RESUMEN

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.

Asunto(s)

Discapacidad Intelectual/genética , Anomalías Musculoesqueléticas/genética , Osteocondrodisplasias/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/diagnóstico por imagen , Discapacidad Intelectual/fisiopatología , Masculino , Anomalías Musculoesqueléticas/diagnóstico , Anomalías Musculoesqueléticas/diagnóstico por imagen , Anomalías Musculoesqueléticas/fisiopatología , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/fisiopatología , Radiografía , Secuenciación del Exoma

RESUMEN

Interstitial deletion of chromosome 11 long arm is a rare event. In most of the interstitial deletions on the long arm of chromosome 11 both the position and the size of these deletions are heterogeneous making a precise karyotype-phenotype correlation. In only a few of the reported cases has the deletion been molecularly characterized. Our patient was a 13-year-old male presented; mental motor retardation, strabismus, myopia, retinopathy, sensorineural hearing loss, a long and triangular face, a broad forehead, hypotelorism, nasal septal deviation, a beaked nose, hypoplastic ala nasie, bilateral low-set ears, a high arched palate, crowded teeth, retrognathia, thin lips, a long neck, and sloping shoulders, hyperactive behavior, pulmonary stenosis and lumbar scoliosis. Conventional cytogenetic analysis revealed 46,XY,del(11)(q14.1-q23.3) karyotype in the patient. Array-CGH analysis of the patient's DNA revealed an interstitial deletion encompassing 33.2 Mb in the 11q14.1-q23.3 genomic region (chr11: 83,161,443-116,401,751 ; Hg19). In this report, we present a patient with an interstitial deletion on the long arm of chromosome 11 that encompassed the 11q14.1-q23.3 region; and, using array-CGH analysis, we molecularly characterized the deleted region.

Asunto(s)

Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 11/genética , Discapacidad Intelectual/genética , Adolescente , Análisis Citogenético , Humanos , Masculino

RESUMEN

Isochromosome 18p is a rare chromosomal disorder that occurs with a frequency of approximately one in every 180,000 live births, and affects both genders equally. MOst cases result from a de novo formation. In the literature, there are currently only a small number of reports that describe the phenotypic and clinical features of Isochromosome 18p. In this article, we report six cases that displayed the phenotypic and clinical features of Isochromosome 18p, and which were subsequently confirmed by conventional karyotyping and fluorescence in situ hybridization. We also discuss the clinical features of these patients in the context of the cases previously reported in the literature.

Asunto(s)

Aneuploidia , Trastornos de los Cromosomas , Isocromosomas , Niño , Preescolar , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/patología , Trastornos de los Cromosomas/fisiopatología , Cromosomas Humanos Par 18 , Femenino , Humanos , Lactante , Masculino

RESUMEN

22q11.2 deletion syndrome is a pattern of malformations resulting from abnormalities during cephalic neural crest migration and during the development of the third and fourth branchial arch. It is also known as DiGeorge syndrome, as it is most often associated with a de novo 3 Mb hemizygous 22q11.2 deletion. The recognition of similarities and phenotypic overlap between DiGeorge syndrome and other disorders associated with genetic defects in 22q11 has led to an expanded description of the phenotypic features of this syndrome. Indeed, the extent of this phenotypic variability can often make it difficult to accurately diagnose DiGeorge syndrome. Tertiary monosomy resulting from the 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. In this report, we present a female infant with dysmorphic facial features, microcephaly, a cleft palate, unilateral membranous choanal atresia, convulsions, hypocalcemia, semilobar holoporencephaly and echocardiographic abnormalities. To the best of our knowledge, this is the first description of a newborn displaying both DiGeorge syndrome and deletion 18p syndromes.

Asunto(s)

Deleción Cromosómica , Trastornos de los Cromosomas , Síndrome de DiGeorge , Enfermedades del Recién Nacido , Translocación Genética/genética , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/patología , Trastornos de los Cromosomas/fisiopatología , Cromosomas Humanos Par 18/genética , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/patología , Síndrome de DiGeorge/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/genética , Enfermedades del Recién Nacido/patología , Enfermedades del Recién Nacido/fisiopatología

RESUMEN

Hallermann-Streiff syndrome (HSS) is a genetic disorder characterized by proportionate dwarfism, birdlike facies, hypotrichosis, skin atrophy, dyscephaly, bilateral microphthalmia, congenital cataracts, a narrow, weak, beaked nose, a hypoplastic mandible, and orodental anomalies. Occurrence is sporadic and distinct patterns of inheritance have not been found. This case report describes the dental management of a 3-year-old girl patient with HSS, who had unusual radiographic appearance of teeth. Furthermore, dental treatments and a 30-month follow-up period of the patient with this rare tooth structure malformation have been presented.

