Comprehensive Radiological Imaging for the Characterization of Spinal Dysraphism and Associated Anomalies in a Pediatric Case.

Spinal dysraphism is a spectrum of congenital anomalies caused by incomplete neural tube closure during early development, leading to spine and spinal cord defects. These can be broadly categorized into anomalies of gastrulation (including disorders of notochord formation and integration), anomalies of primary neurulation (such as premature disjunction and nondisjunction), combined anomalies of gastrulation and primary neurulation, and anomalies of secondary neurulation. This case report focuses on a 15-year-old male patient who exhibits a range of congenital spinal anomalies of spinal dysraphism spectrum, each contributing to a complex clinical picture. The primary aim of this report is to highlight the critical role of multimodal imaging in the evaluation of such conditions. Detailed imaging studies, particularly magnetic resonance imaging (MRI), are indispensable in accurately diagnosing, guiding surgical planning, and managing the diverse anomalies associated with spinal dysraphism. In this case, imaging findings were pivotal in identifying multiple congenital abnormalities, including scoliosis, butterfly vertebrae, block vertebrae, spina bifida occulta, and diastematomyelia. These conditions pose significant diagnostic and management challenges due to their varied presentations and complications.

Molecular landscape of congenital vertebral malformations: recent discoveries and future directions.

Vertebral malformations (VMs) pose a significant global health problem, causing chronic pain and disability. Vertebral defects occur as isolated conditions or within the spectrum of various congenital disorders, such as Klippel-Feil syndrome, congenital scoliosis, spondylocostal dysostosis, sacral agenesis, and neural tube defects. Although both genetic abnormalities and environmental factors can contribute to abnormal vertebral development, our knowledge on molecular mechanisms of numerous VMs is still limited. Furthermore, there is a lack of resource that consolidates the current knowledge in this field. In this pioneering review, we provide a comprehensive analysis of the latest research on the molecular basis of VMs and the association of the VMs-related causative genes with bone developmental signaling pathways. Our study identifies 118 genes linked to VMs, with 98 genes involved in biological pathways crucial for the formation of the vertebral column. Overall, the review summarizes the current knowledge on VM genetics, and provides new insights into potential involvement of biological pathways in VM pathogenesis. We also present an overview of available data regarding the role of epigenetic and environmental factors in VMs. We identify areas where knowledge is lacking, such as precise molecular mechanisms in which specific genes contribute to the development of VMs. Finally, we propose future research avenues that could address knowledge gaps.

An Incidental Finding of Butterfly Vertebrae in a Case of Vertebral Defects, Anal Atresia, Cardiac Defects, Tracheo-Esophageal Fistula, Renal Anomalies, and Limb Abnormalities (VACTERL).

Butterfly spine is a rare benign congenital abnormality. The onset of a minimum of three of the congenital malformations of vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities often characterises the VATER/VACTERL relationship. Recognising this anomaly is crucial for diagnosis, although this rare aberration is thought to be asymptomatic most of the time. Here we are describing a case of a one-year-old female child who has tetralogy of Fallot, congenital anal atresia, vesicovaginal fistula, and butterfly vertebrae which were found as an incidental finding. Furthermore we suggest screening all the children with any one abnormality of VACTERL, usually vertebral anomalies are screened.

A rare incidental finding of an isolated S1 butterfly vertebra: A case report.

Butterfly vertebra is an uncommon type of vertebral anomaly (sometimes referred to as a sagittal cleft vertebra or an anterior rachischisis) caused by persistent notochordal tissue. Butterfly vertebrae of S1, which is rarer anomaly compared to thoraco-lumbar region, may be associated with syndromic causes and usually asymptomatic with a funnel shaped defect seen in imaging which can later give rise to disk problems, facet joint degeneration and chronic low back pain. We here share a case of 35-year female presented with intermittent low back pain diagnosed with S1 butterfly vertebrae as an incidental finding in radiograph and magnetic resonance imaging. Radiologist and orthopedicians should be vigilant about this rare entity as a differential of low back pain and its association with other syndromes.

Phenotypic Variability of MEGF10 Variants Causing Congenital Myopathy: Report of Two Unrelated Patients from a Highly Consanguineous Population.

