RESUMEN
Neocentromeres are mitotically stable human derivative centromeres without alpha-satellite DNA which are able to provide stability to rearranged chromosome fragments that would otherwise be acentric and rapidly lost. A female fetus was found to be mosaic for a supernumerary marker chromosome: 47,XX,+mar[3]/46,XX[36]. The marker was identified by fluorescence in situ hybridization and G-band as an inversion duplication of 13q21â13qter, with a neocentromere present at 13q21, in approximately 9% of colonies examined. Parental blood karyotypes were normal. QF-PCR performed on blood samples from both parents and the second amniotic fluid sample showed evidence of a second maternal allele at markers D13S258 (13q21) and D13S628 (13q31-q32), indicating formation at maternal meiosis I/II. This is the first reported case where the detection and origin of a low-level mosaic prenatal neo(13) were confirmed by QF-PCR.
Asunto(s)
Centrómero , Duplicación Cromosómica , Inversión Cromosómica , Cromosomas Humanos Par 13 , Adulto , Amniocentesis , Femenino , Humanos , Masculino , Mosaicismo , Reacción en Cadena de la Polimerasa , EmbarazoRESUMEN
At a consensus meeting held in Montreal, October 28, 2011, a multidisciplinary group of Canadian experts in the fields of genetics, gastroenterology, surgery, oncology, pathology, and health care services participated in presentation and discussion sessions for the purpose of developing consensus statements pertaining to the development and maintenance of hereditary colorectal cancer registries in Canada. Five statements were approved by all participants.
RESUMEN
The hereditary stomatocytoses are a group of heterogeneous conditions associated with chronic red cell hemolysis for which the causative genetic mutations are not known. We investigated 137 members of a large Canadian kindred with phenotypic findings consistent with hereditary xerocytosis, one of the most common stomatocytosis syndromes. The objectives of this study were to characterize the clinical hallmarks of the hemolytic process, and to define the chromosomal region carrying the disease locus. The mode of inheritance was autosomal dominant. Affected family members had a well-compensated hemolysis, associated with an elevated MCHC, decreased osmotic fragility, decreased haptoglobin, and indirect hyperbilirubinemia. Cholelithiasis and progressive iron loading were common, despite normal hemoglobin levels. Quantitative erythrocyte morphologic evaluation revealed increased schistocytes, target cells, reticulocytes, and eccentrocytes in affected individuals; stomatocytes were not increased. Genetic linkage analysis confirmed the localization of the disease phenotype to chromosome 16q, and refined the candidate region to 16q24.2-16qter, a 2.4 million base pair interval containing 51 known or predicted genes.
Asunto(s)
Anemia Hemolítica Congénita/genética , Cromosomas Humanos Par 16 , Sitios Genéticos , Hidropesía Fetal/genética , Adolescente , Adulto , Anemia Hemolítica Congénita/patología , Canadá , Niño , Mapeo Cromosómico , Femenino , Ligamiento Genético , Haplotipos , Humanos , Hidropesía Fetal/patología , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Adulto JovenRESUMEN
We report on a patient with sleep apnea and an unusual familial movement disorder. The movements were present only during wakefulness and nocturnal arousals caused by disordered breathing. A 27-year-old obese man was referred with sleep onset insomnia, symptoms suggesting restless legs syndrome, daytime sleepiness, loud snoring and awakening with choking sensations. He was proven to have obstructive sleep apnea (apnea hypopnea index = 60.6). He also had a daytime movement disorder that was characterized by almost continuous stereotypic tapping of one or both legs. The movements were suppressible and not associated with any unpleasant or abnormal leg sensation. Virtually identical movements were present in three generations of his family. The severity of the movements did not worsen late in the day or with supine posturing. The nocturnal movements, consisting of a visible shaking of one or both legs, occurred only during arousals secondary to the apnea, had a mean duration of 5.7 +/- 3.0 (standard deviation) seconds and could not be defined as periodic limb movements in sleep (PLMS). Successful treatment of apnea by nasal continuous positive airway pressure dramatically reduced the movements during sleep (from 88.2 to 1.9 per hour). The clinical significance and the mechanism of this movement disorder is unknown. We discuss the features inconsistent with restless legs syndrome and consider other possible phenomenology, including akathisia. We conclude that this patient may have a previously unreported familial movement disorder and in addition developed the sleep apnea syndrome related to obesity.