Asunto(s)

Dentadura Parcial Removible , Síndrome de Hallermann/complicaciones , Maloclusión/terapia , Preescolar , Femenino , Síndrome de Hallermann/diagnóstico por imagen , Síndrome de Hallermann/terapia , Humanos , Maloclusión/diagnóstico por imagen , Maloclusión/etiología , Radiografía

Asunto(s)

Humanos , Masculino , Preescolar , Inmunoglobulina M/deficiencia , Cromosomas Humanos Par 18/inmunología , Síndromes de Inmunodeficiencia/inmunología , Citometría de Imagen/métodos , Citometría de Imagen/tendencias , Factores Inmunológicos/deficiencia , Aberraciones Cromosómicas , Tonsilectomía/tendencias , Imagen por Resonancia Magnética/métodos , Recurrencia , Infecciones del Sistema Respiratorio/complicaciones

Asunto(s)

Inmunoglobulina M/deficiencia , Cromosomas en Anillo , Preescolar , Cromosomas Humanos Par 18 , Humanos , Masculino

RESUMEN

ARX mutations give rise to both syndromic and nonsyndromic forms of mental retardation (MR). We investigated the most common ARX mutations, c.428_451 dup(24bp) and c.333ins (GCG)7 in a series of 370 mentally retarded FMR1 (CGG)n expansion mutation negative Turkish patients using PCR amplification and high resolution MetaPhor agarose gel electrophoresis. Sequence analysis was also performed for confirmation and discrimination of the mutations. One patient representing non-syndromic X-linked MR showed an abnormal band pattern on agarose gel and sequence analysis of exon 2 of the ARX gene revealed that the patient had the c.428_451 dup(24bp) mutation. When we screened the family members, we found that his sister and mother were also carrier for the same mutation. The proband showed mild MR and subtle clinical findings like dysarthria and lack of fine motor functions. In conclusion, the patients with weak fine motor skills and positive family history for X-linked MR should be screened for the most common ARX gene mutations.

Asunto(s)

Proteínas de Homeodominio/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Mutación/genética , Factores de Transcripción/genética , Adulto , Niño , Análisis Mutacional de ADN , Femenino , Duplicación de Gen/genética , Genotipo , Humanos , Masculino , Linaje , Turquía

RESUMEN

Double partial trisomy resulting from 3:1 segregation of the respective chromosomal segments of the chromosomes involved in a balanced translocation in meiosis is rarely reported in the literature. We present here a first patient with multiple congenital malformations associated with double partial trisomy of 10pter-p15 and 14pter-q13 resulting from 3:1 segregation of maternal balanced translocation t(10;14)(p15;q13). Proximal partial trisomy of chromosome 14 and subterminal trisomy of the short arm of the chromosome 10 are rare. The present case is the first case with double partial trisomy of these segments resulting from 3:1 segregation of a maternal balanced translocation.

Asunto(s)

Anomalías Múltiples/genética , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 14/genética , Translocación Genética/genética , Trisomía/genética , Adulto , Cromosomas Humanos 6-12 y X , Salud de la Familia , Femenino , Humanos , Lactante , Masculino

RESUMEN

We report, a newborn presenting multiple congenital abnormalities with karyotype; 47,XY,der(7)t(6;7)(pter-p23::p15-->qter),+der(9)t(7;9)(pter-->p15::q21.2--> pter)t(6;7;9)(p23;p15;q21.2)mat[20]. The mother and her phenotypically normal daughter were carriers of a complex chromosomal rearrangement with karyotypes; 46,XX,t(6;7;9)(p23;p15;q21.2)[20]. Paternal chromosomes were normal. In our case the extra derivative chromosome was the result of a 4:2 segregation of the chromosomes involved in translocation during oogenesis. Double partial trisomy in newborns resulting from 4:2 segregation is a rare event, and double partial trisomies of the 6p23-pter and trisomy 9pter-q22 regions have not reported to date.

