Cause
Mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body. Alterations in RB1 or MYCN can give rise to retinoblastoma. RB1
In children with the heritable genetic form of retinoblastoma, a mutation occurs in the RB1 gene on chromosome 13. RB1 was the first tumor suppressor gene cloned. Although RB1 interacts with over 100 cell proteins, its negative regulator effect on the cell cycle principally arises from binding and inactivation of the transcription factor E2F, thus repressing the transcription of genes which are required for the S phase.The defective RB1 gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. The expression of the RB1 allele is autosomal dominant with 90% penetrance.Inherited forms of retinoblastomas are more likely to be bilateral. In addition, inherited uni- or bilateral retinoblastomas may be associated with pineoblastoma and other malignant midline supratentorial primitive neuroectodermal tumors (PNETs) with a dismal outcome; retinoblastoma concurrent with a PNET is known as trilateral retinoblastoma. A 2014 meta-analysis showed that 5-year survival of trilateral retinoblastoma increased from 6% before 1995 to 57% by 2014, attributed to early detection and improved chemotherapy.The development of retinoblastoma can be explained by the two-hit model. According to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors.
Keratoderma climactericum is a skin condition characterized by hyperkeratosis of the palms and soles beginning at about the time of menopause. : 213

Causes
Keratoderma climactericum is either inherited through an abnormal gene, or it is acquired through a change in the health or environment of the individual. See also
Keratoderma
List of cutaneous conditions


== References ==