RESUMEN
Oral-facial-digital syndrome (OFDS) is a multisystemic ciliopathic disorder with an autosomal recessive mode of inheritance. OFDS usually manifests with typical craniofacial anomalies and variable occurrence of polydactyly. Germline variants in CPLANE1 cause OFDS VI. In this study, we investigated a 26-year-old Chinese female patient who was 23+1 weeks pregnant. She had a history of adverse pregnancy outcomes with multiple foetal malformations. We performed ultrasonography and identified the foetus as having a posterior fossa Blake cyst and postaxial polydactyly. The patient decided to terminate her pregnancy, and further genetic molecular analysis was performed. We identified the aborted foetus as having postaxial polydactyly. Whole-exome sequencing identified a missense variant (c.3599C>T, p.A1200V) in exon 20 and a c.834+1G>T variant in exon 7 of CPLANE1 (NM_023073.3) in the foetus. Sanger sequencing confirmed that these variants came from the parents of the foetus. In this study, we investigated a family with OFDS VI through genetic testing and bioinformatics analysis, which provided powerful help for prenatal diagnosis. Then, we demonstrated that the cell migration rate and the number of cilia were decreased after interference with CPLANE1 expression in NIH/3T3 cells. After CPLANE1 knockdown, the Hh signalling pathway was inhibited, and the Hh pathway activator SAG reversed the inhibitory effect. This is the first report of a family with OFDS VI in the Chinese population.
Asunto(s)
Anomalías Múltiples , Síndromes Orofaciodigitales , Polidactilia , Anomalías Múltiples/genética , Adulto , Animales , Cilios/genética , Femenino , Dedos/anomalías , Humanos , Ratones , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Embarazo , Dedos del Pie/anomalías , Secuenciación del ExomaRESUMEN
Oral-facial-digital syndromes (OFDSs) as a subgroup of ciliopathies are rare genetic disorders characterized by the association of abnormalities of the face, oral cavity, and extremities. OFDS XVII is a recently described subtype of OFDS that presents with developmental delay, facial dysmorphism, high palate, tongue nodules, brain malformations, cardiac anomaly, polydactyly, renal malformation, and various other findings. OFDS XVII is caused by biallelic variants in INTU gene and is inherited autosomal recessively. Intu is part of the CPLANE protein module that has an essential role in the ciliary transport system and function. INTU pathogenic variants have been reported in two patients with OFDS XVII, in two patients with short-rib thoracic dysplasia-20 with polydactyly (SRTD20), and one with nephronophthisis so far. We report the third family in the literature with OFDS XVII, with urogenital malformations as an additional finding.
Asunto(s)
Síndromes Orofaciodigitales , Enfermedades Renales Poliquísticas , Polidactilia , Cara/anomalías , Humanos , Síndromes Orofaciodigitales/complicaciones , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Polidactilia/complicaciones , ProteínasRESUMEN
Orofaciodigital syndrome type 1 (OFDS1) is a genetic disorder characterized by specific oral, facial, and limb malformations. A 14-month-old girl with congenital cleft palate, lower lip midline cleft, and digital anomalies admitted to our hospital was preliminarily diagnosed with OFDS1. Genetic analysis revealed that she carried a heterozygous variant of OFD1 at locus Xp22.2 on the X chromosome. Herein, we present the specific phenotype and genotype and the treatment modalities for this patient and references for diagnosing and treating OFDS.
