Aliases: Mosaic Tetrasomy 12p, Isochromosome 12p Syndrome, Teschler-Nicola-Killian Syndrome
Gene(s) involved: Genes in the critical region of chromosome 12p.
Brief description of disorder: Pallister-Killian Syndrome (PKS) is a tissue-limited mosaic condition characterized by hypotonia, developmental delay, delayed or absent speech, a characteristic hair pattern, streaks of hypo- or hyper-pigmented skin, and a distinctive facial gestalt. Facial features include a high, prominent forehead, hypertelorism, epicanthal folds, upward slanting palpebral fissures, broad nasal bridge, coarse facial features, low-set ears, short neck, and large mouth. Other associated characteristics of this disorder include seizures, diaphragmatic hernia, sensorineural hearing loss, short arms and legs, and a high arched or cleft palate. Congenital heart defects, accessory nipples, cryptorchidism, and feeding difficulties have also been reported.
The prevalence of PKS is unknown, with little more than 30 reported cases worldwide.
Inheritance pattern: PKS is the result of a nondisjunction event in maternal meiosis. Cases are sporadic.
Genetics: Pallister-Killian syndrome is caused by tetrasomy 12p, arising from a metacentric chromosome composed of two identical copies of the short arm of chromosome 12, known as an isochromosome (i(12p)). Tetrasomy 12p is a tissue-limited mosaic condition in which lymphocytes exhibit a normal karyotype and fibroblasts exhibit the characteristic 47 chromosomes. There have been reports of low levels of tetrasomy 12p detectable in blood. Conventional cytogenetic analysis, FISH, and aCGH can all detect tetrasomy 12p; however the frequency of detection is dependent upon the level of mosaicism and the type of tissue sample.
Test method: Conventional G-banded cytogenetic analysis, FISH, and array on cultured fibroblasts.
Test sensitivity: Cytogenetic analysis on cultured fibroblasts detects nearly all cases of tetrasomy 12p. FISH and array will detect 98-100% of deletions/ duplications. Mutation analysis is not appropriate or necessary for this diagnosis.
Specimen requirements for cytogenetic analysis, FISH, or Array:
Skin Biopsy: 1-3mm (minimum)
Blood is generally not an accepted tissue for this diagnostic test.
Turn-around-time: 7-14 days
References:
Revised 6-3-2011
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