Vanessa Isabel Romero

Disorders of the phenylalanine–tyrosine–catecholamine axis are a clinically relevant group of neurometabolic conditions in which pathogenic variants in key enzymes impair dopamine and norepinephrine biosynthesis. Patients may present with movement disorders, autonomic dysfunction, developmental delay, and related neurobehavioral manifestations. In this narrative review, we synthesize the main enzymatic defects across the axis, focusing on phenylalanine hydroxylase, tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase. We describe how diagnostic practice has evolved from isolated biochemical assays to integrated approaches that link clinical phenotyping with targeted biochemical profiling and molecular confirmation. Genetic testing now supports diagnosis, treatment planning, and family counseling, while chromatographic and mass spectrometry-based methods remain essential for quantifying amino acids and neurotransmitter-related metabolites. We also discuss emerging biosensor-based strategies as a potential route to decentralized and minimally invasive monitoring.

Cleft lip with or without cleft palate (CL ± P) is a common congenital anomaly with complex genetic origins. This study presents a genetic case series of three Ecuadorian families with non-syndromic cleft lip and/or palate analyzed using whole-exome sequencing (WES). We identified rare or novel variants in genes with established or emerging roles in craniofacial development. Bioinformatic analyses—while not supported by functional validation—helped prioritize several candidate variants, including a novel KIF7 variant. These findings provide exploratory genetic data from an underrepresented Latin American population and highlight the need to include diverse cohorts in genomic research to improve diagnosis and genetic counseling. The online version contains supplementary material available at 10.1186/s12903-026-07796-8.

Wilson disease is a rare autosomal recessive disorder caused by variations in ATP7B, leading to copper accumulation and multisystemic damage. Diagnosis is

This case report presents two Ecuadorian patients with Rothmund-Thomson syndrome type 2 (RTS2), an autosomal recessive disorder, who share a RECQL4 variant previously identified in another Ecuadorian patient, supporting the recurrent presence of this variant in the Ecuador population. Additionally, in the Case 2 patient with a suspected compound heterozygosity, a second pathogenic variant was identified that had not been previously reported in Ecuador. These findings underscore the importance of molecular diagnosis for accurate classification of RTS2, informed risk assessment, and improved clinical care, particularly in underrepresented populations.

Breast cancer is the most frequent gynecological malignancy and the main cause of cancer death in the female population worldwide. One of the most significant challenges in its clinical management is the molecular heterogeneity of malignant breast tumors, which is reflected in the current molecular classification of these entities. In each of these tumor molecular subtypes, distinct genetic alterations are involved, and several intracellular signaling pathways contribute to defining their biological identity and clinical response. This literature review summarized the main classic and emerging biomarkers in breast cancer, along with the therapies associated with them. There are several classic biomarkers associated with this disease, such as estrogen and progesterone receptors, the HER2 receptor, and the Ki-67 cell proliferation marker. Given the limitations of these biomarkers, new biomarkers have been identified, including the TP53 tumor suppressor gene, the EGFR, different types of RNAs, plus epigenetic and immunological biomarkers. The integration of classic and emerging biomarkers along with new therapeutic targets in the clinical practice has promoted a thorough understanding of the high molecular complexity of breast cancer and the development of precision medicine strategies which increase the chances of therapeutic success.

Chromosomes 3 and 8 harbor genes essential for neurodevelopment, skeletal formation, and metabolic regulation. We report a case of two half-siblings with neurodevelopmental delay and intellectual disability who inherited a derivative chromosome 3 from their asymptomatic mother. Chromosomal microarray analysis first identified a 7.12 Mb deletion in 3p26.3–p26.1 and a 48.86 Mb duplication in 8q22.1–q24.3, and findings were further characterized by whole genome sequencing and manual structural interpretation. The 3p deletion involved four pathogenic genes ( CHL1, CNTN6, CNTN4, ITPR1 ) associated with cognitive impairment, ataxia, and motor dysfunction. The 8q duplication affected 50 dosage-sensitive genes implicated in developmental and neurological disorders. Together, these chromosomal imbalances explain the siblings’ phenotype and underscore the contribution of gene dosage effects to neurodevelopmental disease. This case highlights the utility of combining chromosomal microarray and genome sequencing in the diagnosis of complex rearrangements and emphasizes the importance of early genetic counseling and intervention.

