Mutación c.3037G>A en el gen FBN1 asociado a síndrome de Marfan variante neonatal / Mutation c.3037G>A in the FBN1 gene associated with neonatal Marfan syndrome variant

Resumen: El síndrome de Marfan ([SM], OMIM 154700) es un trastorno del tejido conectivo que exhibe un patrón de herencia autosómico dominante, cuyas características clínicas pueden afectar de forma variable múltiples sistemas u órganos. Es causado por mutaciones en el gen FBN1 (OMIM 134797) localizado en 15q21.1. El SM neonatal es una variedad infrecuente de la entidad asociado con mutaciones en el cambio de sentido entre los exones 23-33 y mutaciones truncadas, exhibe un fenotipo más severo y alto porcentaje de mortalidad en los primeros años de vida. Se presenta el caso de adolescente masculino con SM neonatal y mutaciones en el cambio de sentido (c.3037G>A; p.Gly225Arg) en el exón 24 del gen FBN1. Ante estos hallazgos se estudió la variación fenotípica interfamiliar, la evaluación médica interdisciplinaria precoz necesaria para el manejo de las posibles complicaciones, así como el oportuno asesoramiento genético familiar.

Abstract: Marfan syndrome ([MS], OMIM 154700) is a connective tissue disorder that exhibits an autosomal dominant pattern of inheritance, whose clinical characteristics can affect multiple systems or organs in a variable way. It is caused by mutations in the FBN1 gene (OMIM 134797) located at 15q21.1. Neonatal MS is an uncommon variety of the entity associated with missense mutation between exons 23-33 and truncating mutations, exhibits a more severe phenotype and high percentage of mortality in the first years of life. The case of male adolescent with neonatal MS and missense mutation (c.3037G> A; p.Gly225Arg) in exon 24 of the FBN1 gene is presented. Given these findings, interfamilial phenotype variation, the early interdisciplinary medical evaluation necessary for the management of possible complications, as well as the appropriate family genetic counseling were studied.

[Mutation c.3037G>A in the FBN1 gene associated with neonatal Marfan syndrome variant]. / Mutación c.3037G>A en el gen FBN1 asociado a síndrome de Marfan variante neonatal.

Marfan syndrome ([MS], OMIM 154700) is a connective tissue disorder that exhibits an autosomal dominant pattern of inheritance, whose clinical characteristics can affect multiple systems or organs in a variable way. It is caused by mutations in the FBN1 gene (OMIM 134797) located at 15q21.1. Neonatal MS is an uncommon variety of the entity associated with missense mutation between exons 23-33 and truncating mutations, exhibits a more severe phenotype and high percentage of mortality in the first years of life. The case of male adolescent with neonatal MS and missense mutation (c.3037G> A; p.Gly225Arg) in exon 24 of the FBN1 gene is presented. Given these findings, interfamilial phenotype variation, the early interdisciplinary medical evaluation necessary for the management of possible complications, as well as the appropriate family genetic counseling were studied.

El síndrome de Marfan ([SM], OMIM 154700) es un trastorno del tejido conectivo que exhibe un patrón de herencia autosómico dominante, cuyas características clínicas pueden afectar de forma variable múltiples sistemas u órganos. Es causado por mutaciones en el gen FBN1 (OMIM 134797) localizado en 15q21.1. El SM neonatal es una variedad infrecuente de la entidad asociado con mutaciones en el cambio de sentido entre los exones 23-33 y mutaciones truncadas, exhibe un fenotipo más severo y alto porcentaje de mortalidad en los primeros años de vida. Se presenta el caso de adolescente masculino con SM neonatal y mutaciones en el cambio de sentido (c.3037G>A; p.Gly225Arg) en el exón 24 del gen FBN1. Ante estos hallazgos se estudió la variación fenotípica interfamiliar, la evaluación médica interdisciplinaria precoz necesaria para el manejo de las posibles complicaciones, así como el oportuno asesoramiento genético familiar.

Gait assessment for neurologically impaired patients. Standards for outcome assessment.

This study compared the temporal-distance (TD) gait values of two groups of neurologically impaired subjects with published TD gait values of healthy subjects and analyzed the influence of nine clinical characteristics on TD values in the neurologically impaired subjects. Velocity, cadence, step length, stride length, and ratio of stride length to lower extremity length were recorded for 37 subjects with hemiparesis and 24 subjects with multiple sclerosis. Temporal-distance values were well below normal values, even in functionally independent subjects. Overall, the subjects with hemiparesis had lower values than the subjects with multiple sclerosis. Of the nine characteristics examined, only diagnosis, etiologic factor (for hemiparesis), type of ambulation aid, and functional category were related significantly to TD values. Our findings suggest that TD gait performance goals for patients with neurological impairment should be based on values from impaired rather than healthy subjects and that these goals should be adjusted for the individual patient's diagnosis, etiologic factor, type of ambulation aid, and functional category.

Clinical gait assessment in the neurologically impaired. Reliability and meaningfulness.

This study of subjects with multiple sclerosis or hemiparesis assessed the interrater and test-retest reliability of temporal-distance (TD) gait measures and examined the relationship of TD values to functional ambulation ability. Sixty-one subjects ambulated twice on a 9-m (30-ft) paper walkway and rested 15 minutes between trials. An ink footprint record and ambulation time were used to calculate velocity, cadence, step and stride lengths, stride length to lower extremity length ratio, and step- and stride-time differentials. Subjects were rated on a scale that assessed the amount of manual assistance required for ambulation. Interrater and test-retest reliability were high for all TD measures except stride-time differential for the total sample and within diagnostic categories. The TD values were highly reliable in all functional categories except one. All TD measures except stride- and step-time differential displayed a strong linear relationship to the functional ambulation category. Implications for using TD measures in clinical settings are discussed.