RESUMEN
Background: Multiple congenital anomalies-hypotony-seizures syndrome 3 (MCAHS3) is a rare autosomal recessive disorder caused by mutations in the PIGT gene. PIGT encodes phosphatidylinositol-glycan biosynthesis class T, which plays a crucial role in protein anchoring to cell membranes. The clinical presentation of MCAHS3 is variable in expression and severity, but can be characterized by developmental delay, seizures, hypotonia, facial dysmorphism, and other abnormalities.Materials and Methods: Case report.Results: We report unusual ocular findings including bilateral anterior segment dysgenesis, avascular retinal periphery, and tractional retinal detachment in a 1-month-old male infant with compound heterozygous PIGT mutations consistent with MCAHS3. Whole-exome sequencing did not detect any other genetic abnormalities.Conclusions: This case expands the clinical spectrum of MCAHS3 to include anomalies in ocular anterior segment and retinal vascular development. Given the rarity and the genetic heterogeneity of MCAHS3, giving rise to varied non-ocular phenotypes, it is possible that milder intraocular phenotypes could have gone unrecognized in the past.
Asunto(s)
Anomalías Múltiples/genética , Aciltransferasas/genética , Epilepsia/genética , Anomalías del Ojo/genética , Isquemia/genética , Hipotensión Ocular/genética , Desprendimiento de Retina/genética , Anomalías Múltiples/diagnóstico , Epilepsia/diagnóstico , Anomalías del Ojo/diagnóstico , Angiografía con Fluoresceína , Humanos , Lactante , Isquemia/diagnóstico , Masculino , Mutación/genética , Hipotensión Ocular/diagnóstico , Desprendimiento de Retina/diagnóstico , Vasos Retinianos/patología , Nacimiento a TérminoRESUMEN
BACKGROUND: The ß adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic ß blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes. MATERIALS AND METHODS: Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing. RESULTS: There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 ± 1.2 - follow-up IOP 13.6 ± 2.0 (mean difference-2.5 ± 1.3, p < 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 ± 1.2 mmHg versus 16.0 ± 1.2 mmHg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 ± 1.1 mmHg versus -0.7 ± 0.4 mmHg; p < 0.001). Gln27 had a higher response than Glu27 (-2.7 ± 1.3 mmHg versus -1.9 ± 1.0; p = 0.02). CONCLUSION: Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.
Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Betaxolol/administración & dosificación , Presión Intraocular/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Administración Tópica , Adulto , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Femenino , Frecuencia de los Genes , Genotipo , Voluntarios Sanos , Humanos , Presión Intraocular/genética , Masculino , México , Persona de Mediana Edad , Hipotensión Ocular/inducido químicamente , Hipotensión Ocular/genética , Soluciones Oftálmicas , Reacción en Cadena de la Polimerasa , Tonometría OcularRESUMEN
We describe a father-son Mexican pair with typical features of Schilbach-Rott syndrome (SRS): ocular hypotelorism, cleft palate, hypospadias (only in the child), and microcephaly. This observation documents for the first time a male to male transmission and therefore confirms that the SRS is inherited as an autosomal dominant trait with variable expressivity.
Asunto(s)
Anomalías Múltiples/genética , Fisura del Paladar/genética , Hipospadias/genética , Adulto , Cesárea , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Núcleo Familiar , Hipotensión Ocular/genética , SíndromeRESUMEN
PURPOSE: We present the clinical, genetic and histopathologic findings in two siblings with Muscle-Eye-Brain Disease (MEB-D), an autosomal recessive disease characterized by mental retardation, muscular dystrophy, retinal hypoplasia and brain abnormalities. METHODS: Clinical, histopathologic and gene mapping studies of a family with two normal and two children with MEB-D. RESULTS: Two siblings presented in the first few months of life with developmental delay, hypotonia, and strabismus. MRI of the brain showed colpocephaly, pontine and cerebellar atrophy, and diffuse white matter disease. Both patients were blind and had high myopia, strabismus, and retinal and optic nerve abnormalities. The older boy had glaucoma. Both children died from uncontrolled seizures. There was retinal, choroidal and RPE atrophy and optic nerve hypoplasia on ocular histopathology. Both patients shared the same parental haplotypes at the MEB locus on chromosome 1p, while an unaffected sibling did not, indicating possible linkage to the MEB locus. CONCLUSIONS: Patients with MEB-D have severe visual impairment from retinal and optic nerve hypoplasia. High myopia appears to be a consistent finding. The ocular manifestations of MEB-D appear to be distinct from those of patients with Walker-Warburg syndrome.