Persistent infection with oncogenic human papillomavirus (HPV) types, such as HPV 16 or 18, is a major factor in cervical cancer development. However, only a small percentage of infected women develop cancer, indicating that other factors are involved. Emerging evidence links vaginal microbiota with HPV persistence and cancer progression. Alterations in microbial composition, function, and metabolic pathways may contribute to this process. Despite the potential of metagenomics to explore these interactions, studies on the vaginal microbiota’s role in cervical cancer are limited. This review systematically examines the relationship between cervical microbiota, HPV, and cervical cancer by analyzing studies from PubMed, EBSCO, and Scopus. We highlight how microbial diversity influences HPV persistence and cancer progression, noting that healthy women typically have lower microbiota diversity and higher Lactobacillus abundance compared to HPV-infected women, who exhibit increased Gardenella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., associated with dysbiosis. We discuss how microbial diversity is associated with HPV persistence and cancer progression, noting that studies suggest healthy women typically have lower microbiota diversity and higher Lactobacillus abundance, while HPV-infected women exhibit increased Gardnerella, Prevotella, Sneathia, Megasphaera, Streptococcus, and Fusobacterium spp., indicative of dysbiosis. Potential markers such as Gardnerella and Prevotella have been identified as potential microbiome biomarkers associated with HPV infection and cervical cancer progression. The review also discusses microbiome-related gene expression changes in cervical cancer patients. However, further research is needed to validate these findings and explore additional microbiome alterations in cancer progression.

Background: Delays in diagnosing rare genetic disorders often arise due to limited awareness and systemic challenges in primary care. This case highlights the importance of a holistic approach to patient care, encompassing timely detection and comprehensive evaluation of clinical features.Methods: We report the case of a 21-year-old Ecuadorian male with facial and hand dysmorphias, cardiomegaly, pulmonary hypertension, and patent ductus arteriosus (PDA). Whole-exome sequencing, performed using the Illumina NextSeq platform. We extensively analyzed over 100 genes linked to congenital structural heart diseases.Results: The genetic findings provided a definitive diagnosis of Craniofacial-Deafness-Hand Syndrome, an extremely rare autosomal dominant condition, but found no variants that explain the patient’s cardiac phenotype. We identified a novel pathogenic missense variant in the PAX3 gene (c.A91C, p. T31P).Discussion and conclusions: This case underscores the necessity of integrating genetic testing into routine clinical practice to enhance diagnostic precision for rare diseases. It also highlights the need for multidisciplinary collaboration and a holistic care model to improve patient outcomes. The unique association of Craniofacial-Deafness-Hand Syndrome with cardiovascular anomalies due to a PAX3 variation provides valuable insights into the genetic underpinnings of this rare condition.

La carta al editor sobre la composición genética de la población ecuatoriana ofrece importantes aportes al conocimiento de la diversidad genética del país1. El estudio utiliza 46 marcadores AIM-InDels, proporcionando una estimación valiosa del mestizaje en tres regiones clave: Amazonía, Costa y Sierra. Este enfoque permite visualizar cómo la ascendencia nativa americana, europea y africana varía según las diferentes zonas, lo que refleja parte de la compleja historia de Ecuador. Sin embargo, me gustaría señalar algunas limitaciones y áreas donde una mayor investigación podría enriquecer estos hallazgos.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency in the phenylalanine hydroxylase (PAH) enzyme, leading to the accumulation of phenylalanine and its metabolites, which are toxic to the central nervous system. Without treatment, PKU can result in severe intellectual disability and neurological issues. This study aims to present the first cohort of clinically described Ecuadorian PKU patients, analyzing genotype-phenotype correlations and comparing these variants with global databases to improve diagnosis and treatment in Ecuador. Detailed clinical histories were collected, and an analysis of genotype versus phenotype (affected protein domain) of the variant was performed. Among the PAH genotypes identified, we found 15 distinct variants, with c.[754 C > T](p.Arg252Trp); [754 C > T](p.Arg252Trp) being the most frequent genotype (23.68%), followed by c.[1045T > C](p.Ser349Pro); [1045T > C](p.Ser349Pro) (15.79%) and c.[441 + 5G > T]; [754 C > T](p.Arg252Trp) (13.16%). Additionally, several unique genotypes were identified, such as c.[140G > A](p.Ala47Val); [140G > A](p.Ala47Val) and c.[331 C > T](p.Arg111Ter); [1243G > A](p.Asp415Asn), which are not commonly reported in other populations. Most genotypes were heterozygous (63.2%). The majority of variants were missense variants (66.6%) affecting the catalytic domain (53.3%). The highest phenylalanine levels were found in patients with c.[754 C > T](p.Arg252Trp); [754 C > T] (p.Arg252Trp) (2700 umol/L). Phenotypic data were available for 11 patients, showing 45.45% with classic PKU, 45.45% with mild hyperphenylalaninemia, and 9% with mild PKU. There was a 63.6% concordance with the BIOPKU database. Five low-frequency genotypes not reported in BIOPKU were identified, suggesting unique regional variants. Our study highlights the genetic complexity of PKU in Ecuador, with a high prevalence of unique variants not commonly found in other regions. This underscores the necessity for region-specific genetic analysis to improve PKU diagnosis and treatment. The findings emphasize the importance of tailored therapeutic strategies and continued research to enhance outcomes for PKU patients in Latin America.