RESUMEN

Renal cystic diseases are common conditions whose etiology can be highly heterogeneous. They require a correct approach for adequate diagnosis and management. We aimed to illustrate part of the spectrum of renal cystic diseases through some clinical cases managed in our service. We describe 11 clinical cases including clinical entities such as renal multicystic dysplasia, and autosomal dominant and autosomal recessive polycystic renal disease, among other pathologies. Renal cystic diseases are heterogeneous in their clinical presentation, natural history, radiological findings, and genetic and pathophysiological basis. An integral clinical approach is needed to get a clear etiological diagnosis and offer adequate individualized care and follow-up for patients.

---

Las enfermedades quísticas renales son condiciones frecuentes cuya etiología puede ser muy heterogénea, por lo que se requiere un adecuado abordaje para su diagnóstico y manejo. El objetivo de este trabajo fue ilustrar parte del espectro de la enfermedad renal quística por medio de casos clínicos manejados en la Fundación Valle del Lili. Se describen 11 casos clínicos que incluyen enfermedades como displasia multiquística renal, enfermedad poliquística renal autosómica dominante y autosómica recesiva, entre otras. Las enfermedades quísticas renales varían en su presentación clínica, historia natural, hallazgos imagenológicos, bases genéticas y fisiopatológicas, por consiguiente, el enfoque diagnóstico y el manejo integral se debe realizar de forma individualizada y con un abordaje multidisciplinario.

Asunto(s)

Enfermedades Renales Quísticas , Humanos , Niño , Masculino , Enfermedades Renales Quísticas/genética , Enfermedades Renales Quísticas/diagnóstico por imagen , Femenino , Preescolar , Lactante , Adolescente , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Recesivo/genética , Riñón Poliquístico Autosómico Recesivo/diagnóstico por imagen , Riñón Displástico Multiquístico/genética , Riñón Displástico Multiquístico/diagnóstico por imagen

RESUMEN

Las enfermedades quísticas renales son condiciones frecuentes cuya etiología puede ser muy heterogénea, por lo que se requiere un adecuado abordaje para su diagnóstico y manejo. El objetivo de este trabajo fue ilustrar parte del espectro de la enfermedad renal quística por medio de casos clínicos manejados en la Fundación Valle del Lili. Se describen 11 casos clínicos que incluyen enfermedades como displasia multiquística renal, enfermedad poliquística renal autosómica dominante y autosómica recesiva, entre otras. Las enfermedades quísticas renales varían en su presentación clínica, historia natural, hallazgos imagenológicos, bases genéticas y fisiopatológicas, por consiguiente, el enfoque diagnóstico y el manejo integral se debe realizar de forma individualizada y con un abordaje multidisciplinario.

---

Renal cystic diseases are common conditions whose etiology can be highly heterogeneous. They require a correct approach for adequate diagnosis and management. We aimed to illustrate part of the spectrum of renal cystic diseases through some clinical cases managed in our service. We describe 11 clinical cases including clinical entities such as renal multicystic dysplasia, and autosomal dominant and autosomal recessive polycystic renal disease, among other pathologies. Renal cystic diseases are heterogeneous in their clinical presentation, natural history, radiological findings, and genetic and pathophysiological basis. An integral clinical approach is needed to get a clear etiological diagnosis and offer adequate individualized care and follow-up for patients.

Asunto(s)

Humanos , Pediatría , Radiología , Genética , Enfermedades Renales Poliquísticas , Diagnóstico por Imagen , Riñón Poliquístico Autosómico Recesivo , Riñón Poliquístico Autosómico Dominante

RESUMEN

INTRODUCTION: CAD (MIM*114010) encodes a large multifunctional protein with the enzymatic activity of the first three enzymes initiating and controlling the de novo pyrimidine biosynthesis pathway. Biallelic pathogenic variants in CAD cause the autosomal recessive developmental and epileptic encephalopathy 50 (MIM #616457) or CAD deficiency presenting with epilepsy, status epilepticus (SE), neurological deterioration and anemia with anisopoikilocytosis. Mortality is around 9% of patients, mainly related to the no use of its specific treatment with uridine. Majority of reported cases have an early onset during infancy, with some few starting later in childhood. CASE REPORT: Here we report a deceased female patient with CAD deficiency whose epilepsy started at 14 years. She showed a rapid neurologic deterioration including cognitive decline, electroencephalographic background slowing which later evolved to a fatal refractory SE and supra and infratentorial atrophy on neuroimaging. Anemia developed after SE onset. METHODS AND RESULTS: her post-mortem whole exome sequencing identified biallelic missense variants in CAD (NM_004341.5): c.[2944G > A];[5366G > A] p.[(Asp982Asn)];[(Arg1789Gln)]. Our review of twenty-eight reported cases (2015-2023) revealed an epilepsy age onset from neonatal period to 7 years and the SE prevalence of 46 %. DISCUSSION: With our case, we highlight the relevance of suspecting this treatable condition in older patients and in SE with no evident etiology.

