Unilateral pulmonary agenesis with ipsilateral facial congenital anomalies in an adult with obstructive airway disease.

Pulmonary agenesis is a rare congenital anomaly which can be isolated or co-exist with other developmental defects. Boyden et al has described three degrees of mal development of lung which include agenesis, hypoplasia and aplasia. Almost all the reported cases are in paediatric age group patients while, adults with pulmonary developmental abnormalities are sparsely documented in the literature. Interestingly, adult with coexisting hemifacial anomaly and pulmonary agenesis has not been reported in the medical literature. Here, we describe a middle-aged female who initially presented with bronchial asthma and her chest radiography showed absent left lung which was later confirmed with enhanced CT imaging. Furthermore, she had ipsilateral hemi facial microsomia, microtia, facial nerve palsy and mixed sensory loss, left side large café au lait patch, splenicule and hemangioma in segment V/VI of the liver.

A novel 3q interstitial deletion including GATA2 and ZNF148: A case report.

GATA2 and ZNF148 have both been mapped to chromosome 3q. Pathogenic variants in GATA2 have been associated with immunodeficiency and high risk for myelodysplasia, acute myeloid leukemia, and chronic myelomonocytic leukemia. Gain-of-function variants in ZNF148 have previously been suggested as a mechanism for agenesis of the corpus callosum (ACC). Here, we report a novel 10.4 Mb interstitial deletion on 3q12.33q22.1 including GATA2 and ZNF148 in a child with developmental delay, agenesis of the corpus callosum, and vertebral segmentation defects. With this diagnosis, we were able to suggest preemptive referrals to hematology/oncology and allergy/immunology for close monitoring of early myelodysplasia. We also propose a possible link between ZNF148 loss of function variants and ACC.

Truncating variants of the sterol recognition region of SHH cause hypertelorism phenotype rather than hypotelorism-holoprosencephaly.

Sonic hedgehog signaling molecule (SHH) is a key molecule in the cilia-mediated signaling pathway and a critical morphogen in embryogenesis. The association between loss-of-function variants of SHH and holoprosencephaly is well established. In mice experiments, reduced or increased signaling of SHH have been shown to be associated with narrowing or excessive expansion of the facial midline, respectively. Herein, we report two unrelated patients with de novo truncating variants of SHH presenting with hypertelorism rather than hypotelorism. The first patient was a 13-year-old girl. Her facial features included hypertelorism, strabismus, telecanthus, malocclusion, frontal bossing, and wide widow's peak. She had borderline developmental delay and agenesis of the corpus callosum. She had a nonsense variant of SHH: Chr7(GRCh38):g.155802987C > T, NM_000193.4:c.1302G > A, p.(Trp434*). The second patient was a 25-year-old girl. Her facial features included hypertelorism and wide widow's peak. She had developmental delay and agenesis of the corpus callosum. She had a frameshift variant of SHH: Chr7(GRCh38):g.155803072_155803074delCGGinsT, NM_000193.4:c.1215_1217delCCGinsA, p.(Asp405Glufs*92). The hypertelorism phenotype contrasts sharply with the prototypical hypotelorism-holoprosencephaly phenotype associated with loss-of-function of SHH. We concluded that a subset of truncating variants of SHH could be associated with hypertelorism rather than hypotelorism.

Fully digital workflow of occlusal reconstruction treatment in a patient with congenital dentition defects.

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.

Mandibular Second Premolar Agenesis: A Retrospective Cross-sectional Study from Palestine.

Objectives: This retrospective study aimed to determine the prevalence of congenitally missing mandibular second premolars. Materials and Methods: A total of 1,843 radiographs were collected from five different cities in Palestine. Two experienced dentists independently examined the panoramic radiographs and demographic data (age and gender). Results: Among the 1,843 radiographs, 1,039 were for females (57.37%) and 804 were for males (43.63%); 13 cases had at least one congenitally mandibular second premolar. The prevalence of congenitally missing mandibular second premolars in the study population was 0.7%. There was no significant association between gender and mandibular second premolar agenesis. Unilateral agenesis was more common than bilateral, and the left side had more cases of congenitally missing mandibular second premolars than the right side. Conclusions: The prevalence of congenitally missing mandibular second premolars in this study population was 0.7%, within the range reported in other populations.

Assessment of fetal corpus callosum biometry by 3D super-resolution reconstructed T2-weighted magnetic resonance imaging.