Asunto(s)
Fisura del Paladar , Deformidades Congénitas de las Extremidades , Síndromes Orofaciodigitales , Femenino , Humanos , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Exones , Cara , Fisura del Paladar/diagnóstico , Fisura del Paladar/genética , Fisura del Paladar/cirugíaRESUMEN
Oral-facial-digital syndromes (OFDS) are a heterogeneous and rare group of Mendelian disorders characterized by developmental abnormalities of the oral cavity, face, and digits caused by dysfunction of the primary cilium, a mechanosensory organelle that exists atop most cell types that facilitates organ patterning and growth. OFDS is inherited both in an X-linked dominant, X-linked recessive, and autosomal recessive manner. Importantly, though many of the causal genes for OFDS have been identified, up to 40% of OFD syndromes are of unknown genetic basis. Here we describe three children with classical presentations of OFDS including lingual hamartomas, polydactyly, and characteristic facial features found by exome sequencing to harbor variants in causal genes not previously associated with OFDS. We describe a female with hypothalamic hamartoma, urogenital sinus, polysyndactyly, and multiple lingual hamartomas consistent with OFDVI with biallelic pathogenic variants in CEP164, a gene associated with ciliopathy-spectrum disease, but never before with OFDS. We additionally describe two unrelated probands with postaxial polydactyly, multiple lingual hamartomas, and dysmorphic features both found to be homozygous for an identical TOPORS missense variant, c.29 C>A; (p.Pro10Gln). Heterozygous TOPORS pathogenic gene variants are associated with autosomal dominant retinitis pigmentosa, but never before with syndromic ciliopathy. Of note, both probands are of Dominican ancestry, suggesting a possible founder allele.
Asunto(s)
Alelos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Variación Genética , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Femenino , Pruebas Genéticas , Genotipo , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Mutación , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Fenotipo , Ubiquitina-Proteína Ligasas/genética , Secuenciación del ExomaRESUMEN
Orofaciodigital syndrome type I and X-linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first report of a newborn male with a novel hemizygous variant in OFD1 gene c.515T>C, (p.Leu172Pro) resulting in X-linked Joubert syndrome and orofaciodigital features with complete pituitary gland aplasia and subsequent severe hypoplasia of peripheral endocrine glands. This clinical report expands the phenotypic spectrum of endocrine system involvement in OFD1-related disorders and suggests that OFD1 gene may be related to pituitary gland development.
Asunto(s)
Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Cerebelo/anomalías , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Genes Ligados a X , Enfermedades Renales Quísticas/diagnóstico , Enfermedades Renales Quísticas/genética , Mutación , Fenotipo , Proteínas/genética , Retina/anomalías , Alelos , Genotipo , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Linaje , Hipófisis/anomalías , Radiografía , Secuenciación del ExomaAsunto(s)
Síndromes Orofaciodigitales , Enfermedades Renales Poliquísticas , Riñón Poliquístico Autosómico Dominante , Humanos , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/genética , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Enfermedades Renales Poliquísticas/diagnóstico , Enfermedades Renales Poliquísticas/genética , RiñónRESUMEN
Orofaciodigital syndrome (OFD) is a group of hereditary disorders identified by malformations of the mouth (oris), face (facies), hands and feet (digitus=finger and toe). Although there are several different types reported in the literature, there is a great overlap in their clinical presentation. The full spectrum of all disorders due to OFD is not yet fully understood, since each patient shows variations in the expression of the syndrome. In the oral cavity, teeth are often affected by various alterations, such as dental caries, abnormal teeth, enamel hypoplasia, supernumerary teeth and dental agenesis. Treatment of a syndromic patient with a complex picture showing conditions such as palatine fissures and a severe hypodontia involves a multidisciplinary approach and a careful periodical follow-up.
Asunto(s)
Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/terapia , Caries Dental , Hipoplasia del Esmalte Dental , Estudios de Seguimiento , Humanos , Diente SupernumerarioRESUMEN
The oral-facial-digital syndrome belongs to a group of hereditary diseases, manifested by multiple birth defects (usually, the face and fingers). At the current stage, there are 14 genetic variations of the oral-facial-digital syndrome. The presence of various abnormalities of the oral cavity, face and fingers is common for all of them, but each syndrome has a specific phenotype or type of inheritance. The etiology of this syndrome is unknown. It is inherited in an X-linked dominant pattern. Aim of the study: to describe and analyze the clinical case of oral-facial-digital syndrome. Data of the patient (Kira M., 11 months old): clinical-anamnestic examination, chest radiography, ultrasound investigation, molecular-genetic testing OFD1. Results Numerous miliae are detected on the face and ears of the child. Facial dysmorphy (large wide eyes, epicantus, wide nose bridge, telecantus, small mouth, small beak shaped nose, hypoplasia of the wings of the nose, small chin). The large fontanel is closed. Focal alopecia and dry hair are noted. Syndactyly of 2nd-3rd toes, asymmetrical shortening of the index finger of the right hand. Oral cavity examination reveals cleft palate, ankyloglossy and tongue lobulation. Transcranial ultrasonography: M echodex = 50.0 mm. M echosin = 52.0 mm. VIII = 6.9 mm (N up to 3.0 mm). V latdex = 24.4 mm, V latsin = 25.0 mm (N up to 16.0 mm). Neurologist's consultation: "Congenital brain malformation: agenesis of corpus callosum, congenital cerebral cysts." Ultrasound examination of the abdominal organs detected liver enlargement (anteroposterior size of the right lobe: 78 mm (N up to 65 mm), left lobe: 0.38 mm (+1.5 cm) Conclusion Oral-facial-digital syndrome type I is an inherited pathology, which in most cases is diagnosed immediately after birth on the basis of oral, facial and digital anomalies. Molecular genetic study makes it possible to confirm this disease and provide counseling to family members. Elimination of some developmental defects (hard palate plastic, correction of frenulum hyperthrophy), as well as a properly selected complex of therapeutic and rehabilitation measures greatly improves the quality of life of the patient and contributes to a favorable forecast.