Asunto(s)

Epilepsia , Humanos , Femenino , Epilepsia/genética , Adolescente , Dihidroorotasa/genética , Mutación Missense , Estado Epiléptico/genética , Disfunción Cognitiva/genética , Edad de Inicio , Aspartato Carbamoiltransferasa , Carbamoil-Fosfato Sintasa (Glutamina-Hidrolizante)

RESUMEN

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.

Asunto(s)

Disgerminoma , Linaje , Adolescente , Adulto , Femenino , Humanos , Adulto Joven , Disgerminoma/genética , Disgerminoma/patología , Disgenesia Gonadal/genética , Mutación Missense , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología

RESUMEN

Autosomal recessive congenital ichthyoses (ARCI) are a skin pathology due to genetic causes characterized by a variable degree of desquamation, accompanied by erythema. The degree of symptoms is variable, different altered genes are involved, and the symptoms drastically affect patients' quality of life. Topical treatments are a first-choice strategy due to their ease of application and cost; however, enteral administration of retinoids offers greater efficacy, although with certain limitations. Despite the treatment alternatives, ARCI will persist throughout life, disabling people. Therefore, the search for new treatments always remains necessary. Especially repositioning drugs could be a short-term alternative to new affordable treatments for patients. Taking advantage of extensive knowledge of known drugs or biologics could ensure more accessible and possibly lower-cost treatments. This review briefly and concisely addresses possible repositioning strategies with drugs and biologics for ichthyosis.

RESUMEN

Trisomy X is the most frequent sex chromosome anomaly in women, but it is often underdiagnosed postnatally because most patients do not show any clinical manifestation. It is estimated that only 10% of patients with trisomy X are diagnosed by clinical findings. Thus, it has been proposed that the clinical spectrum is not yet fully delimited, and additional uncommon or atypical clinical manifestations could be related to this entity. The present report describes a female carrying trisomy X but presenting atypical manifestations, including severe intellectual disability, short stature, thymus hypoplasia, and congenital hypothyroidism (CH). These clinical findings were initially attributed to trisomy X. However, chromosome microarray analysis (CMA) subsequently revealed that the patient also bears a heterozygous 304-kb deletion at 16p11.2. This pathogenic copy-number variant (CNV) encompasses 13 genes, including TUFM. Some authors recommend that when a phenotype differs from that described for an identified microdeletion, the presence of pathogenic variants in the non-deleted allele should be considered to assess for an autosomal recessive disorder; thus, we used a panel of 697 genes to rule out a pathogenic variant in the non-deleted TUFM allele. We discuss the possible phenotypic modifications that might be related to an additional CNV in individuals with sex chromosome aneuploidy (SCA), as seen in our patient. The presence of karyotype-demonstrated trisomy X and CMA-identified 16p11.2 deletion highlights the importance of always correlating a patient's clinical phenotype with the results of genetic studies. When the phenotype includes unusual manifestations and/or exhibits discrepancies with that described in the literature, as exemplified by our patient, a more extensive analysis should be undertaken to enable a correct diagnosis that will support proper management, genetic counseling, and medical follow-up.

Asunto(s)

Aberraciones Cromosómicas Sexuales , Trisomía , Humanos , Femenino , Trisomía/diagnóstico , Trisomía/genética , Deleción Cromosómica , Fenotipo , Cariotipo

RESUMEN

Couple screening aims to identify couples with an increased risk of having a child affected with an autosomal recessive or X-linked disorder, in order to facilitate informed reproductive decision making. Both expectant parents should be screened as a single entity, instead of individual testing. Carrier testing was typically performed for a few relatively common recessive disorders associated with significant morbidity, reduced life expectancy and often because of a considerably higher carrier frequency in a specific population for certain diseases. However, new genetic testing technologies enable the expansion of screening to multiple conditions, genes and sequence variants. There are multiple reproductive options for screening couples at risk, particularly when genetic traits are detected in the preconception period.