Asunto(s)

Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos 6-12 y X/genética , Translocación Genética , Trisomía/genética , Anomalías Múltiples/diagnóstico , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Cariotipo , Cariotipificación , Masculino

RESUMEN

Pallister-Killian syndrome (PKS) is a rare genetic disorder usually characterized by mosaic tetrasomy of isochromosome 12p detected in cultured fibroblast cells. We describe here a patient with PKS and intrachromosomal triplication of the short arm of chromosome 12. Her karyotype was mos 46,XX,inv trp(12)(p11.2p13)[34]/ 46,XX[16]de novo by conventional cytogenetics and fluorescent in situ hybridization (FISH) analysis. However, this chromosomal abnormality was not detected from the patient's cultured blood lymphocytes. We report here the third patient with intrachromosomal triplication on the short arm of chromosome 12, presenting a PKS phenotype.

Asunto(s)

Anomalías Múltiples/genética , Atresia de las Coanas/genética , Deleción Cromosómica , Cromosomas Humanos Par 13 , Cisterna Magna/anomalías , Humanos , Lactante , Masculino

RESUMEN

We report here a prenatal case with de novo supernumerary marker chromosome originating from chromosome 17 in non-mosaic form resulting in normal pregnancy outcome. In this case, a 26-year-old pregnant woman was referred for amniocenthesis and microdeletion Fluorescence In Situ Hybridization (FISH) testing at 18 weeks of gestation due to history of a previous child with Angelman Syndrome. PWS/AS region deletion was excluded by FISH. A de novo supernumerary, non-satellited, monocentric marker chromosome was detected during conventional cytogenetic analysis. With the use of FISH testing, it was found that the marker chromosome originated from chromosome 17. Additionally, the marker chromosome was found not to contain the Smith-Magenis and Miller Dieker syndrome regions. After detailed review of the literature, genetic counseling was given to the family, and the family decided to continue the pregnancy to term. A female child was born at term without any phenotypical abnormalities and clinical complications. Follow-up at 15 months-of-age revealed no developmental abnormalities. To our knowledge, our patient is the first reported prenatal case with a de novo monocentric, supernumerary marker chromosome derived from chromosome 17 in a non-mosaic form that resulting in normal pregnancy outcome.

Asunto(s)

Amniocentesis , Aberraciones Cromosómicas , Cromosomas Humanos Par 17/genética , Adulto , Bandeo Cromosómico , Hibridación Genómica Comparativa , Femenino , Estudios de Seguimiento , Asesoramiento Genético , Humanos , Hibridación Fluorescente in Situ , Lactante , Recién Nacido , Embarazo

RESUMEN

AIMS: The deleterious nature of peripheral arterial disease (PAD) is compounded by a status of underdiagnosed and undertreated disease. We evaluated the prevalence and predictive factors of PAD in high-risk patients using the ankle-brachial index (ABI). METHODS: The ABI was measured by general practitioners in France (May 2005-February 2006) in 5679 adults aged 55 years or older and considered at high risk. The primary outcome was prevalence of PAD (ABI strictly below 0.90). RESULTS: In all, 21.3% patients had signs or symptoms suggestive of PAD, 42.1% had previous history of atherothrombotic disease and 36.6% had two or more cardiovascular risk factors. Prevalence of PAD was 27.8% overall, ranging from 10.4% in patients with cardiovascular risk factors only to approximately 38% in each other subgroup. Prevalence differed depending on the localization of atherothrombotic events: it was 57.1-75.0% in patients with past history of symptomatic PAD; 24.6-31.1% in those who had experienced cerebrovascular and/or coronary events. Regarding the classical cardiovascular risk factors, PAD was more frequent when smoking and hypercholesterolemia history were reported. PAD prevalence was also higher in patients with history of abdominal aortic aneurysm, renal hypertension or atherothrombotic event. Intermittent claudication, lack of one pulse in the lower limbs, smoking, diabetes and renovascular hypertension were the main factors predictive of low ABI. CONCLUSIONS: Given the elevated prevalence of PAD in high-risk patients and easiness of diagnosis using ABI in primary care, undoubtedly better awareness would help preserve individual cardiovascular health and achieve public health goals.

