuals with a history of imperforate anus, five had partial or complete incontinence as adults leading to difficulties in maintaining employment. Height was at the 5th centile or less in 6 of 16 patients. Three of four patients who were trying to have children, had infertility. In two women, the infertility was thought to be related to congenital anomalies of the genitourinary system and multiple pelvic operations. We also present the long-term medical and neurologic problems in these individuals.

Prune belly syndrome in a patient with only a mildly distended bladder

A 19-year-old G3P1AB1 Caucasian female was referred to us at 14 weeks gestation for oligohydramnios and fetal megacytis. Transabdommal CVS was performed at 15 weeks for rapid chromosomes. Chromosome results were completed two days later, revealing a 46, XY normal male karyotype. A 16-week ultrasound demonstrated anhydramnios, an enlarged fetal bladder and a large amount of fetal ascites. A vesicoamniotic shunt was placed at 16 weeks gestation, and a second shunt was placed at 17 weeks gestation after severe oligohydramnios, megacytis, and fetal ascitis was again noted on ultrasound. A third shunt was placed two days later when the second shunt was presumably not functioning. Follow-up ultrasounds were performed every 3-4 days for the following three weeks, and then monthly to monitor fetal bladder dilation and amniotic fluid volume. Bladder size was consistently mildly enlarged, and amniotic fluid volume was mildly decreased. A lung maturity amniocentesis was performed at 35.8 weeks gestation when oligohydramnios was present. Labor was induced the same day. The patient delivered a male infant with APGAR's of 7 and 9. The infant was transferred to the NICU for close observation. Neither the patient nor the infant exhibited any complications following delivery. The infant boy was subsequently diagnosed with Prune-Belly syndrome, which consists of a triad of anomalies: deficient abdominal wall musculature, urinary tract dilatation, and cryptorchidism. There are two opposing theories regarding the pathogenesis of Prune-Belly syndrome. The first is that the primary defect is a urethral obstruction, causing distention of the bladder, which prevents access of the testes to the inguinal canal, and leads to abdominal distention and subsequent degeneration of the abdominal muscles. The second theory is that the primary defect is in the distribution or quality of the mesoderm, resulting from an insult to the embryonic mesoderm which affects the developing urinary tract, renal and prostatic primordia, and the muscles of the abdominal wall. According to this theory, a urinary tract obstruction could occur as a result of this early defect in the mesoderm. Out case supports the latter theory given the fact that the bladder was only minimally enlarged throughout gestation, and therefore would not appear to explain the clinical presentation of prune belly sequence in our patient.

Congenital anomalies in the teratological collection of Museum Vrolik in Amsterdam, The Netherlands. III: primary field defects, sequences, and other complex anomalies.

The Museum Vrolik collection of the Department of Anatomy and Embryology of the Academic Medical Center, University of Amsterdam, founded by Gerardus Vrolik (1775-1859) and his son Willem Vrolik (1801-1863), consists of more than 5,000 specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, the collection of congenital anomalies, comprising 360 specimens, was recatalogued and redescribed according to contemporary morphogenetic views. The original descriptions, if preserved, were compared with the clinical, radiographical, and magnetic resonance imaging findings. In 120 specimens the following midline anomalies, primary field defects, and sequences were diagnosed: holoprosencephaly sequence; aprosencephaly/atelencephaly; cleft lip; Pierre Robin sequence; omphalocele; diaphragmatic hernia; ectopic heart; bladder exstrophy; cloacal exstrophy; caudal dysgenesis; prune belly sequence; sirenomelia; fetal akinesia sequence; and disruption sequences. Polytopic field defects and associations were diagnosed in 25 specimens. We discuss the opinions of Gerardus and Willem Vrolik, who tried to find reasonable explanations for the dysmorphogenetic entities they investigated, rather than accepting the traditional superstitions.

Acardiac amorphous twin with prune belly sequence in the co‐twin

We describe a twin with acardia acephalus or "Twin Reversed Arterial Perfusion Sequence" and prune belly sequence in the co-twin. In a former quite similar case a prune belly appearance of the co-twin of an acardiac fetus was found to be secondary to the ascites caused by cardiac failure. In the present case, we are dealing with the prune belly sequence as a separate condition, given the fact there were no signs of ascites or cardiac failure. We also found associated anomalies: agenesis of the left ureter and kidney, dysplastic right kidney and anal atresia. Urinary tract obstruction has never been described in the co-twin of an acardiac amorphous fetus.