Asunto(s)

Detección Precoz del Cáncer , Pruebas Genéticas , Niño , Humanos , Padres , Asesoramiento Genético

RESUMEN

Introducción: Las ictiosis hereditarias pueden ser sindrómicas y no sindrómicas, estas últimas, de acuerdo con la expresión fenotípica cutánea, incluyen, ictiosis comunes, ictiosis recesiva ligada al cromosoma X, ictiosis congénita autosómica recesiva, ictiosis queratinopática y otras formas. La ictiosis congénita autosómica recesiva, incluye tres fenotipos principales: La ictiosis arlequín, ictiosis laminar y eritrodermia ictiosiforme congénita. Comunicamos un caso clínico de ictiosis laminar recurrente en una familia. Reporte de caso: Recién nacido pretérmino, tiene hermana de 6 años, con diagnóstico de ictiosis lamelar. Madre niega consanguinidad con esposo, y parientes con esta enfermedad. Al nacer se observa cubierto de membrana colodión en toda la piel, ectropión y eclabio. El manejo inicial, fue gasa vaselinada, lagrimas artificiales, gasas húmedas en los ojos. Actualmente baños con crema de ducha, Shampoo y Aceite mineral, cremas y loción hidratantes y Acitretina, está en franca mejoría. Conclusiones: Con la historia clínica y los antecedentes familiares es posible diagnosticar ictiosis laminar. El manejo es multidisciplinario.

---

Introduction: Hereditary ichthyosis can be syndromic and non-syndromic, the latter, according to the cutaneous phenotypic expression, include common ichthyosis, X-linked recessive ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis and other forms. Autosomal recessive congenital ichthyosis includes three main phenotypes: harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma. We report a clinical case of recurrent lamellar ichthyosis in a family. Case Report: Preterm newborn, has a 6-year-old sister, diagnosed with lamellar ichthyosis. Mother denies consanguinity with husband, and relatives with this disease. At birth, it is observed covered with collodion membrane throughout the skin, ectropion and eclabio. The initial management was Vaseline gauze, artificial tears, wet gauze in the eyes. Currently baths with shower cream, Shampoo and mineral oil, moisturizing creams and lotions and Acitretin, is clearly improving. Conclusions: With the medical history and family history it is possible to diagnose lamellar ichthyosis. Management is multidisciplinary.

RESUMEN

Osteogenesis imperfecta (OI) is a rare low-bone mass skeletal Mendelian disorder characterized by bone fragility leading to bone fractures, with deformities and stunted growth in the more severe phenotypes. Other common, nonskeletal findings include blue sclerae and dentinogenesis imperfecta. It is caused mainly by quantitative or structural defects in type I collagen, although dysregulation of different signaling pathways that play a role in bone morphogenesis has been described to be associated with a small fraction of individuals with OI. Recently, a homozygous variant in the translation start site of CCDC134, showing increased activation of the RAS/MAPK signaling pathway, has been reported in three families of Moroccan origin with a severe, deforming form of OI. We report on a 9-year-old Brazilian boy, harboring the same homozygous variant in CCDC134, also presenting severe bone involvement. This report contributes to the phenotypic delineation of this novel autosomal recessive form of OI, which presents with high prevalence of nonunion fractures considered rare events in OI in general. In addition, it expands the phenotype to include base skull anomalies, potentially leading to serious complications, as seen in severe forms of OI. A poor response to bisphosphonate therapy was observed in these individuals. As the variant in CCDC134 leads to dysregulation of the RAS/MAPK signaling pathway, drugs targeted to this pathway could be an alternative to achieve a better management of these individuals.