Congenital myopathies are rare neuromuscular hereditary disorders that manifest at birth or during infancy and usually appear with muscle weakness and hypotonia. One of such disorders, early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD, OMIM: 614399, MIM: 612453), is a rare autosomal recessive disorder caused by biallelic mutations (at homozygous or compound heterozygous status) in MEGF10 (multiple epidermal growth factor-like domains protein family). Here, we report two unrelated patients, who were born to consanguineous parents, having two novel MEGF10 deleterious variants. Interestingly, the presence of MEGF10 associated EMARDD has not been reported in Saudi Arabia, a highly consanguineous population. Moreover, both variants lead to a different phenotypic onset of mild and severe types. Our work expands phenotypic features of the disease and provides an opportunity for genetic counseling to the inflicted families.

Alagille syndrome caused by NOTCH2 mutation presented atypical pathological changes.

BACKGROUND: Alagille syndrome (ALGS) is a rare multisystem disorder caused by mutations in the JAG1 or NOTCH2 gene. However NOTCH2 gene mutations were rarely found in the Alagille patients. Little is known about the clinical and pathological profiles about Alagille patients with NOTCH2 mutation. CASE REPORT: Our case described a 16-year-old female patient manifesting as recurrent jaundice and abnormal liver function from the second week of her birth. She presented a butterfly vertebrae and typical facial features including a prominent forehead, deep-set eyes, a pointed chin, and a straight nose with bulbous tip. Pathogenic heterozygous c.5857 C > T variant in NOTCH2 gene was found. Her liver biopsy featured by a disorder liver structure with cholestasis and fibrosis in portal area, which is different from typical bile duct paucity reported in JAG1 deficient patients. RESULTS: A diagnosis of ALGS was made. The patient was treated with ursodeoxycholic acid and compound embryonic bovine liver extract tablets and infusion of human serum albumin to improve her clinical and pathological symptoms. CONCLUSION: Since Alagille patients with NOTCH2 mutations have been rarely reported, our case will highlight the clinical and pathological profiles of these patients.

Multi-level sagittally cleft vertebrae: a case report and review of the literature.

The term "sagittal cleft vertebra" (SCV) denotes a rare embryologically derived longitudinal defect within the vertebral body, which is clinically and radiologically challenging to diagnose in isolation. This defect results in two hemivertebrae, which ossify discordantly, ultimately leading to a sagittal cleft through the vertebral body. Often presenting with low back pain or concomitant with an associated syndromic illness, SCV is often found incidentally and can mimic vertebral compression fractures radiographically. Treatment of SCV has largely been conservative and symptomatic. With only 109 reported cases in the current literature, we present a unique case of multiple SCV throughout the thoracolumbar region in an adolescent patient. We performed a review of the literature to identify published cases of SCV to date. We searched PUBMED using the terms "sagittal cleft vertebrae", "butterfly vertebrae", and "anterior rachischisis". Abstracts were screened for reports specifically involving original cases of SCV. Given the well-established association with syndromic illnesses, finding an SCV warrants further investigation for other abnormalities of the musculoskeletal, cardiac, and genitourinary systems. Complex management strategies are rare unless the SCV is associated with an aberrant syndrome, disc herniation or severe musculoskeletal abnormality, or symptomatic disc herniation requiring surgical management. Further studies should focus on uncovering the genetic markers leading to the cleft vertebral bodies, with a focus on early screening and monitoring of patients who could be predisposed to the condition.

Precise breakpoint detection in a patient with 9p- syndrome.

We present a case of 9p- syndrome with a complex chromosomal event originally characterized by the classical karyotype approach as 46,XX,der(9)t(9;13)(p23;q13). We used advanced technologies (Bionano Genomics genome imaging and 10× Genomics sequencing) to characterize the location of the translocation and accompanying deletion on Chromosome 9 and duplication on Chromosome 13 with single-nucleotide breakpoint resolution. The translocation breakpoint was at Chr 9:190938 and Chr 13:50850492, the deletion at Chr 9:1-190938, and the duplication at Chr 13:50850492-114364328. We identified genes in the deletion and duplication regions that are known to be associated with this patient's phenotype (e.g., ZIC2 in dysmorphic facial features, FOXD4 in developmental delay, RNASEH2B in developmental delay, and PCDH9 in autism). Our results indicate that clinical genomic assessment of individuals with complex karyotypes can be refined to a single-base-pair resolution when utilizing Bionano and 10× Genomics sequencing. With the 10× Genomics data, we were also able to characterize other variation (e.g., loss of function) throughout the remainder of the patient's genome. Overall, the Bionano and 10× technologies complemented each other and provided important insight into our patient with 9p- syndrome. Altogether, these results indicate that newer technologies can identify precise genomic variants associated with unique patient phenotypes that permit discovery of novel genotype-phenotype correlations and therapeutic strategies.

