A 10-year-old girl is brought to the office for evaluation of short stature. She was an average-sized infant, but over the past few years, her height growth velocity has plateaued. The patient has not menstruated and has no symptoms. She takes no medications, has no allergies, and has received all recommended immunizations. Menarche occurred in her mother at age 14 and both of her parents are tall. The patient's height is at the

Question

A 10-year-old girl is brought to the office for evaluation of short stature.  She was an average-sized infant, but over the past few years, her height growth velocity has plateaued.  The patient has not menstruated and has no symptoms.  She takes no medications, has no allergies, and has received all recommended immunizations.  Menarche occurred in her mother at age 14 and both of her parents are tall.  The patient's height is at the <5th percentile and weight is at the 50th percentile for age and sex.  She has no breast buds and no axillary or pubic hair.  She has a low hairline, a short and wide neck, a broad chest, and widely spaced nipples.  Which of the following is the most likely underlying mechanism for this patient's condition?

Quizplus · Accepted Answer

11ec160b_375b_1567_9249_63f4df6b0ba6_MD0001_00 Turner syndrome is a genetically heterogeneous condition that is most commonly due to meiotic nondisjunction during gametogenesis. The loss of one X chromosome in the sperm or egg results in a missing X chromosome in all of the patient's cells (45,X). In other patients, the nondisjunction event occurs during mitosis in early embryogenesis; these patients are missing the X chromosome in only some of their cells (mosaic Turner syndrome [45,X/46,XX]). A minority of patients have both X chromosomes, but one is structurally abnormal and missing some genetic material (eg, X fragments, isochromosomes). The loss of all or part of the X chromosome in Turner syndrome results in a missing SHOX gene, which normally promotes long bone growth. Therefore, patients with this syndrome typically have short stature. Meiotic nondisjunction is also responsible for Klinefelter syndrome and trisomies 13, 18, and 21. (Choice A) A balanced translocation is clinically silent as there is no excess or shortage of genetic material. However, a parent with a balanced translocation is at risk for having a child with an unbalanced translocation. An unbalanced trisomy 21 (in which one chromosome 14 contains the long arms of both chromosomes 14 and 21) is responsible for 3%-4% of Down syndrome cases. (Choice B) A frameshift mutation is a genetic mutation in which a number of nucleotides not divisible by 3 are inserted into or removed from a coding DNA sequence. As a result, the reading frame is shifted during protein translation, resulting in an entirely different peptide sequence (typically with formation of a premature stop codon). (Choice D) Trinucleotide repeat expansion is responsible for numerous diseases, including fragile X syndrome (CGG repeats), myotonic dystrophy (CTG repeats), and Huntington disease (CAG repeats). (Choice E) Uniparental disomy occurs when an individual inherits 2 copies of a chromosome from one parent and no copies of the chromosome from the other parent. For instance, although most often due to chromosomal deletions, uniparental disomy can also cause Angelman and Prader-Willi syndromes due to loss of expression of maternal/paternal imprinted components of a critical region of chromosome 15. Educational objective: Patients with Turner syndrome may have karyotype 45,X (complete monosomy), 45,X/46,XX (mosaicism), or 46,XX (with partial deletion of one X chromosome). Complete monosomy X usually results from meiotic nondisjunction during gametogenesis. __________ References: Prader-Willi syndrome and Angelman syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/20803659) Genetic considerations in the patient with Turner syndrome--45,X with or without mosaicism. (http://www.ncbi.nlm.nih.gov/pubmed/23020909)

A 10-Year-Old Girl Is Brought to the Office for Evaluation