Asunto(s)

Índice Tobillo Braquial , Enfermedades Cardiovasculares/prevención & control , Enfermedades Vasculares Periféricas/diagnóstico , Anciano , Enfermedades Cardiovasculares/epidemiología , Métodos Epidemiológicos , Medicina Familiar y Comunitaria , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/epidemiología , Prevalencia , Factores de Riesgo

RESUMEN

We report here the first Turkish patient with progressive symmetric erythrokeratoderma. The patient's skin lesions appeared in the axillae at 3 months of age, and gradually spread to other flexural areas and to the trunk. Dermatological examination of the boy at 3.5 years of age revealed symmetric, hyperkeratotic plaques with erythematous outlines on the neck, wrists, armpits, trunk and posterior knees. The histopathological changes were nonspecific, including marked hyperkeratosis, irregular acanthosis, focal papillomatosis and perivascular lymphocytic infiltrates. Molecular studies of the loricrin (LOR), connexin 31 (GJB3) and connexin 30.3 (GJB4) genes did not identify a disease-causing mutation. These results further underline the genetic heterogeneity of the erythrokeratodermas.

Asunto(s)

Eritema/genética , Hiperqueratosis Epidermolítica/genética , Mutación/genética , Preescolar , Conexinas/genética , Consanguinidad , Diagnóstico Diferencial , Eritema/patología , Heterogeneidad Genética , Humanos , Hiperqueratosis Epidermolítica/patología , Masculino , Proteínas de la Membrana/genética , Linaje

RESUMEN

BACKGROUND: The interaction between the use of percutaneous coronary intervention (PCI) for non-ST-elevation acute coronary syndromes and the use of secondary prevention medications was analysed in the French S-Témoin Registry. METHODS: The population consisted of 2433 patients seen by their cardiologists at an outpatient clinic 2-12 months after non ST-elevation ACS; the survey was carried out from September 2004 to April 2005. RESULTS: Overall, patients undergoing PCI (75% of the population) had higher levels of prescription of recommended secondary prevention medications. Multivariate logistic regression analysis showed that the use and type of coronary intervention (drug eluting versus bare metal stents) was an independent correlate of the use of dual antiplatelet therapy. In addition, time from the acute episode was also a strong correlate of dual antiplatelet therapy. Statins were also more often used in patients with PCI. CONCLUSION: Patients not treated with PCI are less likely to receive appropriate secondary prevention medications after non ST-elevation acute coronary syndromes. Specific efforts should be directed towards these patients, in particular as regards the prescription of dual antiplatelet therapy.

Asunto(s)

Angioplastia Coronaria con Balón , Fármacos Cardiovasculares/uso terapéutico , Infarto del Miocardio/terapia , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Angina Inestable/prevención & control , Angina Inestable/terapia , Bloqueadores de los Canales de Calcio/uso terapéutico , Quimioprevención , Prescripciones de Medicamentos , Femenino , Estudios de Seguimiento , Francia , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/uso terapéutico , Sistema de Registros , Stents , Síndrome

RESUMEN

OBJECTIVES: We evaluated time and spectral analyses of 24-h heart rate variability (HRV) and the heart rate responses to passive tilt in patients with idiopathic Parkinson's disease (IPD) in order to investigate cardiovascular autonomic functions. MATERIAL AND METHODS: Twenty-three subjects with IPD without autonomic symptoms and 15 age-matched healthy controls were enrolled. Frequency- and time-domain HRV parameters were studied during resting and passive head-up tilt (HUT) test. RESULTS: All time-domain parameters were found to be low in patients with IPD. In patients with IPD, both low frequency (LF) and high frequency (HF) decreased during HUT period and no significant change in LF to HF ratio was noted. Both time- and frequency-domain HRV indices showed no correlation with age, disease severity and duration, and with l-dopa medication. CONCLUSION: The results indicate that impairment of autonomic nervous system function in IPD without autonomic symptoms is frequent, and does not show clear association with clinical stage and the age of the patients.

Asunto(s)

Frecuencia Cardíaca/fisiología , Enfermedad de Parkinson/fisiopatología , Factores de Edad , Antiparkinsonianos/administración & dosificación , Sistema Nervioso Autónomo/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Levodopa/administración & dosificación , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Pruebas de Mesa Inclinada , Factores de Tiempo