Asunto(s)

Fracturas Óseas , Osteogénesis Imperfecta , Huesos , Colágeno Tipo I/genética , Fracturas Óseas/complicaciones , Homocigoto , Humanos , Proteínas de la Membrana/genética , Osteogénesis Imperfecta/complicaciones , Fenotipo

RESUMEN

OBJECTIVE: This study aimed to evaluate liver malformations and intrahepatic bile ductal ectasia and dilatation (IBDED) in cases of prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD) using magnetic resonance imaging (MRI). METHODS: This retrospective study involved 209 cases referred for fetal MRI studies (f-MRI) from March 2004 and December 2019, suspicious of congenital renal disease. Fetuses that met the criteria for ARPKD were selected. RESULTS: Six cases were diagnosed as ARPKD (2.8%). The median gestational age at MRI examination was 28 weeks (24-36 weeks). IBDED was observed in 84% of cases. Moreover, 66% presented multilobar liver lesions, and 33% exhibited monolobar lesions. The "central dot sign" (CDS) was found in half of the cases. CONCLUSION: In this case series of prenatal diagnosis of ARPKD using f-MRI, IBDED was present in the majority of the cases, and the CDS was noted in half of the cases.

Asunto(s)

Riñón Poliquístico Autosómico Recesivo , Bilis , Dilatación Patológica/diagnóstico por imagen , Femenino , Feto/patología , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Riñón Poliquístico Autosómico Recesivo/complicaciones , Riñón Poliquístico Autosómico Recesivo/diagnóstico por imagen , Embarazo , Estudios Retrospectivos

RESUMEN

BACKGROUND: Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities' current methodology for screening, which focuses on the detecting multiple genetic disorders at once. Here, we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects (PGT-M) approach for detecting propionic acidemia (PA) in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit (PCCA) couple. CASE SUMMARY: A fertile 32-years old Mexican couple with denied consanguinity sought antenatal genetic counseling. They were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit (PCCB) genotype. Next-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant (c.2041-1G>T, ClinVar:RCV000802701.1; dbSNP:rs1367867218) in both parents. The couple requested in vitro fertilization (IVF) and PGT-M for PA. From IVF, 12 oocytes were collected and fertilized, of which two resulted in high-quality embryos. Trophectoderm biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were euploid. End-point polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female embryo. Both embryos were transferred, resulting in a clinical pregnancy and the delivery of a healthy male newborn (38 wk, weight: 4080 g, length: 49 cm, APGAR 9/9). The absence of PA was confirmed by expanded newborn screening. CONCLUSION: We show that using PGT-M with Whole Genome Amplification templates, coupled with IVF, can reduce the transmission of a pathogenic variant of the PCCA gene.

RESUMEN

Congenital disorders of glycosylation (CDG) are a heterogeneous group of genetic defects in glycoprotein and glycolipid glycan synthesis and attachment. A CDG subgroup are defects in the conserved oligomeric Golgi complex encoded by eight genes, COG1-COG8. Pathogenic variants in all genes except the COG3 gene have been reported. COG1-CDG has been reported in five patients. We report a male with neonatal seizures, dysmorphism, hepatitis and a type 2 serum transferrin isoelectrofocusing. Exome sequencing identified a homozygous COG1 variant (NM_018714.3: c.2665dup: p.[Arg889Profs*12]), which has been reported previously in one patient. We review the reported patients.

Asunto(s)

Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/fisiopatología , Proteínas Adaptadoras del Transporte Vesicular/genética , Trastornos Congénitos de Glicosilación/patología , Mutación del Sistema de Lectura , Glicosilación , Humanos , Recién Nacido , Masculino , Secuenciación del Exoma

RESUMEN

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) causes unique retinal abnormalities, which have not been systematically investigated. OBJECTIVE: To deeply phenotype the retina in ARSACS in order to better understand its pathogenesis and identify potential biomarkers. METHODS: We evaluated 29 patients with ARSACS, 66 with spinocerebellar ataxia (SCA), 38 with autosomal recessive cerebellar ataxia (ATX), 22 with hereditary spastic paraplegia (SPG), 21 cases of papilledema, and 20 healthy controls (total n = 196 subjects). Participants underwent visual acuity assessment, intraocular pressure measurement, fundoscopy, and macular and peripapillary optical coherence tomography (OCT). Macular layers thicknesses in ARSACS were compared with those of age-matched healthy controls. Ophthalmologists analyzed the scans for abnormal signs in the different patient groups. Linear regression analysis was conducted to look for associations between retinal changes and age, age at onset, disease duration, and Scale for the Assessment and Rating of Ataxia (SARA) scores in ARSACS. RESULTS: Only patients with ARSACS exhibited peripapillary retinal striations (82%) on fundoscopy, and their OCT scans revealed foveal hypoplasia (100%), sawtooth appearance (89%), papillomacular fold (86%), and macular microcysts (18%). Average peripapillary retinal nerve fiber layer (pRNFL) was thicker in ARSACS than in SCA, ATX, SPG, and controls; a cut-off of 121 µm was 100% accurate in diagnosing ARSACS. All macular layers were thicker in ARSACS when compared to healthy controls. RNFL thickness in the inferior sector of the macula positively correlated with SARA scores. CONCLUSIONS: Retinal abnormalities are highly specific for ARSACS, and suggest retinal hyperplasia due to abnormal retinal development. OCT may provide potential biomarkers for future clinical trials. © 2021 International Parkinson and Movement Disorder Society.

