Síndrome de Pallister-Killian en una paciente mestiza mexicana: Reporte de caso / Paüister-KiUian syndrome in a Mexican mestizo patient: Case report

El síndrome de Pallister-Killian es una entidad poco frecuente causada por tetrasomía 12p en mosaico. Presenta facies tosca, alopecia frontotemporal, frente prominente, fisuras palpebrales oblicuas ascendentes, hipertelorismo ocular, ptosis palpebral, estrabismo, epicanto, puente nasal ancho, nariz corta, narinas antevertidas, filtrum largo, labio superior delgado e inferior prominente, pabellones auriculares con lóbulos gruesos y protruidos, cuello corto, pezones supernumerarios, manos anchas, braquidactilia, alteraciones en la pigmentación de la piel, cardiopatía congénita, discapacidad intelectual y crisis convulsivas. Su diagnóstico es complejo, ya que, en sangre periférica, el cariotipo suele ser normal. Se presenta el caso de una paciente mestiza mexicana de 4 años de edad con retraso en el desarrollo psicomotor y características fenotípicas que correspondieron a síndrome de Pallister-Killian. El cariotipo en fibroblastos de la biopsia de piel demostró mos47,XX,i(12)(p10)--#91;85--#93;/46,XX--#91;21--#93;. Un equipo multidisciplinario realiza el seguimiento con controles regulares por los departamentos de Neurología, Pediatría General y Genética Médica.

Pallister-Killian syndrome is caused by a tetrasomy 12p mosaicism and is characterized by facial dysmorphism, pigmentary skin anomalies, congenital heart defects, diaphragmatic hernia, epilepsy and mental retardation. The diagnosis is complex as the cytogenetic analysis in blood is usually normal, requiring karyotyping in other tissues, therefore the clinical suspicion is critical to guide the diagnostic tests and the patient requires an interdisciplinary clinical evaluation regarding the several manifestation of the syndrome. W e present the case of a Mexican mestizo female patient of 4 years of age referred by psychomotor delay and cleft palate; the clinical multidisciplinary evaluation demonstrated characteristics corresponding to the Pallister-Killian syndrome. The GTG banding karyotype analysis was normal, the skin fibroblast was mos47,XX,i(12)(p10)--#91;85--#93;/46,XX--#91;21--#93;. This case is an example of the importance of the clinical evaluation in order to establish a diagnosis that is a challenge for the clinical multidisciplinary team to offer medical management and genetic counseling.

[Pallister-Killian syndrome in a Mexican mestizo patient. Case report]. / Síndrome de Pallister-Killian en una paciente mestiza mexicana. Reporte de caso.

Pallister-Killian syndrome is caused by a tetrasomy 12p mosaicism and is characterized by facial dysmorphism, pigmentary skin anomalies, congenital heart defects, diaphragmatic hernia, epilepsy and mental retardation. The diagnosis is complex as the cytogenetic analysis in blood is usually normal, requiring karyotyping in other tissues, therefore the clinical suspicion is critical to guide the diagnostic tests and the patient requires an interdisciplinary clinical evaluation regarding the several manifestation of the syndrome. W e present the case of a Mexican mestizo female patient of 4 years of age referred by psychomotor delay and cleft palate; the clinical multidisciplinary evaluation demonstrated characteristics corresponding to the Pallister-Killian syndrome. The GTG banding karyotype analysis was normal, the skin fibroblast was mos47,XX,i(12)(p10)[85]/46,XX[21]. This case is an example of the importance of the clinical evaluation in order to establish a diagnosis that is a challenge for the clinical multidisciplinary team to offer medical management and genetic counseling.