Asunto(s)
Pierna , Trastornos del Movimiento/complicaciones , Trastornos del Movimiento/genética , Síndrome de las Piernas Inquietas , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/genética , Vigilia , Adulto , Nivel de Alerta , Consanguinidad , Diagnóstico Diferencial , Humanos , Masculino , Trastornos del Movimiento/diagnóstico , Linaje , Síndrome de las Piernas Inquietas/diagnóstico , Síndromes de la Apnea del Sueño/diagnósticoRESUMEN
We report on a father and son with mild Brachmann-de Lange syndrome. Previous reports have documented apparent autosomal dominant transmission; however, only one example of male-to-male transmission of possible Brachmann-de Lange syndrome has been reported. This case provides further evidence of the existence of an autosomal dominant form of Brachmann-de Lange syndrome.
Asunto(s)
Síndrome de Cornelia de Lange/genética , Adulto , Preescolar , Síndrome de Cornelia de Lange/patología , Discapacidades del Desarrollo/genética , Cara/anomalías , Genes Dominantes , Trastornos del Crecimiento/genética , Humanos , Masculino , FenotipoRESUMEN
Although limb and renal defects occur together in a variety of patterns of multiple malformations, familial cases of acro-renal disorders are rare. In 1980, Halal et al. ¿Am J Med Genet 5:277-284 described two sisters with unusual limb deficiencies, renal anomalies, and mandibular hypoplasia and termed this condition acro-renal-mandibular syndrome. A girl reported earlier by Fitch and Lachance ¿1972; Can Med Assoc J 107:653-656 had similarly limb and renal findings, but an apparently normal jaw. We document three sibs with unusual limb deficiencies, renal agenesis, uterine anomalies in the two females, and orofacial defects, who clearly have a similar but more severe type of acrorenal disorder, apparently inherited as an autosomal recessive condition. The sibs with limb deficiencies and renal agenesis reported by Hennekam et al. ¿1994; Am J Med Genet 53:102-107 appear to be additional cases of this very rare disorder, the pathogenesis of which may be related to abnormal epithelial-mesenchymal interactions.
Asunto(s)
Anomalías Múltiples/patología , Anomalías Maxilomandibulares/patología , Riñón/anomalías , Deformidades Congénitas de las Extremidades/patología , Útero/anomalías , Femenino , Humanos , Recién Nacido , Masculino , Linaje , SíndromeRESUMEN
This study was undertaken to evaluate the relationship between elevated maternal serum alpha fetoprotein (MSAFP) levels and congenital heart defects. Thirty-two infants with isolated major congenital heart defects and whose mothers had had MSAFP screening were identified. In only one case was the MSAFP greater than 2.3 multiples of the median. A review of our experience with women with elevated MSAFP levels did not document a higher rate of congenital heart malformations than would be expected based on estimated frequencies in the general population.
Asunto(s)
Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/diagnóstico , alfa-Fetoproteínas/metabolismo , Biomarcadores , Femenino , Edad Gestacional , Cardiopatías Congénitas/epidemiología , Humanos , Recién Nacido , Tamizaje Masivo , Intercambio Materno-Fetal , Embarazo , Diagnóstico Prenatal , Factores de RiesgoRESUMEN
We describe a child who was born with marked digital hypoplasia of his right hand. Although the mother was not an epileptic, the child was exposed in utero to diphenylhydantoin.