Objective: To assess the accuracy of corpus callosum (CC) biometry, including sub-segments, using 3D super-resolution fetal brain MRI (SR) compared to 2D or 3D ultrasound (US) and clinical low-resolution T2-weighted MRI (T2WS). Method: Fetal brain biometry was conducted by two observers on 57 subjects [21-35 weeks of gestational age (GA)], including 11 cases of partial CC agenesis. Measures were performed by a junior observer (obs1) on US, T2WS and SR and by a senior neuroradiologist (obs2) on T2WS and SR. CC biometric regression with GA was established. Statistical analysis assessed agreement within and between modalities and observers. Results: This study shows robust SR to US concordance across gestation, surpassing T2WS. In obs1, SR aligns with US, except for genu and CC length (CCL), enhancing splenium visibility. In obs2, SR closely corresponds to US, differing in rostrum and CCL. The anterior CC (rostrum and genu) exhibits higher variability. SR's regression aligns better with literature (US) for CCL, splenium and body than T2WS. SR is the method with the least missing values. Conclusion: SR yields CC biometry akin to US (excluding anterior CC). Thanks to superior 3D visualization and better through plane spatial resolution, SR allows to perform CC biometry more frequently than T2WS.

Report of a Novel Homozygous Intragenic DCC Duplication and a Review of Literature of Developmental Split-Brain Syndrome aka Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development Syndrome.

Introduction: Horizontal gaze palsy with progressive scoliosis-2 (HGPPS2, MIM 617542) with impaired intellectual development aka developmental split-brain syndrome is an ultra-rare congenital disorder caused by pathogenic biallelic variants in the deleted in colorectal cancer (DCC) gene. Case Presentation: We report the clinical and genetic characterization of a Syrian patient with a HGPPS2 phenotype and review the previously published cases of HGPPS2. The genetic screening was performed using exome sequencing on Illumina platform. Genetic analysis revealed a novel DCC c.(?_1912)_(2359_?)dup, p.(Ser788Tyrfs*4) variant segregating recessively in the family. This type of variant has not been described previously in the HGPPS2 patients. To date, including the case reported here, three different homozygous pathogenic frameshift variants, one homozygous missense variant, and an intragenic duplication in the DCC gene have been reported in 8 patients with the HGPPS2 syndrome. Conclusion: The analysis of duplications and deletions in the DCC should be included in the routine genetic diagnostic evaluation of patients with suspected HGPPS2. This report expands the knowledge of phenotypic and genotypic spectrum of pathogenic variants causing HGPPS2.

Single-center Incidence and Patterns of Stroke in Early Renal Anhydramnios after Serial Amnioinfusions.

The Renal Anhydramnios Fetal Therapy (RAFT) trial is a study of serial amnioinfusions to prevent lethal neonatal pulmonary hypoplasia from early renal anhydramnios. Infant neurologic outcomes were not originally evaluated. We describe the high incidence of stroke observed among infants in the treatment arm of the trial at our center.

A variant of Zinner syndrome with ectopic ureteral insertion into the seminal vesicle.

Zinner syndrome comprises a triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ejaculatory duct obstruction, which can be accompanied by additional abnormalities of the genitourinary tract in some cases. Patients may be asymptomatic or present with urinary, reproductive, and/or local pain symptoms. Diagnosis is most commonly achieved via MRI. Here, we present the case of an 18-year-old male previously diagnosed with unilateral renal agenesis, who presented with testicular and penile pain, along with urinary urgency and frequency. MRI of the abdomen and pelvis revealed all three components of Zinner syndrome as well as an ectopic ureter emptying into the seminal vesicle. Our case adds to the existing limited literature on this rare syndrome and broadens the understanding of how this syndrome can present both clinically and radiologically.

Early diagnosis of solitary functioning kidney: comparing the prognosis of kidney agenesis and multicystic dysplastic kidney.

BACKGROUND: Individuals with congenital solitary functioning kidney (SFK) are at an increased risk of kidney damage. According to some studies, the risk is higher in unilateral kidney agenesis (UKA) than in unilateral multicystic dysplastic kidney (UMCDK). We hypothesized that with early detection of children with UKA and UMCDK, there would be no difference in the presence of hypertension, proteinuria, and reduced glomerular filtration rate (GFR) between UKA and UMCDK. METHODS: Based on a long-term follow-up protocol, we evaluated a cohort of 160 children followed from birth for SFK (84 with UKA and 76 with UMCDK) detected by prenatal or routine neonatal ultrasound screening. Hypertension, proteinuria, and reduced GFR were monitored as markers of kidney damage. We compared the characteristics and outcomes of the subgroups of children with UKA and UMCDK. RESULTS: GFR was reduced in 42 (26.2%) children, of whom 41 showed only mild reduction. Hypertension and proteinuria were found in 22 (13.8%) and 14 (8.8%) children, respectively. Combined kidney damage was present in 57 (35.6%) children. The UMCDK and UKA subgroups differed in GFR at final examination, with UMCDK patients being significantly more likely to have normal GFR compared to UKA patients (82% vs. 67%; p = 0.039). CONCLUSIONS: One third of the children showed signs of SFK damage, albeit mild. Patients with UKA had reduced GFR significantly more often than those with UMCDK, but did not differ in the rates of hyperfiltration injury or congenital anomalies of the kidneys and urinary tract (CAKUT) in SFK.

