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Clinical Case Reports Jul 2024Polymelia (supernumerary limbs) is an extremely rare congenital condition in humans. Because congenital anorectal malformation is a relatively common complication of...
Polymelia (supernumerary limbs) is an extremely rare congenital condition in humans. Because congenital anorectal malformation is a relatively common complication of polymelia and it may require emergency surgery as in the present case, accompanying malformations must be investigated.
PubMed: 38919885
DOI: 10.1002/ccr3.9119 -
Italian Journal of Pediatrics Jun 2024Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous...
BACKGROUND
Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the "hotspot region", which is particularly susceptible to mutation.
METHODS
In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations.
RESULTS
We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein.
CONCLUSIONS
Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment.
Topics: Humans; Transcription Factors; Abnormalities, Multiple; Anus, Imperforate; Female; Male; Pedigree; China; Mutation; Rare Diseases; Anorectal Malformations; Asian People; East Asian People; Hearing Loss, Sensorineural; Thumb
PubMed: 38915054
DOI: 10.1186/s13052-024-01691-0 -
Urology Jun 2024Congenital true diphallia, complete duplicate bladder, bladder exstrophy and anorectal malformation in a child are uncommon. Here, we present the case of a...
Congenital true diphallia, complete duplicate bladder, bladder exstrophy and anorectal malformation in a child are uncommon. Here, we present the case of a three-year-old boy with multiple genitourinary malformation, including true diphallia, complete duplicate bladder, bladder exstrophy, epispadias, and anorectal malformation. Multi-departmental collaborative treatment for complex conditions ultimately achieved an ideal appearance for this patient. All vital signs were stable after the surgery and they remained consistent during follow-up. In such cases, surgical correction is individualized to achieve adequate urinary continence and erection with adequate esthetics.
PubMed: 38914230
DOI: 10.1016/j.urology.2024.06.031 -
Journal of Indian Association of... 2024To study the safety and feasibility of enhanced recovery after surgery (ERAS) protocol in pediatric colostomy closure.
AIMS
To study the safety and feasibility of enhanced recovery after surgery (ERAS) protocol in pediatric colostomy closure.
MATERIALS AND METHODS
Retrospective observational study of children who underwent colostomy closure. Data were collected from the electronic medical records and telephonic follow-up calls of patients from October 2013 to October 2023, in the Department of Pediatric Surgery of a Tertiary level Medical College. The parameters obtained were age, gender, type of stoma, primary diagnosis, discrepancy in luminal diameters, time to reach full feeds, postoperative hospital stay, and complications. The protocol followed for colostomy closure included the following-no bowel preparation or nasogastric tube, no overnight fasting, single dose of antibiotic prophylaxis, avoiding opioids, packing proximal stoma till mobilization and starting early oral feeds postoperatively. The continuous parameters were expressed as mean ± standard deviation or median (range) while the descriptive parameters were expressed as number and percentage.
RESULTS
A total of 90 patients were included in the study. Most of the patients had colostomy for anorectal malformation. Five of them had significant luminal discrepancy of 4 or more times. Full feeds were reached within 2 days in 79 patients. Postoperative hospital stay was 2-3 days in 62 patients. Six patients stayed for more than 5 days, due to complications requiring further management. We noted surgical site infection in 6 patients all of whom were managed with regular wound dressings and fecal fistula in 4 cases, two of which resolved spontaneously.
CONCLUSION
ERAS protocol in colostomy closure reduces the hospital stay and is cost effective, with early recovery and no added complications.
PubMed: 38912032
DOI: 10.4103/jiaps.jiaps_245_23 -
Urology Jun 2024Caudal duplication syndrome is a rare congenital anomaly with various duplications of structures derived from the embryonic cloaca and notochord. A male neonate was born...
Caudal duplication syndrome is a rare congenital anomaly with various duplications of structures derived from the embryonic cloaca and notochord. A male neonate was born with diphallia, bifid scrotum and duplicated anorectal malformation. Diagnostic and operative evaluation identified a partially duplicated right kidney with left-to-right crossed fused ectopia, bilateral hydronephrosis, two separate hemi-bladders, left ectopic ureter with vesicoureteral reflux, and a left rectourethral fistula. To our knowledge, this is the first reported caudal duplication anomaly with complete genitourinary duplication, with diphallia, duplicated bladder, bifid scrotum, extra-numerary kidneys and a duplicated rectum.
PubMed: 38908563
DOI: 10.1016/j.urology.2024.06.028 -
Kidney International Reports Jun 2024Townes-Brocks syndrome (TBS), a rare autosomal dominant genetic condition associated with (Spalt like Transcription Factor 1), is reported to be present in 1:238,000...
