Turner Syndrome_ Practice Essentials, Background, Pathophysiology.pdf

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Turner Syndrome: Practice Essentials, Backg round, Pathophysiolog y

Practice Essentials Turner syndrome is one of the most common chromosomal abnormalities, occurring in approximately 1 in 2000 live-born female infants. [1, 2] Turner syndrome (see the image below) is caused by the absence of one set of genes from the short arm of one X chromosome.

Generalized lymphedem lymphedema a is seen here in an inf ant w ith Turner syndr s yndr ome. ome. The loose skin folds around the neck will f orm a webbed neck later in life.

Signs and symptoms At birth, girls with Turner Turner s yndrome m ay have have swollen hands and feet because of lymphedema. In infants, the combination of dysplastic or hypoplastic nails and lymphedema gives a characteristic sausage-like appearance to the fingers and oes. Infants also have a higher incidence of congenital hip dislocation. During childhood, girls with Turner syndrome usually present with short stature. [3] In older adolescents and adults, presenting symptoms usually involve issues of puberty and fertility as well as short stature.

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Turner Syndrome: Practice Essentials, Background, Pathophysiology

Short stature Growth rate in childhood is slightly slower; before age 11 years, some girls have height and growth rates that are well within the normal range, but heights are typically below the 50th percentile [3] The adolescent growth spurt is essentially absent Puberty Adrenarche, t he beginning of pubic hair growth, occurs at a normal age Breast development is absent when ovarian failure occurs before puberty Primary or secondary amenorrhea occurs with ovarian failure Other characteristic physical findings Dental: A high arched palate, sometimes with dental crowding or malocclusion Nails: Hypoplastic or hyperconvex nails Nevi: Excessive numbers of nevi, when compared to other family members WebbedMaala neck: S A Daniel, broad neck and a lowEdit or indistinct Author: MBBS ; Chief or: Luis Ohairline Rohena, MD more... Cubitus valgus (increased carrying angle) Madelung of the wrist Updated: Aug 07,deformities 2015 Short fourth and fifth metacarpals and metatarsals Shield chest: The chest appears to be broad with widely spaced nipples Lymphedema Eyes: Ptosis, strabismus, amblyopia, and cataracts; epicanthal folds can be present; red-green color blindness

Turner Syndrome

Ears: Serous otitis media is more common [4] ; the auricles may be posteriorly rotated or low set; hearing loss due to otosclerosis is common in adults GI bleeding: This is usually due to intestinal vascular malformations, but the incidence of Crohn disease and ulcerative colitis is also increased Scoliosis: This occurs in 10% of adolescents with Turner syndrome and may contribute to short stature Hypertension: May be caused by coarctation of the aorta or renal anomalies but often occur even in the absence of such findings Cardiac murmurs: Cardiovascular malformations include hypoplastic left heart [5] , coarctation of the aorta, bicuspid aortic valve, and aortic dissection in adulthood Thyroid: Hypothyroidism develops in 10-30% of patients [6] and is often associated with thyroid enlargement Cutis laxa: Loose folds of skin, particularly in the neck, are signs in

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newborns; this is a result of resolving lymphedema and occasionally is observed after infancy See Clinical Presentation for more detail.

Diagnosis Prenatal On fetal ultrasonography, Turner syndrome is suggested by the presence of a nuchal cystic hygroma, [7, 8] horseshoe kidney, left-sided cardiac anomalies, or nonimmune fetal hydrops Turner syndrome may be prenatally diagnosed by amniocentesis or chorionic villous sampling Noninvasive prenatal testing of maternal blood can be used to screen for Turner syndrome with great sensitivity and specificity. [9] Karyotyping A standard 30-cell karyotype analysis is required for diagnosis of Turner syndrome, to exclude mosaicism [10] Diagnosis is confirmed by the presence of a 45,X cell line or a cell line with deletion of the short arm of the X chromosome (Xp deletion) The buccal smear for Barr bodies is obsolete A male phenotype exc ludes the diagnosis, regardless of k aryotype [11] Patients with Turner syndrome should be investigated for the presence of Y chromosomal material using a Y-centromeric probe Laboratory studies Gonadotropins: Both LH and FSH may be elevated in untreated patients younger than 4 years; they are later suppressed to normal or near-normal levels, only to rise to menopausal levels after age 10 years [12] Thyroid function tests: Because of the high prevalence of hypothyroidism in Turner s yndrome, [6] obtain thyroid function tests at diagnosis; repeat TSH measurements every 1-2 years or if symptoms develop, because hypothyroidism may develop at a later age Glucose metabolism: Abnormalities of glucose metabolism, including overt diabetes mellitus, are more common than in unaffected children; screening for diabetes mellitus is best performed by obtaining a hemoglobin A1c or fasting glucose level; glucose tolerance tests should not be used for

