These defects include: brain atrophy, agenesis of the corpus callosum, polymicrogyria of the brain, and/or spot calcifications in the brain's lateral sulcus; deafness and/or blindness; autonomic nervous system dysfunctions such as anhidrosis, hypohidrosis, and/or episodic spells of hyperventilation interspersed with breath-holding; symptoms of spinal cord malformations; profound or less commonly mild to severe intellectual disability; epileptic seizures; heart and/or anal defects; diaphragmatic hernias; marked muscle weakness; supernumerary nipples; abnormal facial features such as frontal bossing, high frontal hairline, balding around the temple and frontal areas, sparse eyebrows and lashes, hypertelorism, small and flat nose, full cheeks, long philtrum, large mouth with downturned corners, thin cupid's bow-shaped upper lip, micrognathia (i.e. undersized jaw), disformed ears that are low-set, thick eyebrows, and/or prominent lips and chin; abnormal oral/dental features such as enlarged tongue, overgrowth of the alveolar ridge and/or gums, delayed teeth eruption, and/or missing or double teeth; patchy skin depigmentations; skeletal anomalies such as limb shortening, lymphedema, increased soft tissues in the extremities, short/broad palms and/or fingers, and/or clinodactyly of the fifth fingers or toes; excessive prenatal and birth weights followed by postnatal declines in growth rates; delayed closure of the anterior fontanel; and/or delayed puberty in males but not females.
[1][3] Recent studies in two individuals with PKS found their sSMCs consisted specifically of genetic material located in a stretch of chromosome 12 's p arm starting at its band 11 and running to its end.
[3] One suggested mechanism for the development of the sSMC in PKS involves three sequential events: 1) chromosome 12 suffers a nondisjunction, i.e. a failure of its homologous chromosomes or sister chromatids to separate properly during the second meiosis cell division that forms maternal eggs; 2) while most of the eggs with this nondisjunction die, a rare egg with the nondisjunction acquires a second structural aberration, isochromosome formation, that results in the creation of an extra chromosome consisting of copies of two or four p arms but no q arms of chromosome 12, i.e. the sSMC; and 3) the sSMC-containing egg, after being fertilized by a genetically normal sperm, develops into an offspring containing copies of this sSMC in some but not all cells, tissues, and/or organs consequently have some but not all of the defects associated with PKS.
[2] PKS is commonly diagnosed by detecting its causative sSMC as defined by identifying the overexpression of its genetic material.
(Small amounts of a fetus's DNA escapes through the placenta to circulate in the mothers blood.
This sSMC has been successfully detected (>90% of confirmed cases) in the DNA extracted by a buccal swab taken from the inside of an individual's cheek or the DNA extracted form an individual's cultured skin fibroblasts, i.e. fibroblasts from a skin biopsy grown in a laboratory for at least several days.
The sSMC in these tissues or cells is identified by multiplex ligation-dependent probe amplification (i.e. MLPA)[3] or microarray-based comparative genomic hybridization (i.e. array CGH).
[2] Because of mosaicism, testing an individual's circulating blood lymphocytes only rarely detects (i.e. gives mostly false negative rate) in true PKS cases.