Material and Method: Six fetuses with prune-belly syndrome were evaluated by postmortem pathological investigation. Characteristic features of the fetuses with this syndrome as well as additional anomalies were evaluated.
Results: Five fetuses were male while one was female. Gestational age ranged from 15 to 22 weeks. A urethral pathology that prevented urinary outflow from the bladder was present in all cases. Marked bladder distension with atrophy of the bladder smooth muscle and abdominal distension with muscular atrophy were also seen in all. Crypto-orchidism, Potter face, pes equinovarus, pulmonary hypoplasia and obstructive renal dysplasia were among the additional noteworthy anomalies.
Conclusion: The pathogenesis of prune-belly syndrome is controversial. More studies are required on the inheritance, etiology and pathogenesis of the prune belly syndrome. Factors affecting the bilaminar and trilaminar germ layer during early 2-3. embryonic week may be considered to explain the pathogenesis of the anomalies seen with this syndrome.
The exact cause of prune belly syndrome is not well known. The possible etiological factors are inheritance, intrauterine infections, mechanical causes, placenta previa, preeclampsia, anemia and parasitic infestations and young maternal age[8,10]. An autosomal recessive or X-linked inheritance is suggested[4,11].
There are two theories regarding the pathogenesis. One is related to obstructive phenomena and states that the accumulation of urine in the bladder causing distention due to the anatomical stenosis of the urethra plays a central role in the development of all signs[2,12]. The second theory blames inadequate mesodermal development between 6 and 10 weeks of gestation stating that this defect simultaneously affects the bladder wall and abdominal wall muscles[2,3,12].
The risk of mortality is high in the intrauterine or early perinatal periods in affected cases. The pulmonary hypoplasia and end stage renal failure said to develop secondary to the lower urinary obstruction are responsible for about 60-75% of deaths[1].
Table I: Characteristic features and concurrent anomalies of six cases with the Prune Belly Syndrome
A urethral pathology that prevented urinary outflow from the bladder, marked bladder distension and abdominal distension were present in all cases (Figure 1, and 2). Cases 2-4 had abnormal histological structures in the proximal urethra showing several microscopic narrow channels and slit-like lumens lined by epithelium (Figure 3). Cases 3 and 5 had no proximal urethra lumen (agenesis). Case 5 showed total obstruction of the proximal urethra lumen and lack of penile erectile tissue development when compared with a normal male fetus of the same gestational week (Figure 4). In contrast to the other cases, Case 6 had a posterior urethral valve and pulmonary hypoplasia. There was no urinary outflow from the bladder due to the presence of lower urinary stenosis in Case 1 but marked postmortem changes and the formalin fixation prevented the dissection that could have provided detailed information. The testes were in the abdomen in all five male fetuses. The pes equinovarus deformity was present in Cases 3, 5 and 6 (Figure 2). There was atrophy of the bladder smooth muscle in all our cases when compared with the bladder of normal fetuses at the same gestational week. Case 3 had striated muscle tissue in the abdominal wall with swelling and necrosis of muscle cells (Figure 5). No striated muscle was found in the abdominal wall of the other cases. There was bilateral ureter dilatation, and bilateral obstructive renal dysplasia characterized by bilateral cystic glomerule and tubule dilatations, decreased number of nephrons, and increased interstitial mesenchymal tissue in Cases 3, 4, 5 and 6 (Figure 6).
Figure 1: Abdominal distension and pes equinovarus deformity of the legs in the 22-week fetus.
Figure 2: Markedly distended bladder in 20-week fetus.
Figure 6: Obstructive renal dysplasia in the kidney of a 20-week fetus (H&E, x40).
The inheritance of the syndrome can be autosomal recessive or X-linked, and 5% of the cases have been shown to develop in monozygotic male twin pregnancies where one fetus is affected and the other is not[4,11]. Our Case 1 had a male twin who developed normally. The presence in males in 95% of the cases, the development of renal failure, the presence of sensory deafness in some cases, and the presence of renal tubular and glomerular pathologies as in 4 of our cases are also seen in Alport syndrome, another X-linked syndrome[18]. The presence of phimosis in the brother of our Case 6 is consistent with X-linked inheritance.
