Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene.

BACKGROUND: Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases. METHODS: We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations. RESULTS: We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19-21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor ß-integrin 1 (ITGß1). CONCLUSIONS: FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.

PATTERN AND OUTCOME OF RENAL DISEASES IN HOSPITALIZED CHILDREN IN TIKUR ANBESSA SPECIALIZED TEACHING HOSPITAL, ADDIS ABABA, ETHIOPIA.

Background: Renal diseases are major causes of morbidity and mortality in pediatric practice. Pediatric patients with renal disease, especially younger ones may present with nonspecific signs and symptoms unrelated to the urinary tract. Unexplained fever or failure to thrive may be the only manifestation. Most children with renal diseases in our hospital arrive very late either because of inadequate health awareness among the parents or failure of recognizing the symptoms of renal diseases at a lower health care level. This review will highlight the symptoms of renal diseases at presentation and outcomes of treatment in children in a major referral hospital. Methods: A cross-sectional retrospective chart review was done over a period of 3 years (June, 2012 to May, 2015) in 381 admitted children (Birth-17 years) at Tikur Anbessa Specialized Teaching Hospital in Addis Ababa, Ethiopia. Results: Out of 14521 pediatric ward admissions in the study period, kidney diseases accounted for 473 admissions in 381 children, accounting for 3.3% of all admissions. The three most common renal diseases observed were congenital anomalies of the kidney and urinary tract (CAKUT) seen in 127 children (26.8%), followed by nephrotic syndrome in 80 children 16.9% and acute glomerulonephritis in 58 children (12.2%). Other renal diseases observed were urinary tract infection 8.0%, urolithiasis 6.7%, Wilm's tumor 6.3%, acute kidney injury 4.2% and chronic kidney disease 4.0%. Other less frequently detected diseases were bladder exstrophy, lupus nephritis, Henock shonlein Purpura nephritis and prune-belly syndrome. Out of 381 children 207 (54.3%) recovered normal renal function, 20(5.2%) remained with proteinuria, 13(3.4%) progressed to chronic kidney disease and 11(2.9%) died. Sixty one nephrotic children (76.3%) achieved remission but 17 children (21.3%) remained with proteinuria; one steroid resistant child died of end stage renal disease. Ten children (2.6%) with different renal diseases were lost to follow-up and 5 (1.3%) discharged against medical advice. Conclusions: This data reflects that many of the renal diseases are preventable or potentially curable. Therefore, improvement of pediatric renal services and training of health workers would help in early detection and treatment of these conditions leading to reduction in their morbidity and mortality.

Prune-Belly syndrome, a rare case presentation in neonatology: about one case in Yaounde, Cameroon.

The Prune-Belly syndrome (PBS) is a rare pathology predominating in male infants, classically manifesting with the triad including aplasia of the abdominal wall muscles, dilatation of the urinary tract, and testicular abnormalities. We report and discuss the case of a full-term male newborn, in whom clinical examination at birth revealed abdominal wall muscle hypoplasia, cryptorchidism, urinary tract dilatation and renal failure. The diagnosis was made based on physical assessment, abdominal ultra-sonographic imaging, and blood sampling of urea and creatinine. For such cases, the recommended surgical management usually consists in a sequential surgical intervention including urinary tract reconstruction, abdominoplasty, and orchidopexy. However, these could not be practiced in due time in our patient, who died on the seventh day of life because of kidney failure. The prognosis of infants with Prune-Belly syndrome may be improved by quality antenatal follow-up, to enable the early diagnosis and preparation for prompt surgical intervention.

Gonadal Function and Reproductive System Anatomy in Postpubertal Prune-Belly Syndrome Patients.

OBJECTIVE: To gain insight into the causes of infertility in Prune Belly Syndrome (PBS) by evaluating reproductive system anatomy and gonadal function in a cohort of postpubertal PBS patients. METHODS: We contacted all PBS patients 14 years old or older treated and followed at our institution. Age at orchiopexy, type of orchiopexy (with or without ligation of gonadal vessels), testicular volumes and positions were evaluated. Pelvic magnetic resonance imaging (to assess prostate size, seminal vesicles, and vas) and hormonal profile were ordered. Sperm analysis and analysis of urine after masturbation were performed after informed consent. RESULTS: Fifteen patients were included in this study. Mean age was 19.2 years. Mean age at orchiopexy was 18 months. Fourteen patients (93.3%) had normal and orthotopic testes. Mean testicular volume was 6.9 cc. Eight patients collected semen, 5 of them (62.5%) had spermatozoa in the specimen and motile sperm was found in 4 (50%). Mean hormone levels were LH: 5.3 mg/dL, FSH: 6.9 mg/dL, testosterone 531 mg/dL. Magnetic resonance imaging revealed hypoplastic prostates in 66.6% and unilateral seminal vesicle absence in 66.6%. No vasal abnormality was noted. CONCLUSION: Patients with PBS may have normal sexual hormonal levels. Motile spermatozoa were found in half of the patients. Our study highlights a high prevalence of prostate and seminal vesicle abnormalities that may represent an important cause for their infertility.

