Sex chromosome disorders Notes

Chapter 2 Acyanotic Defects NOTES SEX CHROMOSOME DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Disorders caused by numeric abnormalities (addition/loss)/structural damage of one/ both sex chromosomes (X, Y) ▪ Occur in approx. 1/448 live births ▪ Phenotypes less severe than autosomal defects due to X chromosome inactivation, low gene content of Y chromosome SIGNS & SYMPTOMS ▪ Delay in puberty onset, absence of menstruation, ambiguous genitalia, infertility DIAGNOSIS LAB RESULTS ▪ Prenatal fetus chromosomal analysis ▫ Amniocentesis, chorionic villi sampling of placenta TREATMENT MEDICATIONS ▪ Hormone replacement therapy OTHER INTERVENTIONS ▪ No corrective treatment available KLINEFELTER'S SYNDROME osms.it/klinefelters-syndrome PATHOLOGY & CAUSES ▪ Extra copy of X chromosome in individuals who are biologically male due to sex chromosome nondisjunction during maternal/paternal meiotic division ▪ Most common ▫ 47, XXY karyotype ▪ Less common ▫ Greater/lesser numbers of X chromosome 48,XXXY, 49,XXXXY, 46,XY/4,XXY mosaicism karyotypes ▪ Greater number X chromosomes → greater phenotypic abnormalities ▪ Most common sex chromosome abnormality; occurs in approx. 1/1000 live births ▪ Leads to primary hypogonadism, impaired cognitive development COMPLICATIONS ▪ Increased risk for psychiatric disorders, autism ▪ Problems with social interactions ▪ Delayed speech, language competence Predisposition to diseases ▪ May result in death ▪ Pulmonary ▫ Chronic bronchitis, emphysema ▪ Thromboembolic cancers ▫ Germ cell tumors, breast cancer OSMOSIS.ORG 173

(morbidity much higher in individuals with Klinefelter), non-Hodgkin lymphoma ▪ Leg ulcers ▪ Diabetes mellitus SIGNS & SYMPTOMS ▪ Newborns who are biologically male, phenotypically normal (e.g. with male external genitalia) ▪ Tall stature with decreased upper to lower extremity ratio due to decreased levels of testosterone, unsuppressed folliclestimulating hormone (FSH), luteinizing hormone (LH) ▪ Decreased testes size ▪ Increased levels of serum FSH, LH ▪ Variably decreased levels of serum testosterone → breast enlargement (increased risk of breast cancer); reduced facial, body hair; infertility DIAGNOSIS LAB RESULTS ▪ Blood/urine test ▫ Abnormal hormone levels ▪ Karyotype analysis OTHER DIAGNOSTICS ▪ Postnatally, observe signs of physical clinical manifestations ▫ Evaluation for infertility, enlarged breast tissue ▫ May present with cryptorchidism (undescended testes) TREATMENT MEDICATIONS ▪ Testosterone replacement therapy; stimulate changes that typically occur during puberty (e.g. facial, body hair growth; increased muscle mass, penis size; improved bone density) SURGERY ▪ Breast tissue removal PSYCHOTHERAPY ▪ Psychological counseling OTHER INTERVENTIONS ▪ Sex chromosome changes can’t be corrected ▪ Supportive therapy minimizes adverse effects, improves quality of life ▫ Speech therapy ▫ Fertility treatment Figure 27.1 The body habitus of an individual with Klinefelter’s syndrome. The body type is rounded with prominent gynecomastia. 174 OSMOSIS.ORG

Chapter 27 Sex Chromosome Disorders TURNER SYNDROME osms.it/turner-syndrome PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Completely/partially missing X chromosome in individuals who are biologically female ▫ Monosomy 45,X karyotype (most common) ▫ Mosaic X chromosome monosomy: 45,X/46,XX, 45,X/46,XY ▫ X chromosome abnormalities ▪ Newborns ▫ Congenital lymphedema (hands, feet), webbed neck, short fourth metacarpal ▪ Short stature, broad chest with widely spaced nipples, low hairline COMPLICATIONS DIAGNOSTIC IMAGING ▪ Primary hypogonadism ▪ Predisposition to several diseases, may result in death ▫ Cardiovascular: typically involves left outflow, coarctation of aorta (e.g. aortic valve abnormalities, elongated transverse aortic) ▫ Congenital renal anomalies: system, positional malformations ▪ Hearing loss, hypothyroidism, liver function abnormality incidences increase with age ▪ Low bone mineral density (BMD) ▫ Prone to fractures ▪ Ovarian insufficiency, infertility: premature oocyte death, degeneration of ovarian tissue ▪ Increased risk for learning disabilities, attention-deficit/hyperactivity disorder (ADHD) DIAGNOSIS Fetal ultrasound ▪ Cardiac/renal abnormalities, short femur LAB RESULTS ▪ Karyotype analysis TREATMENT MEDICATIONS ▪ Growth hormone therapy ▫ Promote height and bone growth ▪ Estrogen therapy ▫ Promote breast, uterine development OSMOSIS.ORG 175