Urofacial (Ochoa) syndrome with a founder pathogenic variant in the HPSE2 gene: a case report and mutation origin.

Urofacial syndrome or Ochoa syndrome (UFS or UFOS) is a rare disease characterized by inverted facial expression and bladder dysfunction that was described for the first time in Colombia. It is an autosomal recessive pathology with mutations in the HPSE2 and LRIG2 genes. However, 16% of patients do not have any mutations associated with the syndrome. Despite the importance of neurobiology in its pathophysiology, there are no neurological, neuropsychological, or psychological studies in these patients. A 30-year-old male from Medellín, Colombia, with a significant perinatal history, was diagnosed with grade 4 hydronephrosis on his first ultrasound test. At 4 months of age, symptoms such as hypomimia, lagophthalmos, and recurrent urinary tract infections started to manifest. Imaging studies revealed urinary tract dilatation, vesicoureteral reflux, and a double collector system on his left side, which led to the diagnosis of UFS. Multiple procedures, including vesicostomy, ureterostomy, and enterocystoplasty, were performed. At 20 years of age, he achieved urinary sphincter control. Genetic analysis revealed a founder pathogenic variant, c.1516C > T (p.Arg506Ter), in the HPSE2 gene, which produces a truncated protein that lacks 86 amino acids. This variant is classified as pathogenic according to the ClinVar database for UFS. The mutation age is approximately 260-360 years, and the two alleles share a 7.2-7.4 Mb IBD segment. Moreover, we detected European local ancestry in the IBD segment, which is consistent with a Spanish introduction. Neurological examination, neuropsychological assessment, and psychological testing revealed no abnormalities, except for high stress levels. Clinical analysis of this patient revealed distorted facial expression and detrusor-sphincter dyssynergia, which are typical of patients with UFS. Genetic analysis revealed a pathogenic variant in the HPSE2 gene of European origin and a mutation age of 260-360 years. From a neurological, neuropsychological, and psychological (emotional and personality) perspective, the patient showed no signs or symptoms of clinical interest.

Ehlers-Danlos: A Literature Review and Case Report in a Colombian Woman with Multiple Comorbidities.

Ehlers-Danlos syndromes (EDS) are a heterogeneous group of genetically transmitted connective tissue disorders that directly affect collagen synthesis, with a broad range of symptoms. Case presentation: This study presents a clinical case of a Colombian woman with myopathic EDS and multiple comorbidities taking 40 years of medical history to make the right diagnosis. This article also presents a review of the current literature on EDS, not only to remind the syndrome but also to help the clinician correctly identify symptoms of this diverse syndrome. Conclusion: A multidisciplinary approach to the diagnosis of the patient, including clinical and molecular analysis, and neuropsychological and psychological assessment, is important to improve the treatment choice and the outcome prediction of the patients.

Ichthyosis: case report in a Colombian man with genetic alterations in ABCA12 and HRNR genes.

BACKGROUND: Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in the ABCA12 gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases. CASE PRESENTATION: Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found in ABCA12 and HRNR which are related to several skin diseases, including ichthyosis. CONCLUSIONS: Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.