Modification of Pelvic Support Osteotomy Technique in Patients with Sequelae of Hip Dysplasia: A Case Series.

Introduction: The management of hip dislocation in patients older than 9 years of age is a challenge in terms of deciding which is the best treatment course to follow since the main sequelae are as follows: pain, discrepancy in the length of the pelvic extremities and lame gait, with the consequent disability for activities of daily living. In Ho Choi, Thabet A mention limited treatment options, including total hip arthroplasty and hip arthrodesis. These options have their benefits and limitations. The pelvic support osteotomy initially indicated for the treatment of septic arthritis of the hip and performed for the first time by Bavoier in 1838 and modified in 1970 by Ilizarov aims to improve the aforementioned sequelae. These cases report showed us the functional improvement with the treatment of dislocated hip dysplasia with pelvic support osteotomy with monolateral fixator and the 2nd osteotomy 4 cm distal to the hip. This was corroborated through the application of the modified Harris test. Case Report: A series of six female Mexican adolescent patients from 11 to 17 years of age who come to the clinic due to long-standing pain symptoms in the coxofemoral joint, three patients in the right and three in the left hip when walking. All were treated with pelvic support osteotomy. The six patients continued with mild positive Trendelenburg but all of them diminished the discrepancy in the pelvic extremities, the mobility arcs were preserved and pain was suppressed in all. The modified Harris test showed increased scores (103.3%) after the surgery. There was just a minor complication in a patient, and it was resolved with surgical lavage. Conclusion: The modifications in the technique, monolateral fixator and second osteotomy 4 cm from the first one, allowed our patients to present functional improvement at the hip, which was assessed with the modified Harris scale. Patients achieved independent walking without pain and Trendelenburg less evident. The changes we found in our patients are evidence of the goodness and effectiveness of this type of osteotomy in patients older than 9 years of age, to improve the function of the hip.

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.

Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.

Sordera neurosensorial congénita con malformación de oído interno ligada al X en una familia mexicana / Congenital sensorineural deafness X-linked, with inner ear malformation in a Mexican family

Introducción. Las sorderas o hipoacusias prelinguales son de etiología genética entre el 60 y el 68% de los casos; de estos, del 20 al 40% son malformaciones del oído interno. De los casos de hipoacusia no sindrómica ligada al X se han descrito siete tipos. De las malformaciones de oído interno, la partición coclear incompleta tipo III es la menos frecuente.Objetivo. Presentar el reporte clínico-genético de una familia mexicana, con indi-viduos varones afectados por sordera neurosensorial congénita con malformación de oído interno. Material y Métodos. Se realizó estudio de una familia en la que nueve miembros presentaban sordera. Se estudiaron cuatro de ellos y una madre sin manifestaciones, a través del estudio clínico general por médico genetista, el estudio audiológico (otos-copía y audiometría) por médico audiólogo y el estudio de tomografía computada (TC) por médico radiólogo.Resultados. Los pacientes estudiados presentaron sordera neurosensorial congéni-ta, de severa a profunda bilateral. A través de la TC, se evidenció malformación de oído interno. Tres pacientes presentaron partición coclear incompleta tipo III y un paciente partición incompleta tipo I. Debido al estudio clínico y al árbol genealógico, se definió diagnóstico de hipoacusia neurosensorial no sindrómica ligada al X. La TC de la madre sin manifestaciones no presentó evidencia de malformaciones en oído interno (MOI).Conclusión. El estudio de imagen es fundamental para definir presencia o no de MOI en todos los pacientes con hipoacusia y así poder guiar la terapéutica y el aseso-ramiento genético, así como realizar los estudios moleculares más adecuados

