Clinical and cytogenetic characterization of a patient with tetrasomy 18p / Caracterización clínica y citogenética de un paciente con tetrasomía 18p

The 18p tetrasomy is a structural chromosomal abnormality with the presence of an extra isochromosome 18p, caused by a nondisjunction failure during maternal meiosis II. This additional i(18p) occurs in 1 of 180,000 live-born children worldwide, affecting males and females equally. It is characterized by craniofacial dysmorphisms; ears, nose and throat (ENT) abnormalities; musculoskeletal alterations; and global development delay. We aim to present the clinical and cytogenetic findings of a 3-year-10-month-old Latin American male with i(18p), to support the gene dosage effects, comparing his features with the ones reported in literature. This patient was product of the second pregnancy of a 39-year-old woman and the first son of a 49-year-old man. His main clinical features were microcephaly, facial dysmorphism, generalized hypotonia, and developmental delay. A blood sample of the patient was required to perform a GTG-banded karyotype and a fluorescence in situ hybridization (FISH) for chromosome 18 short arm. In addition, an SNP microarray analysis was carried out to detect genomic imbalances. Cytogenetic analysis revealed the presence of a metacentric supernumerary marker chromosome. The FISH study confirmed the origin of the marker chromosome by showing two signals for the 18p subtelomere and an intermediate signal for the 18 centromere. The microarray analysis showed a copy number gain of 18,385 Mb within the 18p.Tetrasomy tends to be a result of de novo events. The presence of the patient's isochromosome could be explained by advanced maternal age as it is known that this factor has high influence in isochromosome formation. Despite that there were no genes associated with the i(18p)'s clinical manifestations, these features are negatively correlated with dosage effects of the entire short arm. Physical and language therapy was recommended to the patient; the family received medical orientation, and awareness in family planning was raised.

La tetrasomía 18p es una anormalidad cromosómica estructural con la presencia de un isocromosoma extra 18p, causado por una no disyunción durante la meiosis materna II. Este adicional i(18p) ocurre en 1 de 180.000 niños nacidos vivos en todo el mundo, y afecta a hombres y mujeres por igual. Se caracteriza por dismorfias craneofaciales; anomalías en oídos, nariz y garganta (ENT); alteraciones musculoesqueléticas y del desarrollo global. Nuestro objetivo es presentar los hallazgos clínicos y citogenéticos de un varón latinoamericano de 3 años y 10 meses de edad con i(18p), para explicar los efectos de dosificación génica, comparando sus características con las reportadas en la literatura. Este paciente es producto del segundo embarazo de una mujer de 39 años y el primer hijo de un hombre de 49 años. Sus principales características clínicas fueron microcefalia, dismorfia facial, hipotonía generalizada y retraso global en el desarrollo. Se requirió una muestra de sangre del paciente para realizar un cariotipo con bandas GTG y una hibridación fluorescente in situ (FISH) para el análisis del brazo corto del cromosoma 18. Además, se llevó a cabo un análisis de microarreglos para detectar desequilibrios genómicos. El análisis citogenético reveló la presencia de un cromosoma supernumerario metacéntrico. Mientras que el estudio FISH confirma el origen del cromosoma marcador al mostrar dos señales para subtelómeros 18p y una señal intermedia para el centrómero 18. El análisis de microarreglos mostró una ganancia en el número de copias de 18,385 Mb dentro de la región 18p.La tetrasomía tiende a ser el resultado de eventos de novo. El isocromosoma del paciente podría explicarse por la edad materna avanzada, ya que se sabe que tiene una gran influencia en su formación. A pesar de que no hay genes asociados con las manifestaciones clínicas de i(18p), estas características están negativamente correlacionadas con los efectos de dosificación de todo el brazo corto. Se le recomendó terapia física y de lenguaje al paciente, la familia recibió orientación médica y se concientiza sobre la planificación familiar.

Prenatal diagnosis of trisomy 21 without the Down syndrome phenotype.