Asunto(s)
Síndromes Orofaciodigitales/diagnóstico , Neumonía Bacteriana/complicaciones , Antibacterianos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Femenino , Humanos , Lactante , Mutación , Síndromes Orofaciodigitales/complicaciones , Síndromes Orofaciodigitales/genética , Síndromes Orofaciodigitales/terapia , Neumonía Bacteriana/tratamiento farmacológico , Proteínas/genética , Calidad de Vida , Resultado del TratamientoRESUMEN
The proximate causes of multiple human genetic syndromes (ciliopathies) are disruptions in the formation or function of the cilium, an organelle required for a multitude of developmental processes. We previously identified Tmem107 as a critical regulator of cilia formation and embryonic organ development in the mouse. Here, we describe a patient with a mutation in TMEM107 that developed atypical Orofaciodigital syndrome (OFD), and show that the OFD patient shares several morphological features with the Tmem107 mutant mouse including polydactyly and reduced numbers of ciliated cells. We show that TMEM107 appears to function within cilia to regulate protein content, as key ciliary proteins do not localize normally in cilia derived from the Tmem107 mouse mutant and the human patient. These data indicate that TMEM107 plays a key, conserved role in regulating ciliary protein composition, and is a novel candidate for ciliopathies of unknown etiology.
Asunto(s)
Cilios/genética , Proteínas de la Membrana/genética , Mutación , Síndromes Orofaciodigitales/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Preescolar , Cilios/patología , Exoma , Fibroblastos/metabolismo , Fibroblastos/patología , Expresión Génica , Humanos , Masculino , Ratones , Datos de Secuencia Molecular , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/mortalidad , Cultivo Primario de Células , Alineación de SecuenciaAsunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Ciliopatías/diagnóstico , Fisura del Paladar/diagnóstico , Síndromes Orofaciodigitales/diagnóstico , Niño , Preescolar , Ciliopatías/diagnóstico por imagen , Ciliopatías/genética , Ciliopatías/patología , Fisura del Paladar/diagnóstico por imagen , Fisura del Paladar/genética , Fisura del Paladar/patología , Femenino , Feto/diagnóstico por imagen , Feto/patología , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/genética , Masculino , Síndromes Orofaciodigitales/diagnóstico por imagen , Síndromes Orofaciodigitales/genética , Síndromes Orofaciodigitales/patología , Diagnóstico Prenatal/métodosRESUMEN
Oral-facial-digital syndrome type VI (OFD VI) is a recessive ciliopathy defined by two diagnostic criteria: molar tooth sign (MTS) and one or more of the following: (1) tongue hamartoma (s) and/or additional frenula and/or upper lip notch; (2) mesoaxial polydactyly of one or more hands or feet; (3) hypothalamic hamartoma. Because of the MTS, OFD VI belongs to the "Joubert syndrome related disorders". Its genetic aetiology remains largely unknown although mutations in the TMEM216 gene, responsible for Joubert (JBS2) and Meckel-Gruber (MKS2) syndromes, have been reported in two OFD VI patients. To explore the molecular cause(s) of OFD VI syndrome, we used an exome sequencing strategy in six unrelated families followed by Sanger sequencing. We identified a total of 14 novel mutations in the C5orf42 gene in 9/11 families with positive OFD VI diagnostic criteria including a severe fetal case with microphthalmia, cerebellar hypoplasia, corpus callosum agenesis, polydactyly and skeletal dysplasia. C5orf42 mutations have already been reported in Joubert syndrome confirming that OFD VI and JBS are allelic disorders, thus enhancing our knowledge of the complex, highly heterogeneous nature of ciliopathies.
