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European Journal of Medical Genetics May 2024Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly...
Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for ARID1A-related CSS.
PubMed: 38735569
DOI: 10.1016/j.ejmg.2024.104948 -
Journal of Medical Case Reports May 2024Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized...
BACKGROUND
Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized by partial or complete fusion of lower extremities, renal agenesis, absent urinary tract, ambiguous external genitalia, imperforate anus, and single umbilical artery. Sirenomelia is often associated with several visceral congenital malformations, rendering it invariably incompatible with extrauterine life.
CASE PRESENTATION
We present the case of 22-year-old Black African woman who delivered a term newborn by caesarean section at a gestation age of 37 weeks due to obstructed labor with fetal distress. The newborn was a fresh stillbirth weighing 2100 g and had fusion of the lower extremities, a single upper limb, ambiguous genitalia, imperforate anus, and a cleft lip. The mother had made only two prenatal visits, at which she was found to be normotensive and normoglycemic. She was not screened for routine fetomaternal infections and missed supplementation for folic acid during the critical first trimester. She did not undergo any obstetric ultrasonography. The parents of the newborn were not close relatives and there was no family history of consanguinity. Further genetic testing was not performed due to lack of laboratory capacity, and post mortem examination was not permitted due to cultural taboo and restrictions relating to handling of deceased newborns.
CONCLUSION
Sirenomelia is a rare congenital malformation with very poor prognosis. Specific interventions during pre-conception and early prenatal care are critical in the prevention of specific congenital anomalies. Early obstetric ultrasonography is invaluable for diagnosis of sirenomelia as well as counseling for possible termination of pregnancy.
Topics: Humans; Female; Infant, Newborn; Ectromelia; Cleft Lip; Pregnancy; Abnormalities, Multiple; Young Adult; Stillbirth; Tanzania
PubMed: 38706003
DOI: 10.1186/s13256-024-04549-5 -
Children (Basel, Switzerland) Apr 2024Neonates with a new diagnosis of anorectal malformation (ARM) present a unique challenge to the clinical team. ARM is strongly associated with additional midline...
Neonates with a new diagnosis of anorectal malformation (ARM) present a unique challenge to the clinical team. ARM is strongly associated with additional midline malformations, such as those observed in the VACTERL sequence, including vertebral, cardiac, and renal malformations. Timely assessment is necessary to identify anomalies requiring intervention and to prevent undue stress and delayed treatment. We utilized a multidisciplinary team to develop an algorithm guiding the midline workup of patients newly diagnosed with ARM. Patients were included if born in or transferred to our neonatal intensive care unit (NICU), or if seen in clinic within one month of life. Complete imaging was defined as an echocardiogram, renal ultrasound, and spinal magnetic resonance imaging or ultrasound within the first month of life. We compared three periods: prior to implementation (2010-2014), adoption period (2015), and delayed implementation (2022); ≤ 0.05 was considered significant. Rates of complete imaging significantly improved from pre-implementation to delayed implementation (65.2% vs. 50.0% vs. 97.0%, = 0.0003); the most growth was observed in spinal imaging (71.0% vs. 90.0% vs. 100.0%, = 0.001). While there were no differences in the rates of identified anomalies, there were fewer missed diagnoses with the algorithm (10.0% vs. 47.6%, = 0.05). We demonstrate that the implementation of a standardized algorithm can significantly increase appropriate screening for anomalies associated with a new diagnosis of ARM and can decrease delayed diagnosis. Further qualitative studies will help to refine and optimize the algorithm moving forward.
PubMed: 38671711
DOI: 10.3390/children11040494 -
International Journal of Surgery Case... May 2024OEIS complex is a rare and complex anomaly of the genitourinary and intestinal tract. It includes Omphalocele, Exstrophy of cloaca, Imperforate anus and Spinal defects.
INTRODUCTION AND IMPORTANCE
OEIS complex is a rare and complex anomaly of the genitourinary and intestinal tract. It includes Omphalocele, Exstrophy of cloaca, Imperforate anus and Spinal defects.
PRESENTATION OF CASE
We are reporting a case of OEIS complex.
CLINICAL DISCUSSION
Cloacal exstrophy is considered the most severe ventral abdominal wall defect. Diagnosis is primarily antenatal based on the presenting features on ultrasonography. Management requires initial resuscitation and stabilization followed by either single staged closure or multistage procedures by multi-disciplinary surgical team.
CONCLUSION
The introduction of better diagnostic techniques and the detection of fetal malformations during pregnancy is it's the cornerstone of care.
PubMed: 38643654
DOI: 10.1016/j.ijscr.2024.109640 -
Cureus Mar 2024Johanson-Blizzard syndrome (JBS) is a rare hereditary autosomal recessive disorder caused by a mutation in the ubiquitin protein ligase E3 component n-recognin 1 (UBR1)...
