Complete diphallia associated with unusual multiple congenital anomalies: case report and review of literatures

Background Diphallus (duplication of phallus) is rarely encountered in surgical practice with only 100 cases reported in literature. Some cases may be isolated but mostly associated with other anomalies, without clear data about its etiology. Case presentation We reported a 1-day-old newborn baby who was presented with complete duplication of the phallus, one of them being hypospadic associated with a high type imperforate anus, omphalocele, congenital pouch colon, sacral meningocele, and other congenital anomalies not reported before in such combinations. Multiple stages surgical corrective procedures were performed over a period of 4 years with 4–6 months interval between each stage, starting with the management of omphalocele and colostomy, ended by excision of the abnormal phallus with abdominoplasty and closure of colostomy. The outcome was evaluated, and literatures were reviewed in relation to types, presentations, and options for surgical correction with optimal outcomes. Conclusion A combination of diphallia and other abnormalities in our patient are not reported previously in such manner and were very difficult to be corrected. Only expert pediatric surgeons should treat such conditions as every case is unique in nature. In all conditions, the abnormal phallus should be excised, and the final aim is to achieve a continent child with cosmetically acceptable genitalia.

A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses. Case Report and Review of the Literature

We present a complex chromosomal anomaly identified using cytogenetic and molecular methods. The child was diagnosed during the neonatal period with a multiple congenital anomalies syndrome characterized by: flattened occipital region; slight turricephaly; tall and broad forehead; hypertelorism; deep-set eyes; down slanting and short palpebral fissures; epicanthic folds; prominent nose with wide root and bulbous tip; microstomia; micro-retrognathia, large, short philtrum with prominent reliefs; low set, prominent ears; and congenital heart disease. The GTG banding karyotype showed a 46,XY,der(10)(10pter→10q26.2::4q26→4qter) chromosomal formula and his mother presented an apparently balanced reciprocal translocation: 46,XX,t(4;10)(q26;q26.2). The chromosomal anomalies of the child were confirmed by MLPA, and supplementary investigation discovered a quadruplication of the 4q35.2 region. The mother has a triplication of the same chromosomal fragment (4q35.2). Using array-CGH, we described the anomalies completely. Thus, the boy has a 71,057 kb triplication of the 4q26–q35.2 region, a 562 kb microdeletion in the 10q26.3 region, and a 795 kb quadruplication of the 4q35.2 region, while the mother presents a 795 kb triplication of the 4q35.2 region. Analyzing these data, we consider that the boy’s phenotype is influenced only by the 4q partial trisomy. We compare our case with similar cases, and we review the literature data.

Spondylocostal Dysplasia and Brachydactyly: a case report

We report a preterm male neonate presenting with a skeletal dysplasia associated with multiple congenital anomalies. Radiologic findings and genetic studies are consistent with spondylocostal dysostosis (SCD) and autosomal dominant brachydactyly. This is the first case report of spondylocostal dysostosis and brachydactyly associated with TBX6 and IHH variants.

Management and Outcome of a Neurologically Intact Infant with Pierre Robin Sequence and Dandy-Walker Variant Diagnosed with Large Hemispheric Brain Abscess – Case Report

Pierre Robin sequence (PRS) is a condition consisting of three essential components: micrognathia or retrognathia, cleft palate, and glossoptosis. It can be part of multiple congenital anomalies. We present the case and outcome of a 3-month-old clinically stable patient who has PRS with Dandy-Walker variant – which is a rare presentation in the literature – with a large right hemispheric brain abscess, treated with multiple minimally-invasive surgical drainage procedures with adjuvant antibiotics.

Familial Translocation t(2;4) (q37.3;p16.3), Resulting in a Partial Trisomy of 2q (or 4p) and a Partial Monosomy of 4p (or 2q), Causes Dysplasia

Background: Wolf-Hirschhorn syndrome, a well-known contiguous microdeletion syndrome, is caused by deletions on chromosome 4p. While the clinical symptoms and the critical region for this disorder have been identified based on genotype-phenotype correlations, duplications in this region have been infrequently reported.Conclusion: Our case report shows that both deletions and duplications of the Wolf-Hirshhorn critical region cause intellectual disability/developmental delay and multiple congenital anomalies.

A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies

Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.

1067 Neoplasia in Association with a Congenital Anomaly: Wilms Tumor in a Horseshoe Kidney

Introduction Horseshoe malformation is the most common form of fusion defects involving the kidney, whereas Wilm's tumor is the most common primary malignant renal tumor in children. The co-incidence of these two pathologies gives off an incidence rate of 0.48%. Case Report This is a case of a two-year-old female who presented early in life with multiple congenital anomalies including congenital heart disease, bilateral aniridia, persistent thrombocytopenia, and sickle cell trait in association with a painless abdominal mass. A CT scan showed a horseshoe kidney. The patient was lost for follow up until the age of two years, in which another CT scan revealed a left lower pole focal cystic mass measuring 5.1x5.3x6.3cm. WAGR syndrome was suspected and confirmed through genetic testing. A multidisciplinary approach was necessary to manage her efficiently due to the numerous co-existing congenital pathologies. The patient underwent six cycles of chemotherapy leading to a 35% reduction in tumor size and a left nephrectomy. She was admitted to the pediatric ICU post-operatively for observation. Histopathological analysis revealed features of stage two stromal type nephroblastoma. Her renal function and urine output were satisfactory throughout the duration of her admission as well as on follow up. Conclusions Keeping a high index of suspicion is imperative; individuals with renal anomalies, namely horseshoe kidney in the context of WAGR syndrome, mandate a comprehensive assessment through clinical examination, laboratory workup, and imaging. Though different approaches to standard Wilm's tumor cases have been explored thoroughly, it is crucial to keep in mind the need for multidisciplinary involvement in patients with multiple congenital anomalies.

Diaphragmatic Hernia as a Prenatal Feature of Glycosylphosphatidylinositol Biosynthesis Defects and the Overlap With Fryns Syndrome – Literature Review

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome, with diaphragmatic defects and secondary lung hypoplasia as cardinal features. Despite it was reported first in 1979, its exact etiology has not been established to date. With this review, we would like to draw attention to the prenatal presentation of multiple congenital anomalies syndromes, resulting from defects in the synthesis of glycosylphosphatidylinositol anchors, to be considered in a prenatal assessment of fetuses with DH and Fryns-like phenotype.