Asunto(s)
Proteínas de la Membrana/genética , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Anomalías Múltiples , Adolescente , Adulto , Alelos , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/genética , Cerebelo/anomalías , Niño , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Exoma , Anomalías del Ojo/diagnóstico , Anomalías del Ojo/genética , Femenino , Hamartoma/diagnóstico , Hamartoma/genética , Humanos , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/genética , Enfermedades Renales Quísticas/diagnóstico , Enfermedades Renales Quísticas/genética , Masculino , Mutación , Malformaciones del Sistema Nervioso/diagnóstico , Malformaciones del Sistema Nervioso/genética , Fenotipo , Polidactilia/diagnóstico , Polidactilia/genética , Retina/anomalías , Análisis de Secuencia de ADN , Adulto JovenAsunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas del Citoesqueleto/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Mutación , Síndromes Orofaciodigitales/diagnóstico , Síndromes Orofaciodigitales/genética , Fenotipo , Alelos , Sustitución de Aminoácidos , Biomarcadores , Preescolar , Genotipo , Humanos , Masculino , RadiografíaAsunto(s)
Síndromes Orofaciodigitales/diagnóstico , Diagnóstico Prenatal/métodos , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Femenino , Edad Gestacional , Humanos , Imagen por Resonancia Magnética , Masculino , Proteínas de la Membrana/genética , Mutación , Síndromes Orofaciodigitales/genética , Síndromes Orofaciodigitales/patología , Embarazo , Segundo Trimestre del Embarazo , Hermanos , Ultrasonografía PrenatalAsunto(s)
Acné Vulgar/genética , Agenesia del Cuerpo Calloso/genética , Síndromes Orofaciodigitales/genética , Proteínas/genética , Acné Vulgar/etiología , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Agenesia del Cuerpo Calloso/etiología , Femenino , Mutación del Sistema de Lectura , Humanos , Lactante , Ventrículos Laterales/anomalías , Ventrículos Laterales/diagnóstico por imagen , Síndromes Orofaciodigitales/complicaciones , Síndromes Orofaciodigitales/diagnósticoRESUMEN
We report a patient with oral-facial-digital syndrome type 1 (OFDS1) who exhibited features overlapping those of nevus comedonicus syndrome, an unusual presentation that may potentially represent a new variant of OFDS1. OFDS1 and nevus comedonicus syndrome represent two rare syndromes with numerous overlapping features that have yet to be described in relation to one another. The features present in our patient led us to propose the possibility of a new variant of OFDS1 in which nevus comedonicus represents a cutaneous manifestation of the syndrome. Knowledge of this potential relationship is important for identification and management of the syndromes' accompanying manifestations in affected patients and may offer further insight into crossroads of pathogenesis.
Asunto(s)
Neoplasias Faciales/diagnóstico , Nevo/diagnóstico , Síndromes Orofaciodigitales/diagnóstico , Neoplasias Cutáneas/diagnóstico , Preescolar , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
UNLABELLED: Ciliopathies are phenotypically and genetically heterogeneous disorders that share ciliary dysfunction as a common pathological mechanism. Ciliary dysfunction results in a broad range of malformations including renal, hepatic and pancreatic cysts, visceral abnormalities, retinal degeneration, anosmia, cerebellar or other brain anomalies, polydactyly, bronchiectasis and infertility. The paper presents a familial case of oral-facial-digital syndrome type 1 in 14 year old girl suspected to polycystic kidney disease. CONCLUSIONS: Molecular testing in daughters of known OFD1 mutation carriers and mothers of affected daughters seems to be reasonable. Not each case of policystic kidney disease which looks like autosomal dominant policystic kiedney disease is actually the above disease. The insight into the pathogenesis of ciliopathies is mandatory for understanding these combined congenital anomaly syndromes of seemingly unrelated symptoms of hepatorenal and pancreatic fibrocystic disease. Close interdisciplinary approach is mandatory in terms of efficient and reliable diagnostic and therapeutic interventions in patients presenting with ciliopathies.