Differences in Linea Alba Stiffness and Linea Alba Distortion Between Women With and Without Diastasis Recti Abdominis: The Impact of Measurement Site and Task.

BACKGROUND: The biomechanical implications of diastasis recti abdominis (DRA) are unknown. OBJECTIVES: To (1) investigate the impact of DRA, measurement site, and task on inter-rectus distance (IRD), linea alba (LA) stiffness, and LA distortion measured at rest and during head-lift and semi-curl-up tasks; and (2) describe the relationships among IRD, LA stiffness, and LA distortion. METHODS: In this cross-sectional, observational cohort study, brightness-mode ultrasound imaging and shearwave elastography were used on a sample of 20 women. Inter-rectus distance, LA stiffness, and LA distortion were measured at 3 locations, while at rest and during head-lift and semi-curl-up maneuvers. All outcomes were compared between groups (DRA versus no DRA), sites, and tasks. Linear regression models were used to evaluate the relationships among IRD, mean and peak LA stiffness, and LA distortion. RESULTS: Eleven women with and 9 without DRA participated. Women with DRA demonstrated lower peak and mean LA stiffness and higher LA distortion compared to women without DRA. In women with DRA, IRD and LA distortion were not influenced by measurement site; IRD decreased, LA distortion increased, and LA stiffness did not change during the head lift and semi-curl-up compared to rest. In women without DRA, the LA was least stiff closest to the umbilicus; it increased in stiffness during the head lift and semi-curl-up and did not distort or change compared to rest. CONCLUSION: Diastasis recti abdominis was associated with low LA stiffness and with LA distortion during a semi-curl-up task; the amount of distortion was a function of IRD and LA stiffness. J Orthop Sports Phys Ther 2019;49(9):656-665. Epub 26 Mar 2019. doi:10.2519/jospt.2019.8543.

Diastasis of rectus abdominis muscles in low back pain patients.

BACKGROUND: Abdominal muscles are important spinal stabilizers and its poor coordination, as seen in diastasis of rectus abdominis (DRA), may contribute to chronic low back pain (LBP). However, this has not yet been studied directly. OBJECTIVES: To conduct a pilot study to examine the association between DRA and LBP. METHODS: Using a digital caliper, standard clinical DRA measurement was performed in 55 participants with and 54 without chronic LBP. RESULTS: Participants were on average 55 years old, 69 (63%) were women. Among the 16 participants with DRA, 11 (69%) had chronic LBP; among the 93 participants without DRA, 44 (47%) had LBP. Among men, 7 of 9 (77%) with DRA had LBP and 14 of 31 (45%) without DRA had LBP. Among women, 4 of 7 (57%) with DRA had LBP and 30 of 62 (48%) without DRA had LBP. BMI was the strongest correlate of DRA and may explain the relation between DRA and chronic LBP. CONCLUSIONS: DRA and LBP may be interrelated, especially among men. This may be a function of greater BMI in individuals with chronic LBP. Understanding the association between DRA, LBP, and BMI may have important implications for treatment of LBP and for intervention.

Three cases of prune belly syndrome at the Lagos State University Teaching Hospital, Ikeja.

Prune belly syndrome (PBS) is a rare congenital disorder affecting 2.5 to 3.8/100,000 live births worldwide. Our objective of this report is to describe clinical manifestation, laboratory, and radiological characteristics of PBS in our patients, to highlight the limitations to offering appropriate patient care due to parents demanding discharge against medical advice and the need to increase the awareness regarding this rare disease. We report three cases; all referred after birth with lax abdominal wall, congenital anomalies of kidney, and urinary tract. One of the patients had an absent right foot. They all had cryptorchidism, and in one, there was deranged renal function. The reported cases had both medical and radiological interventions to varying degrees. They all had an abdominal ultrasound which revealed varying degrees of hydronephrosis, hydroureters, and bladder changes. Voiding cystourethrogram showed vesicoureteric reflux in one of the reported cases. Urinary tract infections were appropriately treated with antibiotics based on sensitivity. PBS management in our setting remains a challenge because of strong cultural beliefs, and high rate of discharge against medical advice. Focus should be on parent education, early diagnosis, and multidisciplinary management approach.