El síndrome de Pallister-Killian es una entidad poco frecuente causada por tetrasomía 12p en mosaico. Presenta facies tosca, alopecia frontotemporal, frente prominente, fisuras palpebrales oblicuas ascendentes, hipertelorismo ocular, ptosis palpebral, estrabismo, epicanto, puente nasal ancho, nariz corta, narinas antevertidas, filtrum largo, labio superior delgado e inferior prominente, pabellones auriculares con lóbulos gruesos y protruidos, cuello corto, pezones supernumerarios, manos anchas, braquidactilia, alteraciones en la pigmentación de la piel, cardiopatía congénita, discapacidad intelectual y crisis convulsivas. Su diagnóstico es complejo, ya que, en sangre periférica, el cariotipo suele ser normal. Se presenta el caso de una paciente mestiza mexicana de 4 años de edad con retraso en el desarrollo psicomotor y características fenotípicas que correspondieron a síndrome de Pallister-Killian. El cariotipo en fibroblastos de la biopsia de piel demostró mos47,XX,i(12)(p10)[85]/46,XX[21]. Un equipo multidisciplinario realiza el seguimiento con controles regulares por los departamentos de Neurología, Pediatría General y Genética Médica.

Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease.

INTRODUCTION: Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. OBJECTIVES: We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. MATERIAL AND METHODS: The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. RESULTS: A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. DISCUSSION: While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral.

Importancia del diagnóstico de mutaciones en el gen de la conexina 26 en el manejo integral de la sordera congénita no sindrómica / Importance of the diagnosis of connexin 26 gene mutations in the integral management of non-syndromic congenital deafness

Introducción. La sordera congénita es un problema de salud pública. Su incidencia en México es de 2-3 por cada 1000 recién nacidos. El diagnóstico oportuno con el tamiz auditivo neonatal es fundamental para un mejor pronóstico funcional. Aproximadamente 70% de las sorderas congénitas son de origen genético, con herencia autosómica recesiva. La mayoría de estos casos se asocia con mutaciones en el gen GJB2 , que codifica para la proteína conexina 26. Hay tres mutaciones reportadas como las más frecuentes en este gen: c.35delG, c.167delT y c.235delC. Métodos. Previo consentimiento informado de los pacientes, se obtuvo 1 ml de sangre periférica para la extracción de ADN. Mediante las técnicas de PCR-RFLP o PCR seguida de secuenciación, se buscaron las tres mutaciones más frecuentes del gen GJB2 . Resultados. Se realizó el estudio molecular en 11 pacientes: Se encontró un cambio en la secuencia codificante en cinco de ellos. Un paciente fue homocigoto para c.35delG; otro resultó heterocigoto para c.35insG, mutación no reportada previamente; un tercero fue heterocigoto para c.34G>T y dos más fueron heterocigotos para el polimorfismo c.79G>A (p.V27I). En ningún caso se hallaron las mutaciones c.167delT y c.235delC. Conclusiones. Se encontraron cambios de secuencias que correspondieron a dos polimorfismos y a tres mutaciones. La frecuencia de las tres mutaciones investigadas fue menor a lo reportado en la literatura y se encontró una mutación no reportada previamente. Este estudio evidencia la importancia del diagnóstico oportuno con manejo integral, incluyendo el asesoramiento genético con base en estudios moleculares, y resalta la importancia de conocer el perfil genotípico de este grupo de pacientes.

Background. Congenital deafness is a public health problem affecting 2-3:1000 newborns in Mexico. Neonatal audiologic screening allows early detection with important implications for the functional prognosis. About 70% of cases of congenital deafness are associated with a genetic etiology with an autosomal recessive pattern of inheritance. Most cases are caused by mutations in the GJB2 gene, which codifies conexin 26. The three most commonly reported mutations in this gene are c.35delG, c.167delT and c.235delC. Methods. After obtaining informed consent, DNA was extracted from a blood sample, and the three previously mentioned mutations were searched for using PCR-RFLP or PCR followed by sequencing. Results. Molecular analysis was carried out in 11 patients. In five of these patients, a change in sequence was observed. In none of the patients were c.167delT and c.235delC mutations found. One patient was homozygous for c.35delG and another patient was heterozygous for c.35insG, which is a mutation not previously reported. A third patient was heterozygous for c.34G>T. Two additional patients had the c.79G>A (p.V27I) polymorphism. Conclusions. Frequency of the three mutations analyzed was lower compared to other populations. Five sequence changes were observed, two polymorphisms and three mutations, one of them novel. This study also demonstrates the relevance of early diagnosis and multidisciplinary management and the importance of determining the genetic basis of this disease in pediatric patients with congenital deafness.