Johanson-Blizzard syndrome (JBS) is a rare hereditary autosomal recessive disorder caused by a mutation in the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) gene. This syndrome is characterized by the following typical clinical features: hypoplasia or aplasia of the alae nasi, congenital scalp defects, sensorineural hearing loss, hypothyroidism, growth retardation, psychomotor retardation, imperforate anus, genitourinary anomalies, and atypical hair patterns. Here, we describe a case of a 12-year-old girl with JBS of consanguineous parents. During the last trimester of pregnancy, a congenital abnormality affecting the nose was detected. Immediately after birth, the clinical examination revealed dysmorphic features in the form of hypoplastic alae nasi, microcephaly, mild hypotelorism, and cutis aplasia on the scalp. The genetic testing of the patient showed a novel sequence change mutation of the UBR1 gene (1bp duplication causing a frameshift), while both parents were carriers for this mutation. Moreover, a diagnosis of pancreatic insufficiency and subclinical hypothyroidism was made based on clinical presentation and laboratory results. The patient was started on pancreatic enzyme replacement therapy and fat-soluble vitamins, minerals, and antioxidant syrup. Further assessment revealed hypotonia, growth impairment, delay in reaching developmental milestones, and bilateral profound sensorineural hearing loss, which was managed with bilateral cochlear implantation. In addition, the patient underwent multiple craniofacial reconstructive surgeries. This case report highlights the importance of early diagnosis and multidisciplinary care of patients with JBS.
PubMed: 38606259
DOI: 10.7759/cureus.55969 -
Journal of Surgical Case Reports Mar 2024The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is a rare birth disorder involving a combination of gastrointestinal, musculoskeletal, renal,...
The omphalocele-exstrophy-imperforate anus-spinal defects (OEIS) complex is a rare birth disorder involving a combination of gastrointestinal, musculoskeletal, renal, neural, and genitourinary system defects. We present a case report of a neonate with OEIS born by vertex spontaneous delivery to non-consanguineous parents. The major presenting defect was exstrophy of the cecum lying between two exstrophied halves of the bladder, an imperforate anus and spina bifida myelomeningocele. Explorative laparotomy revealed a duplex kidney system, attachment of the terminal ileum and cecum to the exstrophy, and a sausage-like atretic large bowel. Malrotation was also noted. Ladd's bands were released followed by ileostomy and ureterostomy. Patient was stable post-operatively and in the incubator on room air. OEIS remains a challenging anomaly that requires optimal treatment to facilitate the quality of life. With appropriate surgical intervention, the functional and social treatment goals for this unusual congenital defect can be met.
PubMed: 38505329
DOI: 10.1093/jscr/rjae166 -
Case Reports in Genetics 2024Chromothripsis is characterized by shattering and subsequent reassembly of chromosomes by DNA repair processes, which can give rise to a variety of congenital...
Chromothripsis is characterized by shattering and subsequent reassembly of chromosomes by DNA repair processes, which can give rise to a variety of congenital abnormalities and cancer. Constitutional chromothripsis is a rare occurrence, reported in children presenting with a wide range of birth defects. We present a case of a female child born with multiple major congenital abnormalities including severe microcephaly, ocular dysgenesis, heart defect, and imperforate anus. Chromosomal microarray and mate pair sequencing identified a complex chromosomal rearrangement involving the terminal end of the long arm of chromosome 2, with two duplications (located at 2p25.3-p25.1 and 2q35-q37.2 regions) and two deletions (located at 2q37.2-q37.3 and 2q37.3 regions) along with structural changes including inverted segments. A review of the literature for complex rearrangements on chromosome 2 revealed overlapping features; however, our patient had a significantly more severe phenotype which resulted in early death at the age of 2 years. Breakpoints analysis did not reveal the involvement of any candidate genes. We concluded that the complexity of the genomic rearrangement and the combined dosage/structural effect of these copy number variants are likely explanations for the severe presentation in our patient.
PubMed: 38322183
DOI: 10.1155/2024/6319030 -
Journal of Medical Genetics Apr 2024Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and...
BACKGROUND
Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics.
METHODS
We screened and variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS.
RESULTS
We identified five novel and two reported pathogenic/likely pathogenic (P/LP) variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring.
CONCLUSION
This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.
Topics: Humans; Mutation; Transcription Factors; Syndrome; Hearing Loss, Sensorineural; Phenotype; Nuclear Proteins; Adaptor Proteins, Signal Transducing; Abnormalities, Multiple; Anus, Imperforate; Thumb
PubMed: 38296632
DOI: 10.1136/jmg-2023-109579 -
Medicine Dec 2023This study aimed to compare and analyze the postoperative complications and anal function after 3-stage laparoscopic-assisted anorectoplasty (LAARP) and conventional...
This study aimed to compare and analyze the postoperative complications and anal function after 3-stage laparoscopic-assisted anorectoplasty (LAARP) and conventional posterior sagittal anorectoplasty (PSARP) in the treatment of moderate to severe anal atresia in children. A total of 27 children with moderate to severe anal atresia who underwent conventional PSARP at the Dongguan Children Hospital between 2007 and 2011 were included in the control group, and 34 children with moderate to severe anal atresia who underwent 3-stage LAARP between 2012 and 2016 were included in the observation group. The incidence of postoperative complications and Kelly score of anal function in the 2 groups were statistically analyzed and the efficacy of the 2 procedures compared. The incidence of postoperative complications such as wound infection, anal stenosis, anastomotic leakage, fecal incontinence, and constipation in the LAARP group was lower as compared with the PSARP group, and there was a statistically significant difference (P < .05). There was no significant difference in the incidence of postoperative complications such as rectal prolapse, diarrhea, and recurrent fistula between the LAARP group and the PSARP group (P > .05). The Kelly score of anal function was higher in the LAARP group than in the PSARP group, and the difference was statistically significant (P < .05). Compared to conventional PSARP, laparoscopic surgery for moderate to severe anal atresia in children has less complications, improved anal function, and a clear therapeutic impact.
Topics: Child; Humans; Anus, Imperforate; Retrospective Studies; Anal Canal; Treatment Outcome; Rectum; Laparoscopy; Postoperative Complications
PubMed: 38206727
DOI: 10.1097/MD.0000000000036744