Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p- syndrome.

OBJECTIVES: Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques. METHODS: The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients. RESULTS: The results showed 23 pure terminal deletions, one interstitial deletion, one deletion followed by a 3 Mb duplication in 5p, three cases of 5p deletion concomitant to duplications larger than 20 Mb in chromosomes 2, 9, and 18, and one 5p deletion with a chromosome Y deletion. CMA showed relevant CNVs not typically associated with 5p- that may have contributed to the final phenotype in these patients. CONCLUSIONS: The authors have identified three novel rearrangements between chromosomes 5 and 2 (Patient 27), 5 and 18 (Patient 11), and 5 and Y (Patient 22), with breakpoints and overlapped phenotypes that were not previously described. The authors also highlight the need for further molecular investigation using CMA, in different chromosomes beyond chromosome 5 (since those cases did not show only the typical deletion expected for the 5p- syndrome) to explain discordant chromosomal features and overlapped phenotypes to unravel the cause of the syndrome in atypical cases.

Metabolic profiling of organic acids in urine samples of Cri Du Chat syndrome individuals by gas chromatography-mass spectrometry.

Cri Du Chat (CDC) syndrome is a rare genetic condition caused by the deletion of genetic material on the small arm (the p arm) of chromosome 5. A high-pitched cry that sounds like that of a cat, dysmorphic characteristics, and cytogenetic methods are often used for diagnosing the syndrome. In this study, we applied GC-MS analysis for determining organic acids in urine from 17 control volunteers without CDC syndrome, and from 16 individuals with the CDC syndrome in order to determine the profile of organic acids and biochemical pathways alterations resulting from this genetic condition. First, performing multivariate data analysis selected the best method for extracting organic acids with greater signal intensities and good reproducibility. After selection, multivariate (PLS-DA) and univariate (Mann-Whitney test) data analysis discriminated the metabolites responsible for separation between groups. Nine organic acid metabolites had values of VIP ≥ 1.0 and p-values ≤ 0.05, with highest intensities in the samples from CDC individuals, indicating the strongest discriminative power (tricarballylic acid, indoleacetic acid, anthranilic acid, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, 4-hydroxyhippuric acid, pantothenic acid, homovanillic acid, and vanillylmandelic acid). These metabolites are involved in several biochemical pathways like in the tyrosine and phenylalanine metabolism, as well as the tryptophan metabolism, which could be associated (i) to some neuropsychiatric alterations commonly observed in CDC individuals, (ii) to exogenous compounds related to transformation products by intestinal microbial, and (iii) to a possible deficiency in enzyme activity due to the syndrome.

Ebstein anomaly associated with cri du chat (cat's cry) syndrome and 20q duplication.

Ebstein anomaly is a congenital heart defect with a low prevalence and high mortality in the early stages of life. In medical literature, there is no reported association between Ebstein anomaly and cri du chat syndrome. Here, we report the case of a full-term newborn with a low weight for his age and who had a prenatal diagnosis of Ebstein anomaly and a postnatal diagnosis of cri du chat syndrome and 20q duplication detected on array CGH. The patient required medical treatment with inotropic support, high-frequency ventilation and nitric oxide, with an adequate response. Surgical intervention was not needed.

Síndrome de maullido de gato o “Cri Du Chat”: presentación de un caso / Cri-du-chat syndrome: a case report

El presente trabajo se refiere a la deleción del brazo corto del cromosoma 5 responsable del Síndrome de Maullido de Gato o “Cri Du Chat”. Las deleciones son aberraciones cromosómicas no balanceadas y consisten en la perdida de un fragmento de un cromosoma, las mismas pueden ser terminales, intersticiales o en anillo. El efecto fenotípico de la deleción depende del cromosoma implicado y la longitud del segmento delecionado. La apreciación de esta aberración estructural generalmente se dificulta si se trata de deleciones terminales pequeñas o intersticiales. Se tomó una muestra de sangre periférica de un paciente para cultivo linfocitario a petición de médicos de asistencia debido a las características fenotípicas del paciente así como características del llanto y el estridor laríngeo posiblemente asociado acromosomopatías. La muestra se cultivó y procesó según las técnicas estandarizadas en nuestro laboratorio, como resultado del diagnóstico post-natal citogenético se evidenció una deleción terminal del brazo corto del cromosoma 5 en todas las metafases estudiadas (Línea pura) 46XY, del (5), (p15.1).

