ABSTRACT
Pallister–Killian syndrome (PKS) is a rare genetic developmental disorder characterized, by intellectual disability, seizures, streaks of hypo- or hyperpigmentation and characteristic dysmorphic features. PKS is characterized by the presence of cytogenetic abnormality in form of a supernumerary isochromosome 12p, in a tissue limited mosaicism. The isochromosome 12p is usually not detected in karyotype done from peripheral blood. Presence of patchy pigmentary skin lesions suggest the possibility of mosaicism and karyotype from skin is done which clinches the diagnosis. We describe an infant with severe hypotonia in whom trisomy 12p was detected by chromosomal microarray performed on peripheral blood. The karyotype from blood was normal and combining this information with three copies of 12p in microarray suggests the possibility of tetrasomy12p in mosaic form. The infant did not have any skin patchy pigmentary changes and malformations and hence, the diagnosis of PKS was not clinically suspected. Cytogenetic microarray is the first test for evaluation of cases with developmental delay and intellectual disability, PKS diagnosis may come as a surprise in unsuspected cases without characteristic skin pigmentary abnormality and malformations.
ABSTRACT
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.
Subject(s)
Humans , Female , Child, Preschool , Chromosomes, Human, Pair 12/genetics , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Phenotype , Racial Groups , Karyotyping , MexicoABSTRACT
Pallister-Killian syndrome (PKS) is a rare multisystem disorder characterized by isochromosome 12p and tissue-limited mosaic tetrasomy 12p. In this study, we diagnosed three pediatric patients who were suspicious of having PKS using array-based comparative genomic hybridization (array CGH) and FISH analyses performed on peripheral lymphocytes. Patients 1 and 2 presented with craniofacial dysmorphic features, hypotonia, and a developmental delay. Array CGH revealed two to three copies of 12p in patient 1 and three copies in patient 2. FISH analysis showed trisomy or tetrasomy 12p. Patient 3, who had clinical features comparable to those of patients 1 and 2, was diagnosed by using FISH analysis alone. Here, we report three patients with mosaic tetrasomy 12p. There have been only reported cases diagnosed by chromosome analysis and FISH analysis on skin fibroblast or amniotic fluid. To our knowledge, patient 1 was the first case diagnosed by using array CGH performed on peripheral lymphocytes in Korea.
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Chromosome Disorders/diagnosis , Chromosomes, Human, Pair 12 , Comparative Genomic Hybridization , In Situ Hybridization , TetrasomyABSTRACT
Tetrasomy for the short arm of chromosome 12 (Pallister-Killian syndrome) is an uncommon mosaic aneuploidy, which may present in the prenatal period with an ultrasonographically detected fetal abnormalities or following karyotyping for maternal age and other causes. In this syndrome the chromosome abnormalities, isochromosome is present in amniocyte with a much greater percentage than fetal lymphocyte. The most consistent reported prenatal ultrasound findings for tetrasomy 12p include polyhydramnios with short femurs and a diaphragmatic hernia. We report a case identified by prenatal karyotyping diagnosis.