Introduction. The pre-lingual deafness or hearing loss are of genetic cause in be-tween 60% and 68% of cases, among these, between 20% and 40% are malforma-tion of the inner ear. From the non-syndromic hearing loss cases that are linked to the X chromosome, seven types have been described. Among these inner ear malforma-tions, incomplete cochlear partition type III is the less frequent.Objective. Present the clinical genetical report of a Mexican family, with male in-dividuals affected by congenital neurosensory deafness with inner ear malformation.Materials and methodology. A study on a family in which nine members were affected by deafness was done. Four of them, plus a mother without manifestation, were studied through a general clinical study by a geneticist, an audiological study (otoscopy and audiometry) by an audiologist, and a computed tomography (CT) scan by a radiologist.Results. The studied patients presented congenital neurosensory deafness, from se-vere to deep bilateral. Via the CT, the inner ear malformation was made clear. Three of the patients presented incomplete cochlear partition type III and one patient in-complete cochlear partition type I. Due to the clinical study and the family tree, it was diagnosed non-syndromic neurosensory deafness linked to X. The CT of the mother without manifestation did not show evidence of inner ear malformations.Conclusion. The study by image is fundamental to define whether there is or not a presence of inner ear malformations in any patient with heading loss to be able to guide the therapeutics and the genetic counseling, as well as to make more accurate molecular studies

Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort.

OBJECTIVES: The genetics of sensorineural hearing loss is characterized by a high degree of heterogeneity. Despite this heterogeneity, DNA variants found within SLC26A4 have been reported to be the second most common contributor after those of GJB2 in many populations. METHODS: Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed. RESULTS: We identified 27 unique SLC26A4 variants in 31 probands. The variants c.1673A > G (p.N558S), c.1708-1G > A, c.1952C > T (p.P651L), and c.2090-1G > A have not been previously reported. The p.N558S variant was detected in two unrelated Mexican families. CONCLUSION: A range of SLC26A4 variants without a common recurrent mutation underlies SLC26A4-related hearing loss in Turkey, Iran, and Mexico.

PPARG-LYPLAL1 Multi-Allelic Combination Associated with Obesity and Overweight in Mexican Adolescent Females.

OBJECTIVE: We studied multi-loci variants to identify the contribution of six candidate genes (ADIPOQ, CDH13, LYPLAL1, MC4R, PPARG and PGC1A) in the development of obesity and overweight. DESIGN: We genotyped 404 chromosomes with eleven SNPs in Mexican female adolescents, who were subdivided into two groups (obesity-overweight and normal-weight) using the World Health Organization parameters. Genomic (800 chromosomes) and ancestral (208 chromosomes) controls were included to reduce the population bias. Anthropometric measurements, biochemical parameters, and caloric intake were obtained only in the groups of Mexican female adolescents. RESULTS: A positive genotype-phenotype association was found that involves the multi-allelic combination of three risk alleles (one in PPARG and two in LYPLAL1) with obesity and overweight (OR=3.1, P=.010). This combination also exhibited a significant association with waist circumference (P=.030) and triglycerides levels (P=.030). These associations were supported by a logistic regression analysis adjusted for several confounding variables. CONCLUSIONS: Our data suggest the joint participation of PPARG-LYPLAL1 genes in metabolic disorders development. Hence, these genes could act as potential biomarkers in obesity and overweight. Our findings underscore the complexity of metabolic disorders and provide evidence about the importance of multi-loci analysis to study complex diseases.

Leiden V factor and spastic cerebral palsy in Mexican children.

AIM: Cerebral palsy (CP) is a persistent motor disorder that appears before the patient is 3 years old due to a nonprogressive interference in the brain's development which takes place before the central nervous system growth is complete. Causes of this have been studied, and one that has been proposed for spastic hemiparesis CP is the Leiden mutation of V factor coagulation. We want to know whether this mutation can cause CP in our population. MATERIALS AND METHODS: We carried out a study of cases and controls with 94 patients with spastic hemiparesis CP and 120 controls as well as their mothers with their controls. RESULTS: None of the patients, their mothers, or controls had the Leiden mutation; however, other risk factors were significant: hypoxia odds ratio (OR) 7.189 (2.546, 20.302) p=0.0001, smoking OR 16.621 (2.945, 93.818) p=0.001, maternal infections (urinary or vaginal) OR 7.040 (2.952, 16.789) p=0.0001, weeks of gestation OR 0.866 (0.7750, 0.999) p=0.048, and maternal age OR 1.114 (1.031, 1.204) p=0.006. CONCLUSION: Leiden mutation of factor V is not an important factor for our Mexican mestizo population; however, there are other important perinatal risk factors.

Association of resistance to activated protein with the presence of Leiden and Cambridge Factor V mutations in Mexican patients with primary thrombophilia.