INTRODUCTION
Townes-Brocks syndrome (TBS), a rare autosomal dominant genetic condition associated with (Spalt like Transcription Factor 1), is reported to be present in 1:238,000 individuals in the general population. TBS is characterized by the triad of anorectal malformations, dysplastic ears, with or without hearing impairment, and hand or thumb anomalies. Although kidney involvement is less common in TBS, the disease can progress to kidney failure. Here, we sought to characterize the incidence of variants in individuals undergoing broad-based genetic testing with a kidney gene panel and to quantify the presence of (extra)renal features.
METHODS
A retrospective analysis of the genetic data from a 385-gene panel identified cases with a pathogenic (P) or likely pathogenic (LP) variant in . Data including age, features, and disease progression were collected.
RESULTS
Of 35,044 samples, P or LP variants in were identified in 22, yielding a prevalence of 1:1592 among patients tested for monogenic kidney disease, and 1:342 among cases identified with a monogenic kidney disease. Among this cohort, the median patient age was 23 years (range: 3 months-62 years) with chronic kidney disease (CKD) reported in 91% (20/22) of cases. Reported kidney features included renal agenesis/hypoplasia (7/22; 32%), focal segmental glomerulosclerosis (4/22; 18%), and kidney cysts (3/22; 14%). Confirmed extrarenal features included hearing loss and/or ear features (7/22; 32%), anorectal malformations (6/22; 27%) and hand or thumb abnormalities (4/22; 18%). Three patients (3/22; 14%) had both TBS diagnoses and the traditional "triad."
CONCLUSION
Traditionally, a molecular diagnosis was ascertained primarily in individuals presenting with cardinal features of TBS; therefore, individuals with mild or atypical presentations were often overlooked clinically. Our findings reveal that P/LP variants could be a consequential contributor to monogenic kidney disease.
PubMed: 38899216
DOI: 10.1016/j.ekir.2024.03.030 -
Journal of Pediatric Surgery May 2024Fecal incontinence is a common problem for children with repaired anorectal malformations (ARM) and has significant implications for initiating school. While sex,...
BACKGROUND
Fecal incontinence is a common problem for children with repaired anorectal malformations (ARM) and has significant implications for initiating school. While sex, anatomy, and medical comorbidities are known to influence continence outcomes, the impact of socioeconomic factors and neighborhood-level disadvantage are less well understood.
METHODS
We performed a single-center retrospective review of all school-aged (5-18 years) children with ARM at a longitudinal pediatric surgery clinic. Demographic, clinical, and socioeconomic variables were abstracted via chart review and geocoding was performed to obtain Area Deprivation Index (ADI) and Social Vulnerability Index (SVI) scores. Statistical analyses assessed for associations between the primary outcome of social continence (defined as no diaper usage and infrequent fecal accidents at age 5) and these variables.
RESULTS
72 patients were included; of these, 45.8% were socially continent. On bivariate analysis, social continence was significantly associated with state ADI score as well as the SVI Housing characteristics score. These associations remained significant when adjusting for sex and medical comorbidities in separate multiple logistic regression models.
CONCLUSION
The relative disadvantage of the neighborhood in which a child with ARM lives may play a role in their ability to achieve continence by school age. Efforts are warranted to identify and develop targeted interventions to for this pediatric population.
LEVEL OF EVIDENCE
IV.
PubMed: 38897896
DOI: 10.1016/j.jpedsurg.2024.05.013 -
Archives of Disease in Childhood. Fetal... Jun 2024The optimal time for neonatal stoma closure is unclear and there have been calls for a trial to compare early and late surgery. The feasibility of such a trial will...
OBJECTIVE
The optimal time for neonatal stoma closure is unclear and there have been calls for a trial to compare early and late surgery. The feasibility of such a trial will depend on the population of eligible infants and acceptability to families and health professionals. In this study, we aimed to determine current UK practice and characteristics of those undergoing stoma surgery.
DESIGN
A retrospective cohort study of neonates who had undergone stoma surgery (excluding anorectal malformations and Hirschsprung's disease) using three national databases: the National Neonatal Research Database (NNRD, 2012-2019), British Association of Paediatric Surgeons Congenital Anomalies Surveillance System (BAPS-CASS, 2013-2014) and Hospital Episode Statistics-Admitted Patient Care (HES-APC, 2011-2018).
RESULTS
1830 eligible neonates were identified from NNRD, 163 from BAPS-CASS, 2477 from HES-APC. Median (IQR) duration of stoma in days was 57 (36-80) in NNRD, 63 (41-130) in BAPS-CASS and 78 (55-122) for neonates identified from HES-APC. At the time of closure, there were low rates of invasive ventilation (13%), inotrope use (5%) and recent steroids use (4%). Infants who underwent earlier closure (<9 weeks) were less preterm (median 28 weeks vs 25 weeks), have higher birth weight (median 986 g vs 764 g) and more likely to have stoma complications (29% vs 5%).
