RESUMEN
BACKGROUND: Non-photosensitive trichothiodystrophies (TTDs) are a diverse group of genodermatoses within the subset of conditions known as "sulphur-deficient brittle hair" syndromes. A part of them has only recently been identified, revealing novel causative genes and very rare phenotypes of these genetic skin disorders. At the same time, the molecular basis of previously published and unresolved cases has been revealed through the introduction of innovative genetic techniques. We have previously described the facial phenotype of patients with the Photosensitive form of TTD during childhood. This study marks the beginning of an effort to expand the analysis to include individuals of the same age who do not have photosensitivity. METHODS: A total of 26 facial portraits of TTD paediatric patients with Non-photosensitivity from the literature were analysed using computer-aided technologies, and their facial features were examined through a detailed clinical review. RESULTS: Distinct facial features were identified in both Photosensitive and Non-photosensitive TTDs. CONCLUSION: The present study has comprehensively elucidated the facial features in TTDs, encompassing the Non-photosensitive clinical spectrum.
Asunto(s)
Fenotipo , Síndromes de Tricotiodistrofia , Humanos , Síndromes de Tricotiodistrofia/genética , Síndromes de Tricotiodistrofia/patología , Niño , Masculino , Femenino , Preescolar , Adolescente , Cara/anomalías , Cara/patología , LactanteRESUMEN
Among genodermatoses, trichothiodystrophies (TTDs) are a rare genetically heterogeneous group of syndromic conditions, presenting with skin, hair, and nail abnormalities. An extra-cutaneous involvement (craniofacial district and neurodevelopment) can be also a part of the clinical picture. The presence of photosensitivity describes three forms of TTDs: MIM#601675 (TTD1), MIM#616390 (TTD2) and MIM#616395 (TTD3), that are caused by variants afflicting some components of the DNA Nucleotide Excision Repair (NER) complex and with more marked clinical consequences. In the present research, 24 frontal images of paediatric patients with photosensitive TTDs suitable for facial analysis through the next-generation phenotyping (NGP) technology were obtained from the medical literature. The pictures were compared to age and sex-matched to unaffected controls using 2 distinct deep-learning algorithms: DeepGestalt and GestaltMatcher (Face2Gene, FDNA Inc., USA). To give further support to the observed results, a careful clinical revision was undertaken for each facial feature in paediatric patients with TTD1 or TTD2 or TTD3. Interestingly, a distinctive facial phenotype emerged by the NGP analysis delineating a specific craniofacial dysmorphic spectrum. In addition, we tabulated every single detail within the observed cohort. The novelty of the present research includes the facial characterization in children with the photosensitive types of TTDs through the 2 different algorithms. This result can become additional criteria for early diagnosis, and for subsequent targeted molecular investigations as well as a possible tailored multidisciplinary personalized management.
Asunto(s)
Trastornos por Fotosensibilidad , Síndromes de Tricotiodistrofia , Humanos , Síndromes de Tricotiodistrofia/diagnóstico , Síndromes de Tricotiodistrofia/genética , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/genética , Cara , Cabello , Fenotipo , Reparación del ADNRESUMEN
In 2018, a new clinical subtype, caused by biallelic variants in the AEBP1 gene, encoding the ACLP protein, was added to the current nosological classification of the Ehlers-Danlos Syndromes (EDS). This new phenotype, provisionally termed EDS classical-like type 2 (clEDS2), has not yet been fully characterized, as only nine cases have been reported to date. Here we describe a patient, homozygous for a novel AEBP1 pathogenic variant (NM_001129.5 c.2123_2124delTG (p.Val708AlafsTer5)), whose phenotype is reminiscent of classical EDS but also includes previously unreported multiple congenital malformations. Furthermore, we briefly summarize the current principal clinical manifestations of clEDS2 and the molecular evidence surrounding the role of AEBP1 in the context of extracellular matrix homeostasis and connective tissue development. Although a different coexisting etiology for the multiple congenital malformations of our patient cannot be formally excluded, the emerging role of ACLP in TGF-ß and WNT pathways may explain their occurrence and the phenotypical variability of clEDS2.
Asunto(s)
Síndrome de Ehlers-Danlos , Humanos , Mutación , Síndrome de Ehlers-Danlos/patología , Matriz Extracelular/genética , Fenotipo , Homocigoto , Carboxipeptidasas/genética , Proteínas Represoras/genéticaRESUMEN
X-linked intellectual disability can be diagnosed in about 10-12% of intellectually disabled males. In the past, mutations affecting the PAK3 gene (p21 protein-activated kinase 3, MIM#300142) have been associated with a non-syndromic form of X-linked intellectual disability, which has to date been identified in a limited number of families.Since this neurodevelopmental disorder mostly afflicts males, descriptions of symptomatic female carriers are quite rare.We describe a female patient with neurodevelopmental delay and a novel PAK3 variant. Interestingly, she manifests craniofacial anomalies, including microcephaly, representing the second reported microcephalic female but the first for whom a detailed clinical description is available. She also displays other uncommon clinical findings, which we illustrate.Moreover, a comprehensive clinical and molecular review of all to date published patients has been made. This study contributes to further delineate the PAK3-related phenotype, which can be considered a non-syndromic X-linked intellectual disability, with seemingly recurrent craniofacial abnormalities.
Asunto(s)
Discapacidades del Desarrollo/genética , Discapacidad Intelectual/genética , Microcefalia/genética , Fenotipo , Quinasas p21 Activadas/genética , Preescolar , Discapacidades del Desarrollo/patología , Femenino , Humanos , Discapacidad Intelectual/patología , Microcefalia/patología , Mutación , Quinasas p21 Activadas/metabolismoRESUMEN
Koolen-de Vries syndrome (KdVS, MIM#610443) is a rare malformation condition mainly characterized by cognitive impairment in association with craniofacial and visceral anomalies. The core phenotype is caused by mutations in the chromatin remodeler KANSL1 (MSL1V1, KIAA1267, KAT8 Regulatory NSL Complex Subunit 1, MIM#612452), which maps to 17q21.31 critical genomic region (Koolen et al., Nature Genetics 2012;44:639-641). Considering its molecular basis, KdVS is included in the group of Developmental Disorders of Chromatin Remodeling (DDCRs), also termed chromatinopathies. We describe the first KdVS patient of Southern India ethnicity, harboring the typical de novo 17q21.31 microdeletion, including KANSL1. Observed facial features and congenital anomalies are in line with the already reported KdVS phenotype, suggesting that phenotypic features are consistent across different ethnicities.
Asunto(s)
Anomalías Múltiples/etnología , Discapacidad Intelectual/etnología , Proteínas Nucleares/genética , Anomalías Múltiples/genética , Adulto , Envejecimiento , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 17/ultraestructura , Etnicidad/genética , Cara/anomalías , Femenino , Defectos del Tabique Interatrial/genética , Defectos del Tabique Interatrial/cirugía , Humanos , India , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/genética , Discapacidad Intelectual/genética , Maloclusión de Angle Clase III/genética , Fenotipo , Eliminación de SecuenciaRESUMEN
Functional tricuspid regurgitation (FTR) is the most frequent etiology of tricuspid valve pathology in Western countries. In the last years, many investigators have reported evidence in favor of a more aggressive surgical approach to FTR and interest has been growing in the physiopathology and treatment of FTR. The purpose of this editorial is to explore the anatomical basis, pathophysiology, therapeutic approaches and the perspectives of treatment.