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screening Renal studies At diagnosis, perform ultrasonography of t he k idneys and renal collecti ng system Annual urine cultures and m easurement of BUN and creatinine levels are recommended for those patients with abnormalities of the renal collecting system that predispose to obstruction Cardiovascular studies Perform echocardiography and/or MRI of the heart and aorta upon diagnosis Evaluate 4-limb blood pressures, because of the high incidence of coarctation of the aorta Audiology Infants diagnosed at birth should have a hearing assessment in the nursery Formal hearing assessment is recommended at age 1 year and before entering school Formal re-evaluation every 5 years has been recommended; more frequent testing is needed in children with repeated otitis media Adults should have a hearing evaluation at least once, with further test ing later if hearing loss is suspected See Workup for more detail.

Management Patients with Turner syndrome require screening for commonly associated chronic diseases. Early preventive care and treatment are also essential. [13] Growth hormone therapy In childhood, growth hormone therapy is standard to prevent short stature as an adult [14, 15, 16] The ideal age for initiating treatment has not been established; taller adult heights occur with the longest treatment durations before the start of puberty Growth hormone may have long-term favorable effects on lipids, even after it is discontinued. [17]

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Sex hormone replacement therapy Estrogen replacement therapy is usually required, but starting too early or using doses that are too high can compromise adult height Estrogen is usually started at age 12-15 years Continuous low-dose estrogens can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months; progestin can be added later Some authors believe that conjugated estrogens are contraindicated in pediatric patients [10] Transdermal estrogens are associated with physiologic estrogen levels [18] and may be the preferred treatment, if tolerated [10] Androgen replacement therapy is not the standard of care, [10] but may have favorable effects [19] Consultations Endocrinologist Cardiologist Nephrologist or urologist Psychologist Genetics Diet Both short stature and ovarian failure are risk factors for osteoporosis, and care should be taken to ensure adequate daily intake of calcium (1.0-1.5 g) and vitamin D (at least 400 IU) Patients should avoid obesity, which increases already high risks of hypertension and insulin resistance Patients with short stature require fewer calories than those of normal height See Treatment and Medication for more detail.

Contributor Information and Disclosures Author Maala S Daniel, MBBS Attending Physician, Division of Pediatric Endocrinology, Helen DeVos Children's Hospital Maala S Daniel, MBBS is a member of the following medical societies: American Academy of Pediatric s, American Medical Student Ass ociation/Foundation, Endocrine Society

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Disclosure: Nothing to disclose. Coauthor(s) Daniel C Postellon, MD Associate Professor or Pediatrics and Human Development, Michigan State University College of Human Medicine; Consulting Staff, Pediatric Endocrine Clinic, Helen DeVos Children's Hospital Daniel C Postellon, MD is a member of the following medical societies: American Academy of P ediatrics, Endocrine Society, Pediatric Endocrine Society, American Diabetes Assoc iation Disclosure: Nothing to disclose. Specialty Editor Board Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Nothing to disclose. Chief Editor Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Ass istant Professor of Pediatrics, University of Texas Health Science Center at San Antonio Luis O Rohena, MD is a member of the following medical societies: American Academy of P ediatrics, American Chemical Society , American College of Medical Genetics and Genomics , American Society of Human Genetics Disclosure: Nothing to disclose.

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Turner Syndrome_ Practice Essentials, Background, Pathophysiology.pdf

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