Butterfly Vertebrae: A Systematic Review of the Literature and Analysis.

STUDY DESIGN: Systematic review (Level 4). OBJECTIVE: To summarize the demographics, clinical presentations, and conditions associated with butterfly vertebrae. METHODS: A systematic search was performed of multiple databases. A total of 279 articles were identified for screening. Case series or case reports of butterfly vertebrae with adequate clinical detail were complied. RESULTS: Eighty-two total articles (109 patients) were selected for final inclusion. Sixty-one percent of patients presented with a single butterfly vertebra, while 39% were multiple. The most common location for butterfly vertebrae was T1. Fifty-six percent of cases were associated with a syndrome, the most common being spondylocostal dysostosis. The presence of multiple butterfly vertebra was strongly associated with a syndrome or additional anomalies (P < .001). Overall, the most common presenting complaint was low back pain. Seventy percent of patients had associated spinal disease. Other organ systems affected included musculoskeletal (43%), craniofacial (30%), neurologic (27%), cardiovascular (24%), genitourinary (23%), gastrointestinal (22%), laboratory abnormality (16%), and endocrine (9%). CONCLUSIONS: This study is the largest collection of butterfly vertebrae cases to date. Butterfly vertebrae are associated with spinal deformity and multiple butterfly vertebrae may indicate a syndromic illness. Low back pain or disc herniation may occur with lumbar butterfly vertebrae however the etiology of this phenomena has not been rigorously explained. Many diseases and syndromes are associated with butterfly vertebrae.

Sacral butterfly vertebrae in the setting of a sacral fracture and unstable pelvic ring injury: A case report and review of the literature.

Butterfly vertebrae are rare developmental anomalies representing failure of formation of the vertebral body. There have only been 8 previous reports of a butterfly vertebra occurring at S1. This is the first described case of a butterfly vertebra presenting with a sacral fracture and pelvic ring injury.

JAGGED1 gene variations in Chinese twin sisters with Alagille syndrome.

Variations in the JAGGED1 gene have been found to cause Alagille syndrome. Nevertheless, no particular hotspots in the gene have been found; any part of the entire coding regions for JAGGED1 may be involved. Twin sisters with jaundice visited our hospital and were diagnosed with Alagille syndrome. The gene variations in their JAGGED1 coding sequences were evaluated by complementary DNA sequencing. The 12-month-old twin sisters have broad foreheads, deep-set eyes, pointed chins, and triangular faces with jaundice. Clinical testing showed the presence of posterior embryotoxon, butterfly vertebrae, and atrial septal defect. Biochemical indexes showed cholestasis and liver damage. Three conserved variations were identified within exons 22 (c.2612C>G), 24 (c.2957T>A), and 26 (c.3417T>C) in the JAGGED1 coding sequence. The predicted consequences for c.2612C>G, c.2957T>A, and c.3417T>C were p.Pro871Arg, p.Leu986*, and p.Tyr1139=, respectively. The T to A change in the JAGGED1 coding sequence at 2957 will generate a stop codon and might lead to deletion of amino acid 233 at the C terminal of the JAGGED1 protein. Our data suggest that gene variations of c.2612C>G, c.2957T>A, and c.3417T>C, especially c.2957T>A, might have contributed to the pathogenesis of Alagille syndrome in these Chinese twin sisters and provided new gene evidences for Alagille syndrome.

Two- and three-dimensional prenatal sonographic diagnosis of Alagille syndrome.

We describe a case of Alagille syndrome diagnosed by second-trimester ultrasound. Features included the characteristic prominent chin, single umbilical artery, and hemivertebrae. Three-dimensional imaging demonstrated classic butterfly vertebrae, which were not otherwise appreciable. Alagille syndrome may be detected by second-trimester ultrasound in the at-risk fetus.