A 2008 study, found a relationship between the PCDH19 gene and early onset<unk> seizures, with subsequent studies confirming the relationship. PCDH19 gene-related<unk>  can arise as a single case in a family, due to a de novo error in cell replication, or it can be inherited. In a large series of cases in which inheritance was determined, half of the PCDH19 mutations occurred de novo, and half were inherited from fathers in good health, and who had no evidence of seizures or cognitive disorders. Men and women can transmit the PCDH19 mutation, although<unk> , but not males, usually, but not always, exhibit symptoms, which can be very mild.<unk>  with a mutation have a 50% chance of having children who are carriers. Men have a 100% chance of transmitting the mutation to a daughter and 0% chance to a son. Although males do not generally exhibit PCDH19 gene-related history such as cluster seizures, in a study involving four families with PCDH19 gene mutations, 5 of the fathers had obsessive and controlling tendencies. The linkage of chromosome Xq22.1 to PCDH19 gene-related<unk>  in<unk>  was confirmed in all of the families. The inheritance pattern is very unusual, in that men that carry the PCDH19 gene mutation on their only X-chromosome are typically unaffected, except in rare instances of somatic mosaicism.11 Alternatively, approximately 90% of women, who have the mutation on one of their two X-chromosomes, exhibit symptoms. It has been suggested that the greater occurrence of PCDH19-epilepsy in<unk>  may relate to X-chromosome inactivation, through a hypothesized mechanism termed ‘‘cellular interference’’. A 2011 study found instances where patients had PCDH19 mutation, but their parents did not. They found that "gonadal mosaicism” of a PCDH19 mutation in a parent is an important molecular mechanism associated with the inheritance of a mutated PCDH19 gene. Genetics The PCDH19 gene is located on the long (q) arm of the X chromosome at position 22.1. The gene encodes for protocadherin 19, a transmembrane protein of calcium-dependent cell-cell adhesion molecules that is strongly expressed in neural tissue, such as the hippocampus, cerebral cortex, thalamus, and amygdala. Protocadherin 19 appears to be related to synaptic transmission and formation of synaptic connections during brain development. A mutation in the PCDH19 gene can cause the protocadherin 19 protein to be malformed, reduced in function or not produced at all. This abnormal expression of protocadherin 19 causes deficits in GABAergic signaling, causing the occurrence of seizures beginning in the early years of life. The expression of the PCDH19 mutation is highly variable, with some individuals appearing unaffected, and others showing severe disease. Even monozygotic twins with the mutation may have variations in seizure frequency and degree of cognitive impairment. Currently, the PCDH19 gene is the second most clinically relevant gene in the<unk>  field; the second largest number of<unk>  related mutations characterized thus far occur in the PCDH19 gene. The SCN1A gene, associated with Dravet Syndrome, is the most clinically relevant.
Epilepsy-intellectual disability in females
Schizophrenia and tobacco smoking
Supernumerary nipples–uropathies–Becker's nevus syndrome
Autism – Tics, AD/HD, and other Comorbidities
Mental retardation and microcephaly with pontine and cerebellar hypoplasia
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome
Craniosynostosis–anal anomalies–porokeratosis syndrome
Blepharophimosis, ptosis, epicanthus inversus syndrome