CONCLUSION
There are sufficient UK neonates undergoing stoma formation for a trial. Stoma closure is performed at around 2 months, with clinical stability, gestation, weight and stoma complications appearing to influence timing. The variation in practice we document indicates there is opportunity to optimise practice through a trial.
PubMed: 38897635
DOI: 10.1136/archdischild-2024-327020 -
Cureus May 2024Introduction Congenital malformation studies serve several purposes, including establishing baseline rates, monitoring changes over time, exploring the origins of these...
Introduction Congenital malformation studies serve several purposes, including establishing baseline rates, monitoring changes over time, exploring the origins of these defects, and helping in planning health services. Increasing public awareness about pediatric surgical interventions is another goal of these studies. However, the impact of congenital malformations is often underestimated in developing countries due to insufficient healthcare data and diagnostic facilities, particularly in rural areas. Families affected by the birth of a child with congenital malformations face significant stress and hardship. Methods The main aims of this study were to evaluate the clinical pattern of congenital structural malformations in our region (Uttarakhand, India), identify possibly associated factors of congenital malformations, and find out the immediate outcome of congenital malformations in enrolled participants. Results Among a total of 150 cases, 73 (48.7%) cases were inborn, whereas 77 (51.3%) cases were outborn. Investigation of congenital malformation revealed cleft lip or palate in 37 (24.7%) cases, congenital heart disease (CHD) in 33 (22%) cases, meningomyelocele (MMC) in 18 (12.0%) cases, anorectal malformation (ARM) in 11 (7.3%) cases, hypospadias in 10 (6.7%) cases, congenital talipes equinovarus (CTEV) in nine (6.0%) cases, tracheoesophageal fistula (TEF) in nine (6.0%) cases, polydactyly in seven (4.7%) cases, pelviureteric junction obstruction (PUJO) in four (2.7%) cases, duodenal atresia in three (2.0%) cases, midgut volvulus in three (2.0%) cases, umbilical sinus in two (1.3%) cases, sacrococcygeal teratoma (SCT) in one (0.7%) case, phimosis in one (0.7%) case, microtia in one (0.7%) case, and micrognathia in one (0.7%) case. Mortality was observed in 11 (7.3%) cases, whereas 105 (70%) cases were successfully discharged. Among 11 mortality cases, the cause of death was CHD in seven (63.2%) cases, TEF+CHD in two (18.1%) cases, MMC in one (9%) case, and duodenal atresia in one (9%) case. Conclusion Contrary to the common belief that advanced maternal age of greater than 35 years is a major cause, 86.6% of the congenital structural anomalies in our hospital-based study in Uttarakhand occurred in babies of mothers belonging to the age group of 18-30 years. Also, consanguineous marriage was observed in only 3.3% of cases, indicating that it may not be a major contributing factor causing congenital structural malformations in our region. External congenital anomalies are most commonly observed (60.7%), with cleft lip and cleft palate being the most common. The most frequently observed internal congenital anomaly is CHD (22%) followed by gastrointestinal (GI) (18.6%) and urinary anomalies (10.1%). Death and referral are commonly seen in CHD.
PubMed: 38883135
DOI: 10.7759/cureus.60375 -
Developmental Biology Jun 2024Anorectal malformation (ARM) is the most common congenital digestive tract anomaly in newborns, and children with ARM often have varying degrees of underdevelopment of...
Anorectal malformation (ARM) is the most common congenital digestive tract anomaly in newborns, and children with ARM often have varying degrees of underdevelopment of the pelvic floor muscles (PFMs). To explore the effects of RARα and Pitx2 on the development of rat PFMs, we constructed a rat ARM animal model using all-trans retinoic acid (ATRA), and verified the expression of RARα and Pitx2 in the PFMs of fetal rats. Additionally, we used rat myoblasts (L6 cells) to investigate the regulatory roles of RARα and Pitx2 in skeletal muscle myoblast differentiation and their interactions. The results indicated a significant decrease in the expression of RARα and Pitx2 in the PFMs of fetal rats with ARM. ATRA can also decrease the expression of RARα and Pitx2 in the L6 cells, while affecting the differentiation and fusion of L6 cells. Knocking down RARα in L6 cells reduced the expression of Pitx2, MYOD1, MYMK, and decreased myogenic activity in L6 cells. When RARα is activated, the decreased expression of Pitx2, MYOD1, and MYMK and myogenic differentiation can be restored to different extents. At the same time, increasing or inhibiting the expression of Pitx2 can counteract the effects of knocking down RARα and activating RARα respectively. These results indicate that Pitx2 may be downstream of the transcription factor RARα, mediating the effects of ATRA on the development of fetal rat PFMs.
PubMed: 38878992
DOI: 10.1016/j.ydbio.2024.06.006