The importance of an intact abdominal musculature mechanism in maintaining spinal sagittal balance. Case illustration in prune-belly syndrome.

STUDY DESIGN: A rare case of thoracic hypokyphotic deformity secondary to prune-belly syndrome is presented. OBJECTIVES: To discuss the role of an intact abdominal musculature mechanism in maintaining spinal sagittal balance, and to present a case illustration of prune-belly syndrome. SUMMARY OF BACKGROUND DATA: There has been an ongoing debate concerning the integrity of the abdominal musculature unit in maintaining spinal support and stability. It is now believed that intra-abdominal pressure hitherto generated plays an important role in the stabilization of the spine. Congenital aplasia of the abdominal musculature, termed prune-belly syndrome, might therefore result in the loss of spinal function and stability. The literature also is reviewed for the incidence of spinal deformities related to this condition. METHODS: A unique case of prune-belly syndrome in a 33-year-old man with congenital aplasia of the abdominal musculature is presented. RESULTS: The patient exhibited loss of the spinal sagittal balance, with resultant development of a thoracic hypokyphotic deformity and thoracolumbar scoliosis. CONCLUSIONS: Scoliosis appears to be the most commonly reported spinal deformity. Unequal compressive forces on the vertebral endplates may be the proposed mechanism for the spinal deformities. Compensatory lumbar paraspinal overactivity resulting from the inability to generate normal intra-abdominal pressures because of a deficient abdominal wall musculature mechanism seems to be the plausible explanation for the observed thoracic hypokyphatic deformity.

Peritoneal dialysis in the prune belly syndrome.

OBJECTIVES: To describe our experience with chronic ambulatory peritoneal dialysis in children with the prune belly syndrome (PBS). DESIGN: From our peritoneal dialysis (PD) program we were able to review the medical records of 6 boys with PBS. Data were collected on potential complications such as infections, hernias, growth, and problems encountered with PD catheter insertion. RESULTS: The ages of the 6 boys ranged from 10 months-17 years. The dialysis duration was from 9-22 months, with a total of 76 patient-months on PD. There was one death, possibly as a complication of an exit-site infection. Five received a renal transplant, and 4 have functioning grafts. Peritonitis occurred once in every 10.8 patient-months, and exit-site or tunnel infection was diagnosed every 7.6 patient-months. Four patients required PD catheter replacement because of tunnel infection in 2, persistent exit-site infection in 1, and fluid leakage in 1. Of a total of nine catheters, three were inserted using a laparoscopic technique. There were no leaks in these three; however, there was one exit-site infection. Two patients had inguinal hernias that required surgery. CONCLUSION: Deficiency of abdominal musculature in PBS poses potential problems for the use of PD, in particular, catheter anchorage, exit-site healing, and leakage. In our patients the most serious complications were infections of the exit site or catheter tunnel. Our experience suggests that a laparoscopic technique may provide improved catheter placement. PD offers a potentially successful form of dialysis for patients with PBS.

Limited surgical intervention in the prune belly syndrome.

Experience with 16 males with prune belly syndrome reveals that half have done well without any surgical treatment. The authors felt that two patients had unnecessary loop cutaneous ureterostomies--and inappropriate operation for these children. Urethral obstruction was found in two boys. Four neonates died of severe renal dysplasia. Although the distal ureters are dilated, they adequately conduct urine and seldom need shortening, tailoring, and reimplantation.

Megalourethra associated with prune-belly syndrome.

A 14-day-old male infant with megalourethra is presented because of the rarity of the anomaly and its association with prune-belly syndrome. The lax, wrinkled appearance of the abdomen, bilateral cryptorchidism and severe dilatation of the urinary system are features included in the classic triad of the prune-belly syndrome. Our patient had the scaphoid variety of megalourethra since the penis appeared elongated and floppy in the fusiform form.

Surgical treatment with the technique of Galveston-Luque of spine deformities associated with the prune belly syndrome.