Striated muscle, smooth muscle, and the urethra, kidneys, heart and vessels are of mesodermal origin[6]. While it is possible to explain the pathogenesis of anomalies in organs of mesodermal origin such as the urinary system, abdominal wall striated muscle and the heart, it is difficult to explain the pathogenesis of anomalies in the lung and gastrointestinal system of endodermal origin and the nervous system (sensory deafness) of ectodermal origin that may also accompany the syndrome. More studies are needed on the inheritance, etiology and pathogenesis of the prune belly syndrome. It may be helpful to take into account factors that have a negative effect on the embryo on weeks 2-3 when bilaminar and trilaminar germ layers develop, much earlier than the 6-10th embryonal weeks, to explain the pathogenesis of these anomalies[6].
ACKNOWLEDGEMENT
We would like to thank all the technicians in our laboratory
who followed-up and grouped all the fetuses with anomalies
and supported us on technical issues and especially Ms.
Nurhayat DAL.
1) Bogart MM, Arnold HE, Greer KE: Prune-belly syndrome in
two children and review of the literature. Pediatr Dermatol 2006,
23:342-345 [ Özet ]
2) Woods AG, Brandon DH: Prune-belly syndrome. A focused
physical assessment. Adv Neonatal Care 2007, 7:132-143 [ Özet ]
3) Wigglesworth J.S: Texbook of Fetal and Perinatal Pathology, 2th
ed. Massachusetts, Blackwell Science, 1998, 340, 1008
4) Enid G: Potter's Pathology of the Fetus, Infant and Child, 2th ed.,
Newyork, Mosby-Elsevier, 2007, 354-356
5) Gearhart JP, Lee BR, Partin AW, Epstein JI, Gosling JA: A
quantitative histological evaluation of the dilated ureter of
childhood. II: Ectopia, posterior urethral valfes and the Prune
Belly syndrome. J Urol 1995, 153:172-176 [ Özet ]
6) Sadler T.W: Langman's Medical Embriology, 9th ed., Philadelphia,
Lippincott co, 2004, 206-207, 333-334 339, 51,65
7) Druschel CM: A descriptive study of prune belly in New York
State, 1983 to 1989. Arch Pediatr Adolesc Med 1995, 149:70-76 [ Özet ]
8) Salihu HM, Tchuinguem G, Aliyu MH, Kouam L: Prune belly
syndrome and associated malformations. A 13-year experience
from a developing country. West Indian Med J 2003, 52:281-284 [ Özet ]
9) Levin TL, Soghier L, Blitman NM, Vega-Rich C, Nafday S:
Megacystis-microcolon-intestinal hypoperistalsis and prune
belly: overlapping syndromes. Pediatr Radiol 2004, 34:995-998 [ Özet ]
10) Peshev ZV, Krusteva MB, Danev VH: A case of prune belly
syndrome. Folia Med (Plovdiv) 2000, 42:66-88 [ Özet ]
11) Nouaili EB, Chaouachi S, Nouira F, Benmassoud I, Laabidi
K, Chaouachi B, Marrakchi Z: Concordant posterior urethral
valves in male monochorionic twins with secondary prune belly
syndrome. Tunis Med 2008, 86:1086-1088 [ Özet ]
12) Volmar KE, Nguyen TC, Holcroft CJ, Blakemore KJ, Hutchins
GM: Phimosis as a cause of the prune belly syndrome: comparison
to a more common pattern of proximal penile urethra obstruction.
Virchows Arch 2003, 442:169-172 [ Özet ]
13) Kumar V, Abbas A, Fausto N: Robbins and Cotran Pathologic
Basis of Disease, 7th ed., Philadelphia, Saunders- Elsevier, 2005,
1013
14) Volmar KE, Fritsch MK, Perlman EJ, Hutchins GM: Patterns of
congenital lower urinary tract obstructive uropathy: relation to
abnormal prostate and bladder development and the prune belly
syndrome. Pediatr Dev Pathol 2001, 4:467-472 [ Özet ]
15) Alhawsawi AM, Aljiffry M, Walsh MJ, Peltekian K, Molinari M:
Hepatic artery aneurysm associated with prune belly syndrome:
a case report and review of the literature. J Surg Educ 2009, 66:43-
47 [ Özet ]
16) Al Harbi NN: Prune-belly anomalies in a girl with Down
syndrome. Pediatr Nephrol 2003, 18:1191-1192 [ Özet ]
17) Sinico M, Touboul C, Haddad B, Encha-Razavi F, Paniel JB,
Gicquel C, Gérard-Blanluet M: Giant omphalocele and “prunebelly”
sequence as components of the Beckwith-Wiedemann
syndrome. Am J Med Genet A 2004, 129A:198-200 [ Özet ]