Asunto(s)
Anomalías Inducidas por Medicamentos/etiología , Dedos/anomalías , Fenitoína/efectos adversos , Adulto , Malformaciones Arteriovenosas/complicaciones , Malformaciones Arteriovenosas/cirugía , Hemorragia Cerebral/complicaciones , Dermatoglifia , Femenino , Humanos , Recién Nacido , Masculino , Intercambio Materno-Fetal , Fenitoína/uso terapéutico , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Convulsiones/prevención & controlRESUMEN
A young man was diagnosed as having Zimmerman-Laband syndrome (ZLS) on the basis of gingival fibromatosis and absence of nails on thumbs and halluces in addition to other anomalies. He also had profound mental retardation.
Asunto(s)
Hipertrofia Gingival/complicaciones , Discapacidad Intelectual/complicaciones , Uñas Malformadas , Adulto , Cara/anomalías , Genes Dominantes , Mano/diagnóstico por imagen , Humanos , Masculino , Radiografía , Escoliosis/complicaciones , Convulsiones/complicaciones , SíndromeRESUMEN
We report on 8 (3 male, 5 female) native Canadian children with distinctive facial appearance and variable combinations of ocular colobomas, hypertelorism, macrocephaly, hand anomalies, congenital heart defects, structural CNS posterior fossa malformations, and mental retardation. These 8 children belong to 7 families; 3 of the families are related. The parents and other sibs are clinically unaffected. We think these manifestations provide evidence for Ritscher-Schinzel syndrome in native Canadian children, and we have confirmed that ocular colobomas are a common occurrence in this disorder.
Asunto(s)
Anomalías Múltiples/genética , Indígenas Norteamericanos/genética , Canadá , Femenino , Humanos , Recién Nacido , Masculino , Linaje , SíndromeRESUMEN
We present a girl with ring chromosome 16. Clinical abnormalities included developmental delay, short stature, and minor facial anomalies. Analysis of the glutamate-pyruvate transaminase (GPT) phenotype suggests the possible exclusion of the GPT locus expressed in erythrocytes (GPT) from the very distal p13 region of chromosome 16.
Asunto(s)
Aberraciones Cromosómicas , Cromosomas Humanos Par 16 , Discapacidades del Desarrollo/genética , Huesos Faciales/anomalías , Trastornos del Crecimiento/genética , Cromosomas en Anillo , Alanina Transaminasa/genética , Preescolar , Bandeo Cromosómico , Discapacidades del Desarrollo/complicaciones , Femenino , Trastornos del Crecimiento/complicaciones , Humanos , Cariotipificación , FenotipoRESUMEN
Williams syndrome (WS) is associated with a deletion of the elastin gene in over 90% of cases. We report maternal serum alpha feto-protein (MSAFP) levels in 5 women whose fetuses were later diagnosed as having WS. MSAFP levels ranged from 0.5-0.8 multiples of the median (MOM). Although further confirmation is necessary, it appears that MSAFP levels are lower than the median in WS. This apparent association has implications for counselling women following maternal serum screening.
Asunto(s)
Embarazo/sangre , Síndrome de Williams/sangre , alfa-Fetoproteínas/metabolismo , Femenino , Humanos , Diagnóstico Prenatal , Síndrome de Williams/diagnósticoRESUMEN
Williams-Beuren syndrome (WBS) results from a deletion of 7q11.23 in 90-95% of all clinically typical cases. Clinical manifestation can be variable and therefore, deletion size, inherited elastin (ELN) and LIM kinase 1 (LIMK1) alleles, gender, and parental origin of deletion have been investigated for associations with clinical outcome. In an analysis of 85 confirmed deletion cases, no statistically significant associations were found after Bonferroni's correction for multiple pairwise comparisons. Furthermore, the present data do not support presence of imprinted genes in the WBS common deletion despite a nonsignificant excess of maternal over paternal deletions. Maternal deletion cases were more likely to have a large head circumference in the present data. Also, pairwise comparisons between individual WBS clinical features have been conducted and revealed significant associations between (1) low birth weight and poor postnatal weight gain (<10th percentile at the time of examination) and (2) transient infantile hypercalcemia and a stellate iris pattern. The latter association could indicate a common underlying etiology.