In prune belly syndrome (PBS), spine deformities, particularly scoliosis, are the most frequent accompanying orthopedic problem (18%). We give a detailed description of two cases with prune belly-associated spine deformities. A combined anterior-posterior fusion procedure with posterior correction and stabilization according to the Galveston-Luque technique was carried out in both patients. In one patient insufficiency of the pelvic fixation developed with loss of balance. Reoperation was performed. In the second patient correct alignment and balance was achieved, breakage of both metal rods occurred over time. The PBS represents a model of how scoliosis may emerge. The lack of the abdominal musculature subsequently leads to congenial imbalance, which may cause lordo-scoliotic deformity. The operative treatment of spine deformities in the PBS in the presented technique is efficient. In great deformities balance is difficult to achieve and maintain especially in the lumbo-sacral junction.

Pathophysiologic and anesthetic correlations of the prune-belly syndrome.

"Prune-Belly" is the name given to the disease which is characterized by a congenital wrinkled appearance of the abdomen. Usually, a triad of congenital anomalies highlights the components of the prune-belly syndrome. This triad consists of undescended testicles, abdominal musculature deficiency and urinary tract abnormalities. The previously described triad of the syndrome is by no means the total spectrum of the disease. Prune-belly syndrome is also associated with diseases of the respiratory, cardiovascular, skeletal, gastrointestinal and central nervous systems. Associated diseases of major body systems which are caused by renal and cardiopulmonary anomalies, as well as the surgical procedure to be performed, influence the plan for the administration of anesthesia. The nature of the genitourinary diseases in the prune-belly baby may obviate the need for surgical intervention as early as the neonatal period of life. Although this congenital disease occurs with some rarity, the gravity of the syndrome demands an in-depth knowledge of its pathophysiology in order to assure uncomplicated anesthetic care. Astute surveillance during preanesthetic, anesthetic, and postanesthetic management is germane to the prevention of mishaps.

[Prune belly syndrome]. / La sindrome di "prune belly".

The prune belly syndrome consists of congenital absence or deficiency of the anterior abdominal muscle, bilateral cryptorchidism and anomalies of urogenital tract. Neurological problems are common in these patients as respiratory, orthopedic, gastrointestinal and chromosomal anomalies. We have treated 17 cases of prune belly syndrome. Mortality is 23.5%: two patients died in the neonatal period of respiratory failure; one patient, aged two months, died of septicemia in postoperative period, another, 14 years old, died of respiratory failure with normal renal function. Two patients are female without urological anomalies, one male has an incomplete form with normal urinary tract. Two patients with complete syndrome are treated conservatively. Ten patients with vesicourethral reflux or ureteral dilatation for distal obstruction are treated surgically. We performed 20 ureteral reimplantations with 16 tailoring of the ureters. In three patients ureteral reimplantation failed and in these patients we performed successfully a transureteroureterostomy. All patients have adequate complete bladder emptying without surgical procedure. Renal function is normal in seven, slightly reduced in one and reduced but stable in the others. Orchidopexy was performed successfully in eleven patients (10 Fowler-Stephens procedures). Orchiectomy with testicular prosthesis was performed in a patient 12 years old. Five patients have moderate respiratory insufficiency treated with chest physiotherapy. Urinary tract abnormalities are the most common cause of morbidity and mortality in patients with prune belly syndrome. Treatment regimen must be individualized. Respiratory problems are also frequent and is mandatory a precocious chest physiotherapy.

Prune belly syndrome. A focused physical assessment.

Prune belly syndrome, a rare congenital anomaly, exists almost exclusively in males and consists of genital and urinary abnormalities with partial or complete absence of abdominal wall musculature. The syndrome, caused by urethral obstruction early in development, is the result of massive bladder distention and urinary ascites, leading to degeneration of the abdominal wall musculature and failure of testicular descent. The impaired elimination of urine from the bladder leads to oligohydramnios, pulmonary hypoplasia, and Potter's facies. The syndrome has a broad spectrum of affected anatomy with different levels of severity. The exact etiology of prune belly syndrome is unknown, although several embryologic theories attempt to explain the anomaly. With advances in prenatal screening techniques, the diagnosis and possible treatment of prune belly syndrome can occur before birth, although controversy exists on the proper management of prune belly syndrome. This article explores the theories behind the pathophysiology and embryology of prune belly syndrome and its multisystemic effects on the newborn infant. Specific attention is paid to presentation, clinical features, head-to-toe physical assessment, family support, and nursing care of infants with prune belly syndrome.

Respiratory function in the prune-belly syndrome.

Respiratory function was evaluated in 11 patients with prune-belly syndrome. Nine had evidence of gas trapping and six of restrictive lung disease. These abnormalities of lung function appear to be secondary to the musculoskeletal disorder associated with prune-belly syndrome rather than parenchymal lung disease.