RESUMEN

Until recently, presence of de novo marker or derivative chromosomes was quite problematic for genetic counseling especially in prenatal diagnosis, because characterization of marker and derivative chromosomes by conventional cytogenetic techniques was nearly impossible. However, recently developed molecular cytogenetic technique named Multicolor Fluorescence in Situ Hybridization (M-FISH) which paints all human chromosomes in 24 different colors allows us to characterize marker and derivative chromosomes in a single hybridization. In this study, we applied M-FISH to determine the origin of 3 marker and 3 derivative chromosomes. Marker chromosomes were found to originate from chromosome 15 in two postnatal and one prenatal case. Of these, one of the postnatal cases displayed clinical findings of inv dup (115) syndrome and the other of infertility, and the prenatal case went through amniocentesis due to the triple test results. Karyotypes of the patients with derivative chromosomes were designated as 46,XY,der (21)t(1;21)(q32;p11), 46,XX,der(8)t(8;9)(p23;p22) and 46,XX,der(18)t(18;20)(q32;p11.2) according to cytogenetic and M-FISH studies. All of the M-FISH results were confirmed with locus specific or whole chromosome painting probes. The case with der (8)t(8;9) had trisomy 9(p22-pter) and monosomy 8(p23-pter) due to this derivative chromosome. The case with der(18)t(18;20) had trisomy 20(p11.2-pter) and monosomy 18(q32-qter). Parental origins of the derivative chromosomes were analyzed using microsatellite markers located in the trisomic chromosomal segments. Patients' clinical findings were compared with the literature.

Asunto(s)

Hibridación Fluorescente in Situ/métodos , Trisomía/genética , Adulto , Preescolar , Cromosomas Humanos Par 15/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 20/genética , Cromosomas Humanos Par 8/genética , Cromosomas Humanos Par 9/genética , Citogenética , Femenino , Humanos , Lactante , Cariotipificación , Masculino , Padres

RESUMEN

Subtelomeric chromosomal rearrangements detected in patients with idiopathic mental retardation and dysmorphic features: Cryptic aberrations involving the subtelomeric regions of chromosomes are thought to be responsible for idiopathic mental retardation (MR) and multiple congenital anomalies, although the exact incidence of these aberrations is still unclear. With the advent of chromosome-specific telomeric Fluorescence In Situ Hybridization (FISH) probes, it is now possible to identify submicroscopic rearrangements of distal ends of the chromosomes that can not be detected by conventional cytogenetic methods. In this study, cryptic subtelomeric chromosomal aberrations were detected in two of ten patients with idiopathic MR and dysmorphic features by using FISH probes of subtelomeric regions of all chromosome arms. A cryptic unbalanced de novo translocation was detected between the subtelomeric regions of the chromosome 10p and 18p in a patient with severe mental retardation, sensorineuronal deafness and several dysmorphic features. In the other patient, with mild mental retardation and dysmorphic features, a de novo subtelomeric deletion of chromosome 2q was found. In conclusion, in both familial and sporadic cases with idiopathic MR and dysmorphic features, the detection of chromosomal aberrations including subtelomeric rearrangements is of great importance in offering genetic counseling and prenatal diagnosis.

Asunto(s)

Aberraciones Cromosómicas , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 18 , Anomalías Craneofaciales/genética , Reordenamiento Génico/genética , Discapacidad Intelectual/genética , Telómero/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Niño , Preescolar , Bandeo Cromosómico , Deleción Cromosómica , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 18/genética , Cromosomas Humanos Par 2 , Anomalías Craneofaciales/diagnóstico , Sordera/genética , Dermoscopía , Femenino , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , Persona de Mediana Edad , Translocación Genética/genética

RESUMEN

A case with de novo interstitial deletion of chromosome 7q21.1-q22: A patient with multiple congenital anomalies was found to have a de novo proximal interstitial deletion of chromosome 7q21.1-q22. The patient was 10.5 years of age, and manifestations include growth retardation (below 3rd percentile), mental retardation, mild microcephaly, hypersensitivity to noise, mild spasticity, short palpebral fissures, alternant exotropia, compensated hypermetropic astigmatism, hypotelorism, hypoplastic labia majora and minora, clinodactyly of fingers 4 and 5. Molecular studies revealed that the deletion had a paternal origin, while chromosomes of both parents cytogenetically were shown to be normal. Molecular, and fluorescence in situ hybridization (FISH) analyses confirmed no deletion at the Williams-Beuren Syndrome region. Some of the heterogeneous clinical findings were consistent with previously reported cases of same chromosomal breakpoints.

Asunto(s)

Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 7/genética , Discapacidades del Desarrollo/genética , Genitales Femeninos/anomalías , Anomalías Múltiples/diagnóstico , Baclofeno , Niño , Rotura Cromosómica , Discapacidades del Desarrollo/diagnóstico , Femenino , Humanos , Hibridación Fluorescente in Situ