A 22-year-old woman, who recently relocated, comes to the office for a new patient visit. She has mild intellectual disability and has completed a high school level of education. The patient has no major health problems but reports persistent swelling of the hands and feet. Menarche occurred at age 13, and she has regular menstrual cycles. Physical examination shows short stature and a webbed neck. Karyotype analysis performed on peripheral leukocytes shows that 40% of the cells have a 45,X genotype and that the remaining 60% contain a 46,XX genotype. Which of the following is the most likely cause of this patient's condition?

Question

A 22-year-old woman, who recently relocated, comes to the office for a new patient visit.  She has mild intellectual disability and has completed a high school level of education.  The patient has no major health problems but reports persistent swelling of the hands and feet.  Menarche occurred at age 13, and she has regular menstrual cycles.  Physical examination shows short stature and a webbed neck.  Karyotype analysis performed on peripheral leukocytes shows that 40% of the cells have a 45,X genotype and that the remaining 60% contain a 46,XX genotype.  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec160b_3759_8ec4_9249_e9f725246b08_MD0001_00 This patient with mild intellectual disability, lymphedema, short stature, webbed neck, and 2 karyotypes evident on analysis likely has mosaic Turner syndrome. Mosaicism is defined as the presence of multiple, genetically different cell lines within the body. It can result from several processes, including chromosomal nondisjunction and mutations during the first stages of embryonic development. The earlier the error happens, the more daughter cells are affected. Mosaicism can be classified as germline, somatic, or both: Somatic mosaicism affects the cells forming the body, causing disease manifestations to develop in affected individuals. 45,X/46,XX is the most commonly diagnosed mosaicism affecting sex chromosomes. These patients typically have a milder form of Turner syndrome or can be asymptomatic, depending on the ratio of abnormal to normal cells. Germline mosaicism affects the cells that give rise to gametes, allowing the affected genes to pass to the offspring. The chance of a child being affected depends on the proportion of gametes that carry the mutation. When mosaicism is limited to the germline, the affected parent does not develop clinical manifestations. (Choice A) Chromosomal deletions can be either macro or micro, depending on how many base pairs are eliminated. Neither process results in the elimination of entire chromosomes or the presence of multiple cell lines within the body. (Choice B) Complete monosomy X also causes Turner syndrome. However, it would not explain the 2 separate genotypes seen on karyotyping. (Choice C) This patient has manifestations of Turner syndrome and peripheral cells with multiple distinct genotypes, which indicates that she has somatic mosaicism. If the mitotic error occurred very early in embryogenesis, before separation of the germline, she could also have germline mosaicism. However, germline mosaicism would not be the cause of her clinical manifestations and would not be detectable on karyotyping of a blood sample. (Choice E) Uniparental disomy describes the phenomenon wherein both chromosomes in a given pair come from one parent. In such cases, patients still have the full complement of chromosomes on karyotyping. (Choice F) In women, one X chromosome is normally inactivated in each somatic cell to maintain proper gene dosage. Despite the presence of only one functional X chromosome in each cell, both are still detectable on karyotyping. Educational objective: Mosaicism is defined as the presence of multiple, genetically different cell lines within the body. It can result from several processes, including chromosomal nondisjunction or a mutation during the first stages of embryonic development. Somatic mosaicism results in a mixture of normal and mutated somatic cells, often leading to a milder form of the disease. __________ References: Turner syndrome: diagnosis and management. (http://www.ncbi.nlm.nih.gov/pubmed/17708142) Genetic considerations in the patient with Turner syndrome--45,X with or without mosaicism. (http://www.ncbi.nlm.nih.gov/pubmed/23020909)

A 22-Year-Old Woman, Who Recently Relocated, Comes to the Office