Asunto(s)

Espasticidad Muscular , Ataxias Espinocerebelosas , Biomarcadores , Humanos , Espasticidad Muscular/diagnóstico por imagen , Retina/diagnóstico por imagen , Ataxias Espinocerebelosas/congénito , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genética

Asunto(s)

Ataxia Cerebelosa , Trastornos del Movimiento , Ataxia Cerebelosa/genética , Genes Recesivos , Humanos , alfa-Fetoproteínas

RESUMEN

Autosomal recessive cerebellar ataxia type 1 (ARCA-1) or spinocerebellar ataxia autosomal recessive type 8 (SCAR8) is a slowly progressive neurodegenerative disorder that occurs due to mutations in the spectrin repeat containing nuclear envelope protein 1 (SYNE1) gene. Previously considered a rare cause of ARCA, related to French-Canadian patients from Beauce, Quebec, Canada, SYNE1 ataxia is now known to be of worldwide distribution. We present the case report of a 54-year-old male patient with the genetic diagnosis of SYNE1 ataxia, presenting with a SYNE1 gene mutation never described in Chilean population before.

Asunto(s)

Ataxia Cerebelosa , Canadá , Ataxia Cerebelosa/diagnóstico por imagen , Ataxia Cerebelosa/genética , Proteínas del Citoesqueleto/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética

RESUMEN

BACKGROUND: Acid sphingomyelinase deficiency (ASMD) is a rare group of autosomal recessive disorders. This report provides the first detailed description of the periodontal condition and treatment response in a patient with chronic visceral ASMD. CASE DESCRIPTION: A 49-year-old white woman with ASMD showed elevated visible plaque index (VPI), gingival bleeding index (GBI), and bleeding on probing (BOP) at 100% of sites. Periodontal pocket depths (PPD) were mostly shallow to moderate (at 96% of sites), whereas the loss of clinical attachment (CAL) was moderate to severe (54% and 46% of sites, respectively, at 4-6 mm and ≥7 mm categories). Periapical radiographs revealed the presence of furcation involvement and intra-bony defects. The periodontal diagnosis was periodontitis stage IV, generalized, grade C. Ninety days after the end of the supra and subgingival control (e.g., cause-related therapy), marked reduction was observed for all periodontal indicators: VPI (-83%), GBI (-79%), BOP (-85%), elimination of sites PPD ≥7 mm, 27% increase in sites PPD 1-3 mm (from 64% to 91%), and gain of clinical attachment (gain of 11% CAL 1-3 mm and 25% CAL 4-6 mm; and a reduction of 36% CAL ≥7 mm). PRACTICAL IMPLICATIONS: Despite the severity of the initial periodontal condition, the patient with chronic visceral ASMD responded well to the non-surgical periodontal treatment.

Asunto(s)

Enfermedades de las Encías , Enfermedad de Niemann-Pick Tipo A , Periodontitis , Índice de Placa Dental , Raspado Dental , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pérdida de la Inserción Periodontal , Bolsa Periodontal

RESUMEN

Basel-Vanagaite-Smirin-Yosef syndrome is a recently described autosomal recessive intellectual disability syndrome caused by variants in the MED25 gene. While it was originally identified in Brazil, it was further described in Israel by authors who are now the namesake of the condition. A 2018 publication further contributed to its delineation, but the patient's phenotype was complicated by a dual diagnosis. More recently, an article describing a set of affected siblings was published. We describe three, previously unreported, patients showing clinical variability for this newly defined syndrome. The major features determined by "reverse phenotyping" include significant to profound developmental delays/intellectual disability with absent or delayed speech, epilepsy, ocular abnormalities, cleft lip and/or palate, congenital heart disease, urogenital anomalies, skeletal abnormalities, brain malformations and/or microcephaly, failure to thrive, and dysmorphic features. The authors suggest the delineation of an acronym using the gene name and common features seen across the majority of patients reported so far. This new nomination, MED-DOCS, may help clinicians to recognize, suspect, and remember this novel syndrome.