Asunto(s)
Cromosomas Humanos Par 7/genética , Impresión Genómica/genética , Eliminación de Secuencia/genética , Síndrome de Williams/genética , Alelos , Peso al Nacer , Elastina/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Hipercalcemia , Recién Nacido , Quinasas Lim , Desequilibrio de Ligamiento , Masculino , Fenotipo , Polimorfismo Genético/genética , Proteínas Quinasas/genética , Aumento de Peso , Síndrome de Williams/etiología , Síndrome de Williams/fisiopatologíaRESUMEN
We describe five patients with Fryns syndrome. Four presented with diaphragmatic hernia and died in the neonatal period. One did not have diaphragmatic involvement and survived but is severely mentally retarded. All patients had "coarse" faces, microretrognathia, macrostomia, and distal digital hypoplasia. In addition to previously reported traits, our patients had clinical manifestations that have not previously been described, including omphalocele, broad clavicles, Hirschsprung "disease," and anal anomalies. The condition was detected antenatally in three of the cases. The patients include two sib pairs, further supporting autosomal recessive inheritance.
Asunto(s)
Anomalías Múltiples/genética , Expresión Facial , Genes Recesivos , Hernias Diafragmáticas Congénitas , Discapacidad Intelectual/genética , Deformidades Congénitas de las Extremidades , Femenino , Humanos , Recién Nacido , Masculino , Diagnóstico Prenatal , Síndrome , UltrasonografíaRESUMEN
We undertook a retrospective etiological study of all children referred for evaluation of pervasive developmental disorder (PDD). We identified 91 children who met the DSM III-R criteria for PDD. Fifty-two were diagnosed with autistic disorder (AD), and 39 with PDD-not otherwise specified (PDD-NOS). Seven families (8.2%) had more than one affected sib. The overall recurrence rate was 7.1%. Six families had a positive history of PDD in more distant relatives. An excess of developmental problems were identified on the maternal side (seven families, vs two families on the paternal side). Affected children had head circumferences above the mean when compared with standardized growth curves. A recognizable syndrome or genetic disorder was identified in 14 children (15.4%), of which 8 children (9%) were thought to be causative of PDD (5 children with Rett syndrome, 2 with fragile X syndrome, and 1 with velocardiofacial syndrome [VCFS]). Six others had a recognized genetic, cytogenetic, or metabolic disorder believed to be unrelated to the PDD diagnosis. Given the relatively high yield of genetic diagnoses in this population, we believe that children with PDD-NOS or AD should have a detailed evaluation by a clinical geneticist or pediatrician trained in dysmorphology. Chromosome anomalies, fragile X, and other recognizable disorders, including VCFS, need to be excluded. The value of general screening for an inborn error of metabolism in all children with PDD is not certain. In light of the relatively high recurrence of PDD in families, genetic counseling is recommended.
Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/genética , Adolescente , Trastorno Autístico/psicología , Niño , Trastornos Generalizados del Desarrollo Infantil/complicaciones , Trastornos Generalizados del Desarrollo Infantil/metabolismo , Aberraciones Cromosómicas , Trastornos de los Cromosomas , Femenino , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Escalas de Valoración Psiquiátrica , Recurrencia , Estudios Retrospectivos , Convulsiones/complicacionesRESUMEN
Maternal serum alpha-fetoprotein (MSAFP) levels in 529 non-diabetic aboriginal Canadian women were compared with levels in 13,285 non-diabetic non-aboriginal women. A woman was considered to be aboriginal if she was listed on the Indian Register of Canada. After controlling for the gestational age on the date at which the sample was drawn and maternal weight, MSAFP levels appeared to be approximately 4 to 5% higher in aboriginal women. The possible implications of this finding on an MSAFP screening program are discussed.