RESUMEN
We report on a newborn boy with a bilateral cleft of the primary palate, duplicated triphalangeal thumbs, and a patent foramen ovale. During childhood he had moderate developmental delay. Brain MRI at 4 years was normal. The concurrence of non-syndromic clefts of the lip/palate (CL/P) and duplicated thumbs with triphalangeal component has, to our knowledge, not been reported so far. In our case, array-CGH analysis documented two de novo deletions (â¼1.2 Mb and â¼400 Kb) of the long arm of chromosome 4, containing four genes: platelet-derived growth factor C (PDGFC), glycine receptor beta subunit (GLRB), glutamate receptor ionotropic AMPA2 (GRIA2), and F-box protein 8 gene (FBXO8). PDGFC codes for a mesenchymal cell growth factor already known to be associated with clefts of the lip. Pdgfc(-/-) mice have skeletal anomalies, and facial schisis resembling human cleft/lip palate. GRIA2 codes for a ligand-activated cation channel that mediates the fast component of postsynaptic excitatory currents in neurons, and may be linked to cognitive dysfunction. FBXO8, a gene of unknown function, is a member of the F-box gene family, among which FBXW4, within the minimal duplicated region associated with human split-hand/foot malformation type 3 (SHFM type 3). The presence of overlapping deletions in patients who do not share the same phenotype of our case suggests incomplete penetrance, and a possible effect of modifier genetic factors.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 4 , Labio Leporino/genética , Deformidades Congénitas de la Mano/genética , Pulgar/anomalías , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Animales , Labio Leporino/diagnóstico , Hibridación Genómica Comparativa , Deformidades Congénitas de la Mano/diagnóstico , Humanos , Recién Nacido , Linfocinas/genética , Masculino , Ratones , Linaje , Fenotipo , Factor de Crecimiento Derivado de Plaquetas/genética , Receptores AMPA/genética , SíndromeRESUMEN
Beckwith-Wiedemann syndrome is an overgrowth disorder characterized by neonatal macrosomia, abdominal wall defects, macroglossia, renal anomalies, organomegaly, hypoglycemia, and cancer predisposition. Hepatoblastoma is the second most frequent tumor and periodic serum alpha-fetoprotein (αFP) dosage is the cornerstone of the tumor surveillance for its early detection. In this report, we describe the outstanding case of a Beckwith-Wiedemann syndrome (BWS) newborn with severe phenotype and paternal chromosome 11 uniparental disomy (UPD11) associated with a high tumor risk. Based on the clinical picture and previous reports, a close monitoring of αFP was commenced. The marker was normal immediately after birth, but rapidly raised in 20 days, leading to the diagnosis of an extremely aggressive hepatoblastoma. The latter was successfully treated with pre-surgical reductive chemotherapy, gross total mass resection, and subsequent chemotherapy. Based on this observation, the tumor surveillance routinely suggested every 3 months should be more intense and with closer time intervals in newborns with severe BWS phenotype. We suggest monitoring neonatal αFP every 20 days in such cases.
Asunto(s)
Síndrome de Beckwith-Wiedemann , Hepatoblastoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , alfa-Fetoproteínas/metabolismo , Síndrome de Beckwith-Wiedemann/genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Predisposición Genética a la Enfermedad , Hepatoblastoma/genética , Humanos , Recién Nacido , Factor II del Crecimiento Similar a la Insulina/metabolismo , Neoplasias Hepáticas/genética , MasculinoRESUMEN
BACKGROUND: Orofacial clefts are common congenital malformations usually characterized by a multifactorial etiology. These heterogeneous defects comprise cleft lip (CL), CL with cleft palate (CL/P), and cleft palate, sometimes observed in recognizable syndromes, with mendelian, chromosomal, or environmental pathogenesis. The Van der Woude syndrome is a mendelian CL/P, accounting for about 2% of all cases and caused by mutations in the interferon regulatory factor 6 (IRF6) gene, located on 1q32.2 chromosome. OBJECTIVE: Here, we describe a familial case with a novel IRF6 mutation segregating in the maternal line, displaying a highly intrafamilial variable clinical expression. CONCLUSION: This report emphasizes the role of the clinician in recognizing the clinical variability and the genetic heterogeneity of CL/P.
Asunto(s)
Anomalías Múltiples , Cromosomas Humanos Par 1 , Labio Leporino/genética , Fisura del Paladar/genética , ADN/genética , Predisposición Genética a la Enfermedad , Factores Reguladores del Interferón/genética , Mutación , Labio Leporino/diagnóstico , Fisura del Paladar/diagnóstico , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Factores Reguladores del Interferón/metabolismo , LinajeRESUMEN
OBJECTIVE: Many authors consider surgical therapy of pediatric ranula and intraoral mucocele as the election treatment. Recently, an intracystic sclerosing injection with OK-432 has been proposed as a ranula primary treatment. This preliminary study evaluates the effectiveness of the use of Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations as the primary treatment of pediatric ranula and intraoral mucocele. METHODS: Eighteen children (9 ranulas, 9 labial mucoceles, 2 lingual mucoceles) were treated with oral administration of Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations D10/D30/D200. RESULTS: Eighty-nine percent ranulas (8 out of 9), 67% labial mucoceles (6 out of 9) completely responded to the therapy. One ranula, that interrupted therapy after only 4 weeks, was subjected to marsupialization in another hospital. A double mucocele case partially responded (one of the two was extinguished), another case incompletely responded, decreasing the size beyond 50%, and just one case, changing volume, resisted the therapy. Lingual mucocele healed at once. Blandin-Nuhn polypoid congenital mucocele responded to the treatment with gradual reabsorption, permitting surgical excision of the atrophic polypoid remnant, without removing glands of origin. No solved case showed recurrence (follow up range: 4-32 months). CONCLUSION: Homotoxicological therapy with Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations D10/D30/D200 is an effective primary treatment of pediatric ranula and intraoral mucocele.
Asunto(s)
Gluconatos/uso terapéutico , Homeopatía , Compuestos de Mercurio/uso terapéutico , Enfermedades de la Boca/tratamiento farmacológico , Mucocele/tratamiento farmacológico , Níquel/uso terapéutico , Ránula/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoRESUMEN
A girl with oral, facial, and digital anomalies presented at birth with a large cleft palate filled by a nasopharyngeal mass and was found later to have several vertebral anomalies and mental retardation. A similar phenotype has been previously reported in a sporadic male patient [Gabrielli et al., 1994: Am J Med Genet 53:290-293], suggesting a new variant form of oral-facial-digital syndrome.
Asunto(s)
Anomalías Múltiples/genética , Trastornos Psicomotores/genética , Anomalías Múltiples/fisiopatología , Encéfalo/patología , Femenino , Humanos , Lactante , Recién Nacido , Cuello/patología , Trastornos Psicomotores/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
We report on an Italian boy, born to normal and nonconsanguineous parents with a prenatal diagnosis of ventriculomegaly and subependymal glial heterotopias. At birth bilateral macrostomia was diagnosed without other evident facial anomalies. Magnetic resonance imaging (MRI) showed triventricular hydrocephalus and aqueductal stenosis and confirmed the nodules of glial heterotopia. The bilateral macrostomia was surgically corrected with the vermilion square flap method and W-plasty technique and follow up MRI at 6 months showed mild increase of ventricular dilatation without signs of active hydrocephalus. The association between macrostomia and hydrocephalus has been reported only in rare cases of complex malformative syndromes but never with isolated macrostomia.