Asunto(s)

Anomalías Múltiples/genética , Predisposición Genética a la Enfermedad , Discapacidad Intelectual/genética , Complejo Mediador/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/fisiopatología , Brasil/epidemiología , Preescolar , Labio Leporino/genética , Labio Leporino/fisiopatología , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/fisiopatología , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/fisiopatología , Israel/epidemiología , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Microcefalia/fisiopatología , Fenotipo , Polimorfismo de Nucleótido Simple/genética

RESUMEN

Resumen Las ictiosis congénitas autosómicas recesivas (ICAR) son poco frecuentes a nivel mundial con una incidencia de 1:300,000 nacimientos, se caracterizan por trastornos de la queratinización, entre sus variantes engloban las formas no sindrómicas de ictiosis, como la ictiosis laminar (IL), la eritrodermiaictiosiforme congénita (EIC) y actualmente se incluyen la ictiosis arlequín, el bebé colodión autorresolutivo, el bebé colodión autorresolutivoacral y la ictiosis en traje de baño. Desde el punto de vista genético son heterogéneas, originadas por una mutación en el gen de la transglutaminasa 1 y se las haasociado a TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 y ABCA12. Clínicamente, la ictiosis se caracteriza principalmente por piel gruesa, escamas laminares adherentes con hendiduras profundas. En este trabajo pretende revisar los conocimientos actuales en el campo de las ICAR, incluyendo aspectos clínicos, histológicos, ultraestructurales, genético-moleculares, tratamiento,y también su manejo clínico.

---

Abstract The autosomal recessive congenital ichthyosis (ARCI) is a rare worldwide condition with an incidence of (1: 300,000 births), characterized by disorders of keratinization, among its variants encompass the non-syndromic forms of ichthyosis, such as laminar ichthyosis (IL) , congenital ichthyosiform erythroderma (EIC) and currently include harlequin ichthyosis, self-healing colodion baby, acral self-healing colodion baby and ichthyosis in swimsuits. From a genetic point of view, they're heterogeneous, originated by a mutation in the gene of transglutaminase 1 and associated with TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 and ABCA12. Clinically, ichthyosis is mainly characterized by thick skin, adherent lamellar scales with deep clefts. The aim of this work is to review the current knowledge in the field of ICAR, including clinical, histological, ultrastructural, genetic-molecular and therapeutic aspects as well as its clinical management.

Asunto(s)

Humanos , Femenino , Preescolar , Transglutaminasas/biosíntesis , Ictiosis Lamelar/patología , Ictiosis Lamelar/tratamiento farmacológico , Ictiosis/epidemiología , Ictiosis Lamelar/diagnóstico

RESUMEN

The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are available. The study aims to assess the prevalence, distribution, and neurological features of the Cuban population with hereditary ataxias. A nationwide epidemiological study of hereditary ataxias was conducted in Cuba between March 2017 and June 2018. Patients were scheduled at the Cuban ataxia research center, various hospitals, or at their homes. Demographic and clinical variables were obtained through standardized questionnaires and validated clinical tools. Overall, 1001 patients were diagnosed with hereditary ataxias for a nationwide prevalence of 8.91 cases/100.000 inhabitants. Spinocerebellar ataxia type 2 (SCA2) was the commonest subtype, with highest prevalences at Holguín province (47.86/100.000), and a broad dissemination in the whole country. Most of neurological features were common between all SCA cohorts, but the frequencies of some of them varied between distinct subtypes. Within the SCA2 cohort, significant influences of long mutation size and higher disease duration over the muscle atrophy and oculomotor disorders were observed. Besides, higher disease durations were associated with resting tremor and dysphagia, whereas shorter disease durations were associated with hyperreflexia. The spreading of SCA2 to whole country and the documented raising of its prevalence set the rationales for higher-scope medical care and research strategies, supported in collaborative research networks. The wide epidemiological, clinical, and genetic characterization of this founder SCA2 population identifies this homogeneous cohort as an attractive source for the development of future clinical-genetic and therapeutic researches.

Asunto(s)

Degeneraciones Espinocerebelosas/epidemiología , Cuba/epidemiología , Humanos , Prevalencia , Degeneraciones Espinocerebelosas/genética