OBJECTIVE: To report a patient with the prenatal diagnosis of trisomy 21 without the clinical Down syndrome (DS) phenotype secondary to the absence of the Down syndrome chromosomal region (DSCR) in a derivative chromosome 21. CASE REPORT AND METHODS: A newborn patient with prenatal diagnosis of duodenal atresia. Cytogenetic studies revealed a regular trisomy 21. At birth, she did not present the clinical features of DS. FISH analysis was performed in the patient with the LSI spectrum probe for the DSCR and in the mother with FISH multicolor analysis using painting probes for chromosomes 20 and 21. RESULTS: FISH analysis in the patient showed two hybridization signals suggesting that the third chromosome 21 did not have the DSCR region explaining the absence of the DS phenotype. FISH multicolor analysis in the mother showed three hybridization signals for chromosomes 20 and 21, concluding a maternal karyotype, 46,XX,t(20;21)(p11.2;q22.1). CONCLUSIONS: The patient was found to have a derivative chromosome 21 secondary to a nondisjunction error in meiosis II without the DS critical region and the phenotype was mostly secondary to the combination of the two partial trisomies.

Facial anthropometric measurements in offspring of epileptic mothers.

BACKGROUND: Minor facial anomalies in 14-33% of exposed fetuses have been associated with the teratogenic effect of antiepileptic drugs (AED) since 1968. The purpose of this article is to describe the facial characteristics of offspring of epileptic mothers with and without exposure to AED by means of 22 anthropometric measurements, for the purpose of comparison with the measurements of offspring of non-epileptic women previously described in the literature, and to correlate the facial anomalies with the specific drug. METHODS: An interval was defined where 95% of the central values were considered as "common values" and the remaining 5% as "uncommon values" (UV) or as being in the "alert zone"; the odds ratio with Wolf modification was used and then Fisher's test for comparison with healthy newborns. Full-term eutrophic newborns of epileptic mothers who received attention at the epilepsy clinic of a gyneco-obstetric center were included. RESULTS: During the study period, 72 eutrophic, full-term newborns were included; in 70 cases at least one measurement was found in the alert zone, with a predominance of the mid-line area. No differences were found between neonates who received monotherapy vs. polytherapy. The groups exposed to phenobarbital, clonazepam and multiple AED showed more uncommon values (p < 0.05), identified as minor dysmorphisms by other authors. It seems to be a particular susceptibility of the mid-line of the face to show the effects of AED and, additionally, of environmental agents. CONCLUSIONS: No differences were found in the facial values among the different AED used in monotherapy form. It is suggested that the choice of drug used during pregnancy must be decided on according to the clinical diagnosis of each mother's epilepsy, and not on the basis of potential teratogenic risk.

[Abnormalities of sex chromosomes and relationship with reproduction disorders]. / Alteraciones de los sexocromosomas y su relación con los trastornos de la reproducción.

One third of the reproductive failure with genetic aetiology are explained by chromosomal rearrangements; the purpose of the study was to find the frequency of sex chromosome anomalies in Mexican population with amenorrhea, sterility or infertility at the National Institute of Perinatology. We realized cytogenetic studies at the Genetics' laboratory in blood samples from 1st january 1984 to 31st December 1995, with the next indications: amenorrhea, sterility, infertility and history of congenital defects that suggest chromosomal anomalies and correlated with the clinical findings. From 3,201 cytogenetic studies we performed in peripheral blood samples, we detected: 61 patients with anomalies of the sex chromosomes predominantly mosaics. We found sex chromosome rearrangements in 1.5% of the patients studied, so it's important to consider this aetiology in the study of infertility and sterility.

[Attitude to and acceptance of prenatal cytogenetic diagnosis by pregnant women]. / Actitud y aceptación de las mujeres embarazadas hacia el diagnóstico citogenético prenatal.

Methods for cytogenetic prenatal diagnosis available in México require from women to accept the risk of procedures and to take a decision in the case of an abnormal result. We applied a questionnaire to 264 pregnant women from August 1990 to July 1991 with the purpose of describing the characteristics of these women and the factors involved in making the decision. Two hundred and nine patients (79%) accepted the procedures. The acceptance was related with a high level of studies and inversely related to their religious beliefs. The interviewer did not influence the decision; but it was important to have previous information about the procedures. Those women with the highest social, financial, and study level and those who did not practice their religion accepted the possibility of an abortion.