A 10-year-old boy with class II oligodontia treated with buccal fixed appliances and agenesis space closure of the four second premolars: Case report No. 230075 - Titularisation Collège Européen Orthodontie (CEO), European College of Orthodontics.

The patient presented in this case report is a 10-year-old boy with hyperdivergent skeletal Class II associated with familial genetic agenesis of the second premolars. The treatment plan chosen was to close the spaces of agenesis using a bimaxillary appliance fixed buccally. The advantages and disadvantages of this treatment option were discussed. The result was stable and made it possible to avoid an implant-prosthetic solution, which would undoubtedly have been more restrictive over time.

A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts.

BACKGROUND: This report presents a clinical case of syndromic rod-cone dystrophy due to a splice site variant in the ARL2BP gene causing situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts. The presence of renal agenesis and cryptorchidism expands the clinical manifestations due to ARL2BP variants. The detailed, long-term follow-up contributes valuable insights into disease progression, aiding clinical diagnosis and patient management. CASE PRESENTATION: The male patient complained of photophobia as the first symptom when he was 20 years old followed by nyctalopia, loss of central visual acuity and peripheral visual field ten years later. Genetic analysis identified a likely pathogenic homozygous variant (c.294-1G > C) involving the splicing acceptor site of intron 4. Reported symptoms together with full-field stimulus threshold testing, electroretinogram and advanced multimodal imaging allowed us to recognize the typical characteristics of a mixed retinal dystrophy. Despite the end-stage retinal disease, this patient still retained a useful residual vision at 63 years and had a slow disease progression during the last 5 years of evaluation. DISCUSSION AND CONCLUSIONS: Our findings underscore the variable clinical presentation of ARL2BP variants, emphasizing the importance of a nuanced approach in diagnosing and managing patients. The presence of renal cysts warrants consideration of a differential diagnosis, particularly with Senior-Loken (SLS), Bardet-Biedl (BBS) and Joubert syndromes (JS) but also with Short Rib Thoracic Dysplasia 9, highlighting the need for careful phenotypic evaluation in these cases.

Punctal Atresia As a Clinical Indicator of Systemic Genetic Anomalies.

BACKGROUND: Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes. METHODS: A retrospective medical records review of all patients diagnosed with PA at the Children's Hospital of Philadelphia between 2009-2023 was conducted, analyzing medical histories and genetic testing results. Primary outcomes included the prevalence of systemic syndromes, while secondary outcomes focused on the variety of associated syndromes. RESULTS: Forty-four patients were included, of which 31 were male (70%) with a mean ± SD age 3.3 ± 3.3 years. Overall, 87 puncta in the study cohort were affected, and 26 cases (59%) were bilateral. Systemic abnormalities or genetic syndromes were identified in 19 patients (43%), with the most common being Ectodermal Dysplasia and Down syndrome. Additional rare syndromes were demonstrated. No significant association was found between systemic abnormalities and gender, bilaterality, or the number of puncta involved. CONCLUSIONS: A high incidence of systemic syndromes (43%) was observed in the study cohort. In individuals with PA who also exhibit extraocular disease, systemic evaluation and genetic workup should be considered. Syndromic diagnoses identified in our cohort also include: Branchio-oto-renal syndrome, 22q11.2 deletion syndrome, 1q21.1 microdeletion syndrome, NF1, monosomy 4q and trisomy 6q, which represent novel associations. The lack of correlation between PA's phenotypic severity and systemic abnormalities highlights the need to obtain a comprehensive medical history and consider a systemic workup in PA patients.

Case report: the 'vanished' left pulmonary artery.

Background: We report a case of isolated ductal origin of pulmonary artery (DOPA) diagnosed in an asymptomatic newborn. The primary aim of this case is to highlight the need to investigate for DOPA in patients diagnosed with an 'absent branch pulmonary artery'. Case summary: Our patient was an asymptomatic newborn infant, with normal intracardiac anatomy. He was initially diagnosed post-natally with 'absent left pulmonary artery' (LPA), though the LPA was seen in antenatal scans. He underwent angiography and was re-diagnosed with bilateral arterial ducts, with ductal origin of the LPA from the left arterial duct. The LPA was salvaged by first stenting the left arterial duct on Day 11 of life, with subsequent surgery to connect the LPA to the main pulmonary artery at 4.5 months old. The patient had an uneventful recovery after the surgery. Discussion: Ductal origin of pulmonary artery is a rare vascular anomaly characterized by continuity of the left or right pulmonary artery (PA) with the distal end of the arterial duct, and discontinuity with the main PA. It is commonly misdiagnosed as pulmonary artery agenesis when the patent arterial duct constricts, with cessation of blood flow into the affected pulmonary artery. A high index of suspicion is necessary for diagnosis of DOPA. Once diagnosed, this lesion is clearly amenable to intervention, with benefits from unifocalization, to prevent late onset pulmonary hypertension or cardiac failure.