BACKGROUND: Leiden and Cambridge factor V coagulation mutations and activated protein C resistance (RaPC) are alterations related with vein and artery thrombosis. In this study we aimed to determine whether RaPC is associated with the presence of Leiden and Cambridge mutation and the frequency of these mutations in the racially mestizo Mexican population. METHODS: We included 150 Mexican patients with primary thrombophilia and 100 healthy subjects in this study. RaPC was determined using commercial methods and genotypes FV Leiden and FV Cambridge with PCR-RFLPs. RESULTS: RaPC was positive in four patients and in one control individual; however, there was no presence of Leiden or Cambridge mutation in the studied group; thus, RaPC was not correlated with the presence of any of the studied mutations. CONCLUSIONS: These results indicate that there are other primary or secondary causes different from those studied, which condition the presence of RaPC. Furthermore, the frequency obtained for RaPC in our thrombophilic population of racially mixed Mexicans is lower compared to that obtained in the Caucasian population, most probably because they are genetically different populations.

Asociación de la RPCA con mutaciones Leiden y Cambridge del factor V de la coagulación en pacientes mexicanos con trombofilia primaria / Association of resistance to activated protein with the presence of Leiden and Cambridge Factor V mutations in Mexican patients with primary thrombophilia

Introducción: Las mutaciones Leiden y Cambridge del factor V de la coagulación y la resistencia a la proteína C activada (RPCA) son alteraciones que se relacionan con trombosis venosa y arterial. En este trabajo se analizó si la RPCA está asociada con las mutaciones Leiden y Cambridge, y la frecuencia de éstas en población mestiza mexicana. Material y métodos: Se incluyeron 150 pacientes mexicanos con trombofilia primaria y 100 sujetos sanos. Se determinó la RPCA empleando método comercial y los genotipos factor V Leiden y factor V Cambridge mediante PCR-RFLPs. Resultados: La RPCA fue positiva en cuatro pacientes y en un individuo control; sin embargo, no se encontró la mutación Leiden o Cambridge en la población estudiada, por lo que la RPCA no se correlacionó con ninguna de las mutaciones investigadas. Conclusiones: Los resultados indican que existen otras causas primarias o secundarias diferentes a las analizadas, que condicionan la RPCA. Además, la frecuencia obtenida para la RPCA en nuestra población trombofílica mestiza mexicana fue menor comparada con la obtenida en población caucásica, quizá por tratarse de poblaciones genéticamente diferentes.

BACKGROUND: Leiden and Cambridge factor V coagulation mutations and activated protein C resistance (RaPC) are alterations related with vein and artery thrombosis. In this study we aimed to determine whether RaPC is associated with the presence of Leiden and Cambridge mutation and the frequency of these mutations in the racially mestizo Mexican population. METHODS: We included 150 Mexican patients with primary thrombophilia and 100 healthy subjects in this study. RaPC was determined using commercial methods and genotypes FV Leiden and FV Cambridge with PCR-RFLPs. RESULTS: RaPC was positive in four patients and in one control individual; however, there was no presence of Leiden or Cambridge mutation in the studied group; thus, RaPC was not correlated with the presence of any of the studied mutations. CONCLUSIONS: These results indicate that there are other primary or secondary causes different from those studied, which condition the presence of RaPC. Furthermore, the frequency obtained for RaPC in our thrombophilic population of racially mixed Mexicans is lower compared to that obtained in the Caucasian population, most probably because they are genetically different populations.

La electroforesis capilar como una nueva estrategia en la medicina y el diagnóstico clínico / Capillary electrophoresis, a new diagnostic tool

Capillary electrophoresis (CE) may replace many conventional clinical laboratory methods, such as electrophoresis, Southern blotting, sequencing and HPLC (High-performance liquid chromatography). It is an ideal technique due to analytical speed, the possibility of handling great amount of samples, its capacity to separate small molecules according to their size, charge, hydrophobic and stereo-specificity its good reproducibility the use of small amounts of sample and reagents, its low costs and easy handling. The diagnosis of hereditary diseases or the predisposition to polygenic diseases related to specific mutations or polymorphisms can be carried out with this method. In clinical laboratories, this technique is being used for the analysis of several substrates present in urine or serum and for the diagnosis of some infectious agents. It is also a firsthand tool in forensic medicine for human identification and anthropology.