Asunto(s)
Síndromes Orofaciodigitales/diagnóstico , Adolescente , Diagnóstico Diferencial , Femenino , Humanos , Síndromes Orofaciodigitales/genética , Enfermedades Renales Poliquísticas/diagnósticoRESUMEN
BACKGROUND: Oro-facial digital(OFD) syndrome is a rare anomaly which is often missed out as just cleft lip and palate.It is an X-linked dominant condition with lethality in males. It however results from the pleotropic effect of a morphogenetic impairment affecting almost invariably the mouth, face and digits and it also includes lower IQ and mental retardation. 14 different variations of these syndrome can be seen with the majority of cases of type 1 and 2 based on characteristic clinical manifestations. CASE REPORT: Present case report describes a 9 year old girl patient who was mis-diagnosed with partial cleft palate and was later diagnosed as orofacial digital syndrome based on the clinical and oral features. CONCLUSION: Not much literature is present regarding this topic and with no relevent family history makes this case a one in a million case of OFD. Therefore, this case report is a complete insight on Oro-facial digital syndrome.
Asunto(s)
Labio Leporino , Fisura del Paladar , Anomalías de la Boca , Síndromes Orofaciodigitales , Masculino , Femenino , Humanos , Niño , Fisura del Paladar/diagnóstico , Síndromes Orofaciodigitales/diagnóstico , CaraRESUMEN
A hamartoma is a benign proliferation of typical mature cells specific to a particular anatomical site. In the oral cavity, they may occur as isolated cases or be associated with genetic syndromes. Oral-facial-digital syndrome type VI is a rare genetic disorder with an estimated incidence of one in 50,000-250,000 newborns. Here, we report a case of a 2-year-old boy diagnosed with oral-facial-digital syndrome type VI who was referred for evaluation of a bilateral and normochromic to slightly pinkish nodule on the lateral surface of the tongue. Clinically, the child presented hypotonia, low visual acuity, absence of oculocephalic reflex, delay in neuropsychomotor development, and polydactyly in the feet. Excisional biopsies of both sides of the tongue were performed using a 1.5 W high-power diode laser (wavelength of 980 nm), and histopathological analysis revealed abundant mature adipocytes predominantly arranged in lobules that mainly surrounded the minor salivary gland parenchyma. The surgical sites healed with no complications and the patient remains under follow-up for 10 months. Due to the limited literature on this syndrome and the frequent presence of tongue hamartomas in children, dentists need to be familiar with them.
Asunto(s)
Hamartoma , Síndromes Orofaciodigitales , Enfermedades de la Lengua , Humanos , Hamartoma/patología , Masculino , Síndromes Orofaciodigitales/patología , Síndromes Orofaciodigitales/diagnóstico , Preescolar , Enfermedades de la Lengua/patología , Enfermedades de la Lengua/diagnóstico , BiopsiaRESUMEN
This article describes an infant who had a combination of malformations. The boy had a median cleft of the lip, cleft of the soft palate, microcephaly, and ulnar polydactyly of both hands and feet. All of these are relatively commonly encountered in any plastic surgical outpatient department. However, the combination of such abnormalities is encountered extremely rarely. Thurston syndrome is one of the several oral-facial-digital syndromes. A brief literature review of Thurston syndrome and salient features of oral-facial-digital syndromes are discussed.
Asunto(s)
Síndromes Orofaciodigitales/diagnóstico , Humanos , Lactante , Masculino , Síndromes Orofaciodigitales/cirugíaRESUMEN
Oro-facial-digital syndrome type II (OFD-II) is characterized by frenulated tongue, midline cleft lip, high arched or cleft palate, micrognathia, syndactyly and polydactyly, bilateral reduplicated hallux, conductive hearing loss, choroidal coloboma and normal intelligence. There are nine forms of oro-facial-digital syndromes with different modes of inheritance. A young female with features of oro-facio-digital syndrome type-II is being reported.