Computed tomography: Diagnostic detection of complete pericardial agenesis: A case report.

Congenital complete absence of the pericardium is a rare condition, often difficult to diagnose due to its incidental discovery or nonspecific clinical manifestations. Instrumental investigations commonly used as initial approaches, such as chest radiography and electrocardiogram, are often insufficient. Echocardiography is an imaging technique that is used for the initial evaluation of pericardial diseases. However, echocardiography does not offer a physiological anatomical delineation of the pericardium and can be affected by operator dependency, acoustic and nontraditional imaging windows. Therefore, accurate imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) are required for correct diagnosis. We present a case of a symptomatic patient with complete pericardial agenesis diagnosed on angio-CT. This case can contribute to highlighting the importance of CT as a comprehensive imaging method in diagnosis, despite MRI being the gold standard in pericardial disease assessment.

Identification and functional study of a novel variant of PAX9 causing tooth agenesis.

OBJECTIVES: To search for pathogenic gene of a family with non-syndromic tooth agenesis, and explore the possible pathogenesis. MATERIALS AND METHODS: A Chinese family with non-syndromic tooth agenesis was recruited and screened for the pathogenic variants by whole exome sequencing technology and co-segregation analysis. The subcellular localization of wild-type and mutant protein was detected by immunofluorescence assay. Cycloheximide chase assay was performed to examine the difference in degradation rate between mutant protein and wild-type one. Dual-luciferase reporter assays were conducted to explore the alterations of mutant protein in the regulation of downstream target genes. RESULTS: A novel missense variant of PAX9 (c.296C>A:p.A99D) was found in this family. Bioinformatics software showed ß-return and the random coil were shortened in the p.A99D. The variant did not affect the subcellular localization of PAX9, but the degradation rate of p.A99D was accelerated (p < 0.05). p.A99D inhibited the activation of downstream target gene BMP4 (p < 0.05). CONCLUSIONS: This novel variant expands the pathogenic gene spectrum. The variant impaired the protein structure, accelerated the degradation of protein, and inhibited the activation of the downstream target gene BMP4, an upstream molecule in the TGF-ß/BMP pathway, which may contribute to tooth agenesis in this family.

The Varieties of Ignorance: Imaging of Congenital Variants of Pancreas and Its Ductal System-A Pictorial Review.

Congenital variants of the pancreas are being increasingly detected with the widespread use of modern imaging techniques. The underlying embryologic aberration predicts the final appearance of pancreatic development. It is essential to recognize these congenital variants, as many of these have been proven to be associated with pancreatic diseases like recurrent pancreatitis and chronic abdominal pain. Cross-sectional techniques like multidetector computed tomography and magnetic resonance cholangiopancreatography are the most used imaging techniques for the pancreas, where a radiologist comes across these variants. This pictorial aims to classify the type of variant anatomy of the pancreas, their imaging appearances, and their clinical significance.

Holt-Oram Syndrome with Pulmonary Involvement-A Valuable Algorithm to Follow.

Holt-Oram syndrome comprises a rare spectrum of congenital cardiovascular and appendicular skeletal anomalies. However, only a few cases have reported lung involvement in Holt-Oram syndrome. We reported the rare case of a 1-year-old male child patient who presented with upper limb abnormalities and respiratory distress and was diagnosed with pulmonary agenesis and pulmonary arterial hypertension secondary to an atrial septal defect.

Satisfactory Outcome of Various Novel Modified Laparoscopic Neovaginoplasty Using Autologous Peritoneal Graft.

Management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome patients is by creating functional neovagina through surgical or nonsurgical route. Surgical repair using minimally invasive technique is a favorable option in creating neovagina. In this study, the patients underwent neovaginoplasty. Clinical follow-ups were done at 3, 6, and 12 months postoperatively. The primary outcomes were anatomic and functional successes; anatomical success was defined as a ≥6 cm-long neovagina that allows for easy introduction of two fingers, and functional success was defined with Female Sexual Function Index FSFI-6 questionnaire score above 19. Modified neovaginoplasty using autologous peritoneal graft was performed on the patients (n = 6). Follow-up showed mean vaginal lengths of 8.16 cm, mean surgery time of 175 min, mean blood loss of 59.17 ml, and mean duration of hospital stay of 2 days, with an average FSFI-6 score of 25,2. Therefore, we concluded that laparoscopic approach using modified technique of autologous peritoneal graft provides satisfactory result.