TURNERS SYNDROME

SONIKA SHIMON PRASAD

S160232
DEFINITION
Turners syndrome, a condition that affects only female, results
when one of the X chromosomes (sex chromosomes) is missing
or partially missing.
It can cause a variety of medical and developmental problems,
including short height, failure of the ovaries to develop and
heart defects.
HISTORY
Turner syndrome was first reported as a
clinical syndrome (prior to the availability
of karyotyping) in seven women with
short stature, sexual immaturity, neck
webbing, and cubitus valgus in a paper
published in 1938 by Henri Turner, an
Oklahoma physician
INCIDENCE AND PREVALENCE
• Turner syndrome is the most common sex chromosome
abnormality in females and occurs in approximately 1 in 2000
to 1 in 2500 live female births, based on epidemiological and
newborn genetic screening data from Europe, Japan, and the
United States.
• Turner syndrome occurs with more or less the same
prevalence in all ethnic groups and in different countries.
• There is decline in prevalence as there is increased use of
ultrasonography screening prenatally leading to pregnancy
termination.
PATHOGENESIS
• Normally, a girl inherits one X
chromosome from her mother and
one x chromosome from her
father. But girls who have Turners
Syndrome are missing one of their
X chromosome.
• It is caused by non-disjunction.
• Non-disjunction occurs when a pair
of sex chromosomes fails to
separate during formation of egg
or sperm.
 GENOTYPES ASCCOCIATED WITH TURNERS SYNDROME

• 45,X
• 45,X with mosaicism.
• X chromosome anomalies – Several types of anomalies in the X chromosome
can cause Turner syndrome, with or without mosaicism:
 Isochromosome Xq
 Ring chromosome X
 Xp or Xq deletion

• Turner syndrome with Y-chromosome mosaicism.

 GENES FOR CHARACTERISTIC TURNERS
SYNDROME PHENOTYPE
• The homeobox gene, SHOX (short stature homeobox-containing gene on the X
chromosome), is associated with short stature in Turner syndrome and in Leri-
Weill dyschondrosteosis. Short stature is the only clinical finding invariably
associated with the 45,X karyotype and SHOX deficiency; it also is the only
phenotypic abnormality present in virtually 100% of patients with Turner
syndrome.
• For gonadal insufficiency, a gene for bone morphogenetic protein 15 (BMP15) on
the short arm of the X chromosome (Xp), as well as two genes encoding fragile X
mental retardation protein or FMRP (FMR1 and FMR2), on the long arm (Xq) have
been implicated.
• For certain cardiac defects, loss of the X chromosome gene, TIMP1, and a
deleterious variation in TIMP3 that increases the risk of bicuspid aortic valve and
thoracic aortic aneurysms.
CLINICAL MANIFESTATIONS
TYPICAL FEATURES
• short stature
• "shield" chest with widely
spaced nipples
appearance
• a short and webbed neck
• cubitus valgus
• Madelung deformity of
the forearm and wrist
 SYSTEMIC MANIFESTATION
SYSTEM FEATURES
Short stature and skeletal anomalies • adult height in Turner syndrome is approximately 20 cm
below that of the general female population.
• Scoliosis,
• kyphosis
• short neck
• Madelung deformity
• cubitus valgus
• genu valgum

Reproductive • Primary hypogonadism

• premature ovarian failure
• no breast development
• primary amenorrhea

cardiovascular • Aortic valve disease and coarctation

• Aortic dissection
• Pregnancy and cardiovascular risk
• Hypertension
• Vaculopathy
• Conduction abnormalities.
Urinary system
Osteoporosis and bone health
Risk of malignancy
Ocular abnormalities
• collecting system malformations
• horseshoe kidneys
• Malrotated kidneys and other positional abnormalities
• obstruction of the ureteropelvic junction.
• Suboptimal estrogen replacement
• Underestimation of bone mineral density in short subjects
• Intrinsic bony abnormalities
• Gonadoblastoma
• Meningioma
• colon cancer
• Nearsightedness
• farsightedness
• strabismus
• Amblyopia
• epicanthal folds
• Ptosis
• hypertelorism
• red-green color blindness
• Keratoconus, glaucoma, anterior lenticonus, cataracts,
retinal vascular changes, and retinal detachment
Hearing and ear abnormalities
Autoimmune disorders
Metabolic syndrome and diabetes mellitus
Abnormal liver enzymes
Skin
• otitis media
• middle ear effusions
• conductive hearing problems
• eustachian tubes and cranial base
• Progressive sensorineural hearing loss
• Cholesteatoma
• hypothyroidism (Hashimoto's thyroiditis)
• celiac disease
• inflammatory bowel disease (IBD)
• Insulin resistance
• type 2 diabetes mellitus
• type 1 diabetes mellitus
• Increased alanine aminotransferase [ALT], aspartate
aminotransferase [AST], and gamma glutamyl
transpeptidase [GGT].
• steatosis or non-alcoholic fatty liver disease
• pilomatricoma
• pigmented nevi
• melanoma
• hypertrophic scarring and keloid formation
Psychologic and educational issues • severe mental retardation
• deficits in social cognition
• difficulty with nonverbal
• problem-solving tasks such as mathematics;
psychomotor deficits, such as clumsiness; and problems
with visual-spatial organization
• attention deficit disorder (ADD)
• neurodevelopmental abnormalities