The following research deals with the missing of the chromosome five's short arm that causes the cry of the cat syndrome or "Cri Du Chat". The missings are unbalanced chromosomic aberrations that consist on the loss of a chromosome's fragment and they could be final, intersticial or in ring. The phenotype effect of the missing depends on the involved chromosome and the length of the missing segment. The assessment of this structural aberration is generally affected when dealing with short final or intersticial missings. A patient's peripheric blood sample was drawn for a lymphocytory culture as the request of assistant doctors due to the patient's phenotypical features, as well as the cry's characteristics and the laringeal whoop associated to chromosomopathies. The sample was processed and cultured according to the standard techniques in our lab. A final missing of the chromosome five's short arm in all the studied meta stages was proved as a result of the cytogenetic post-natal diagnosis.

Síndrome de cri du chat, una rara cromosopatía / Cri du chat syndrome, a rare chromosomal disorder

Antecedentes: El Síndrome de Cri du chat o síndrome de Lejeune, es una enfermedad rara que fue descrita por primera vez en 1963 por Jerome Lejeune, es una cromosomopatía que se caracteriza por un llanto similar al maullido de gato. Se debe a la deleción o supresión parcial o total del material genético en una parte del brazo corto del cromosoma 5. Este síndrome se caracteriza por una variedad de alteraciones físicas y psicomotoras. El análisis cromosómico proporciona el diagnóstico definitivo. Este paciente se presenta como un caso que reúne las características clínicas propias y la alteración cromosómica que caracterizan al síndrome y es el primer caso que se reporta en la literatura Hondureña. Caso clínico: Se presenta el caso de una paciente femenina que presentó llanto similar al maullido de gato en la niñez, con alteraciones físicas y psicomotoras características de este síndrome; por lo que se le realizó estudio citogenético que mostró una deleción terminal del brazo corto del cromosoma 5 (5p) compatible con un Síndrome de Cri du chat. Conclusión: El diagnóstico de esta patología se debe realizar lo mas tempranamente posible para ofrecerles a estos pacientes el manejo multidisciplinario necesario que les permita tener un desarrollo psicomotor y social adecuado...

Síndrome malformativo con retardo mental asociado a un reordenamiento cromosómico / Malformative syndrome with mental retardation associated to a chromosomic rearrangement

El propósito de este trabajo es describir el cuadro clínico y los resultados de la evaluación citogenética de una paciente en la que nuestro grupo ha encontrado un cromosoma anormal derivado de un reordenamiento cromosómico con intercambio de material entre el brazo corto de un cromosoma 5 y el brazo largo de un cromosoma 10. La madre de la paciente, por su parte, resultó tener los dos cromosomas anormales producto del reordenamiento, por lo cual no presenta síntomas. Clínicamente, la paciente mostró retardo mental, baja talla, microcefalia, dismorfias faciales y manos angostas. Los estudios cromosómicos revelaron en la madre una translocación recíproca [46,XX,t(5;10)(p15.3;q24)], y en la hija solamente el cromosoma 5 anormal derivado de la translocación [46,XX,der(5)t(5;10)(p15.3;q24)]. La paciente tiene una trisomía parcial del brazo largo del cromosoma 10, a la cual puede atribuírse el retardo mental y la mayoría de los rasgos físicos que presenta. Asismismo, ella tiene una monosomía parcial del brazo corto del cromosoma 5, que la ausencia de antecedentes del llanto agudo característico de las monosomías 5p con pérdida de las bandas 15.2 y 15.3 (síndrome del maullido) o 15.3 solamente (llanto similar a un maullido) permite suponer como distal a las mismas; ello deberá ser comprobado mediante estudios cromosómicos de alta resolución. Por fin, las referencias a múltiples individuos afectados en esta familia ameritan un estudio genealógico detallado, a fin de perfeccionar la descripción del síndrome, identificar probables portadores sanos y ofrecerles el asesoramiento genético correspondiente. (AU)

Clinical heterogeneity in 80 home-reared children with cri du chat syndrome.

A population of 80 home-reared children with cri du chat syndrome was investigated to document the clinical heterogeneity of the syndrome and to analyze the factors influencing the severity of the phenotypic characteristics. When individuals with isolated deletions were compared with those possessing unbalanced translocations involving other chromosomes in addition to number 5, the latter group had a greater incidence of physical anomalies, more frequent hospitalizations, and a higher mortality. Chronic complaints in both groups included upper respiratory tract infection, otitis media, and a previously unrecognized association with gastrointestinal tract anomalies. In children with terminal deletions, there was a significant negative correlation between the size of the deletion and the individual's intelligence quotient. In addition, patients with larger deletions had more severe growth retardation, particularly with respect to the degree of microcephaly. The gradual progression with age of the characteristic facial features remained consistent regardless of differing racial backgrounds and the size of the deletion. Our findings delineate the variation in the clinical and karyotypic features of this syndrome.