Pallister-Killian syndrome (PKS) is a rare multiple congenital anomaly/intellectual deficit syndrome caused by mosaic tissue-limited tetrasomy for chromosome 12p. Incidence is uncertain and is estimated around 1/25,000. A number of cases are prenatally diagnosed because of abnormal ultrasonic findings, and abnormal presentation at birth is usual. Most common signs include facial dysmorphism, rhizomelic limb shortness, small hands and feet with nail hypoplasia. Craniofacial manifestations include a ``coarse'' face with flat profile, high forehead with temporo-frontal balding, sparseness of eyebrows and lashes, shallow supraorbital ridges, upslanting palpebral fissures, hypertelorism, flat and broad nasal bridge, short nose with upturned nares, large mouth with downturned corners and prominent upper lip. Macroglossia and pointed chin occur with age. Hypotonia is present at birth with contractures developing with age. A wide range of congenital malformations may be present, the most specific being diaphragmatic and anal defects. Heart defects, mainly ventricular septal defects, are present in 25% of cases. Severe intellectual deficit, pigmentary skin anomalies, deafness and seizures are frequent signs. Patients with PKS have mosaïcism for a supernumerary isochromosome 12p, resulting in four copies of the short arm of chromosome 12 instead of the normal two. All reported cases of this disorder have been sporadic. The isochromosome is mostly of maternal origin. Selection against i(12p) cells is observed in vitro, and probably also occur in vivo. Karyotype is 47, XX or XY, i(12)(p10)/ 46,XX or XY. Clinical recognition is very important as the additional chromosome is usually absent from routine blood lymphocytes examination. Cytogenetic diagnosis requires skin biopsy and fibroblast chromosome examination. The isochromosome is usually present in 30-100% of fibroblast metaphases. In situ hybridization with chromosome 12-specific DNA probes can be used to confirm the chromosome identity. Interphase FISH on a buccal smear may allow a fast preliminary diagnosis. Differential diagnoses include trisomy 12p and Fryns syndrome (see these terms). Antenatal diagnosis may be possible through ultrasound examination revealing abnormal findings such as diaphragmatic hernia, polyhydramnios, hydrops fetalis, cardiac malformations, short limbs, and other, leading to amniocentesis and chromosomal diagnosis. Antenatal diagnosis is also possible after choriocentesis for maternal age. There is no specific therapy. Affected children may benefit from early intervention programs and special education. Prognosis is usually poor. Death may occur perinatally, mainly due to diaphragmatic hernias, or during the first years of life in about a half of patients. Intellectual deficit is mostly profound and almost always accompanied with seizures. The manifestations (facial dysmorphism and malformations) progress with age. Some patients with a low level mosaïcism are less severely affected.
Last update: January 2009