Mortality • increased approximately threefold

DIAGNOSIS
• Prenatal- chorionic-villus sampling or amniocentesis, fetal
ultrasonography (septated cystic hygroma, lymphangiectasia
(fetal hydrops), cardiac defects, nuchal thickening, kidney
anomalies, or short femur). Positive results from noninvasive
prenatal testing (NIPT) such as with cell-free DNA in maternal
blood.
• Newborn period- apparent at birth, presenting with congenital
lymphedema of the hands and feet, webbed neck, nail dysplasia,
narrow and high-arched palate, and short fourth metacarpal.
• Infants and children- unexplained growth failure, defined as a
growth velocity less than the 10th percentile for age or stature
that is substantially less than predicted from parental heights.
• Adolescence- failure to start or complete breast development,
or those with secondary amenorrhea, especially if short
stature and/or other features suspicious of Turner syndrome,
 DIAGNOSTIC TESTS
• Standard karyotype analysis
• Prenatal diagnosis
 Karyotype analysis
 Real-time PCR
 High-throughput pyrosequencing
 Whole-exome sequencing

• Other tests- Renal ultrasonography, Comprehensive cardiovascular evaluation.

• Laboratory tests
 Age 4 years and older – Serum thyrotropin (thyroid-stimulating hormone [TSH]), to screen
for chronic autoimmune thyroiditis, and tissue transglutaminase (tTG) with total
immunoglobulin A (IgA), to screen for celiac disease.
 Age 10 years and older – Fasting blood glucose, glycated hemoglobin (A1C), alanine
aminotransferase (ALT) and aspartate aminotransferase (AST), serum creatinine, and
urinalysis, because of the risks of diabetes mellitus, fatty liver disease, and kidney
dysfunction.
 MANAGEMENT
CONDITION INVESTIGATION TREATMENT

Short stature Growth curve specific for TS. Growth hormone therapy
Indications: height falls below 5th percentile for age on normal
female growth chart (2-5years)
Dosing: 0.35 – 0.375mg/kg/week max 67mcg/kg/day
Side effects: intracranial HTN, SCFE, pancreatitis.
Severe short stature Growth hormone therapy + adjunctive oxandrolone
Dosing: 0,03mg/kf/day max 0.05mg/kg/day OR
Growth hormone + delayed pubertal induction
Primary Serum anti-mullerian hormone Estrogen therapy
hypogonadism Serum Follicle stimulating Dosing: 3.125-6.25mcg/day (transdermal estradiol patch)
hormone/ LH Micronized 17-beta estradiol 0.25mg/daily (orally)
Inhibin B Depot estradiol 0.2-0.4mg IM monthly
Adjunctive progestins
Dosing: micronized progesterone 200mg/day for 12 days
Cardiovascular BP measurement UL and LL
ECG- conduction abnormalities eg
prolonged QT interval
Cardiac imaging- coarctation of aorta,
bicuspid aortic valve etc.
Cognitive function and learning Developmental and behavioral
disabilities screening until adulthood
Neurophysiological assessment
Hearing Tympanometry and audiology
Scoliosis and kyphosis Visual inspection
Radiographic inspection
Renal anomalies and UTI Renal ultrasound
Ophthalmology Ophthalmologic examination
Edema Clinical assessment UL and LL
Coarctation of aorta- surgery
Prolonged QT interval- no antiarrythmic, non
sedating antihistamines, antimicrobials etc.
Bicuspid aortic valve- no antmocrobial
prophylactic is required.
Aortic dilation- BP management ( beta
blockers exercise restriction, ACE inhibitors)
and surgery.
Appropriate academic and occupational
adjustments.
Ent specialist
Orthopedic specialist
Nephrologist
Eye clinic
Support stocking, lymphatic drainage,
massage therapy, physical therap
celiac disease Measure tissue transglutaminase gluten free diet
immunoglobulin A antibodies

Autoimmune thyroiditis Measure thyroid stimulating hormone Treat accordingly if hypo or hyper.
and free thyroxine (T4)

Liver disease Measure alanine aminotransferase, Estrogen replacement therapy.

aspartate aminotransferase, gamma
glutamyl transpeptidase and alkaline
phosphatase.
Metabolic syndrome Measure HBA1C w/wo fasting glucose. Treat diabetes and cholesterol levels.
dyslipidemia

Vitamin D deficiency Measure serum 25-hydroxyvitamin D Dietary intake of vit D and calcium
supplements.

Gonadoblastoma Screen for Y chromosome mosaicism Prophylactic removal of gonads

on karyotype (opphorectomy or salpingo-
oophorectomy)
REFERANCES
• UP TO DATE
• MEDSCAPE
• OP GHAI