2. INDEX
History
Introduction
Classification of Turner Syndrome
Causes and risk factor
Epidemiology and Prevalence
Symptoms
Diagnosis
Management of Turner Syndrom
Growth Hormone Therapy
Diet
5/11/2019 2
Market share
4. Dr. Henry
Turner(1892-1972)
In 1938, an American doctor named Henry
Turner described a syndrome in women with
short stature and lack of development of
secondary sex characteristics. He also noted
that neck-webbing, or a skin fold on both sides
of the necks, was a common feature.
History
https://en.wikipedia.org/wiki/Turner_syndrome#cite_note-Mar2013-7
http://tsgalliance.org/about-ts/
5/11/2019 4
However, the correlation between Turner
syndrome and the X chromosome was not
made until 1959.
6. Introducti
on
Definition:
Turner Syndrome (TS) is a chromosomal condition that affects
development in females(only).
It involves a lack of part or all of a second sex chromosome(x) in some or
all cells. It affects 1 in every 2,500 baby girls.
5/11/2019 6
Other names:
45,X Syndrome
Ullirich –Turner Syndrome-Europe
Gonadal Dysgenesis- India
7. Introducti
on
Characteristics of Turner Syndrome :
Short stature
One of the missing gene on the X chromosome is the SHOX gene, which is
responsible for long
bone growth
The missing SHOX gene is the reason girls who have the disorder are
unusually short.
Other missing gene regulates ovarian development which influences sexual
characteristics
Non-functioning ovaries which causes infertility,
Webbed neck
Lymphedema of the hands and feet,
5/11/2019 7https://ghr.nlm.nih.gov/condition/turner-syndrome
9. Classification Of Turner
Syndrome
1. Classical Turner Syndrome
An X chromosome is completely missing. This affects about half of all
people with Turner Syndrome
Also known as Turner Mosaicism. It Is where the abnormalities occur only
in X chromosome in some of the body’s cells
2. Mosaic Turner Syndrome
3. Y chromosome material
A small number of people with Turner Syndrome have some cells with
just one X chromosome copy, and others with one X chromosome copy
and some Y chromosome material.
5/11/2019 9https://www.medicalnewstoday.com/articles/176083.php
11. Causes and Risk Factors
Causes:
Turner Syndrome is typically
caused by non disjunction.
Non disjunction occurs when a
pair of sex chromosomes fail to
separate during formation of
sperm (or egg)
Fig 1 :Non disjunction of sexual
chromosomes
5/11/2019 11https://www.biology.iupui.edu/biocourses/N100/2k2humancsomaldisorder
12. Risk Factors
Family history does not seem to be a risk factor
The loss or alteration of chromosomes occur randomly
There are no known toxins or environmental factors, ethnicity or location that
appear to increase the risk.
Having one child with Turner Syndrome does not increase the risk of having
other children with the condition.
https://www.medicalnewstoday.com/articles/176083.php5/11/2019 12
Causes and Risk Factors
14. Epidemiology and Prevalence
The prevalence of Turner Syndrome is based on the
prenatal and postnatal studies
Prenatal: The prenatal prevalence is much higher
than the postnatal . Prenatal diagnosis can be done by
testing the amniotic fluid
(legally termination of fetus possible in Denmark)
Postnatal: The postnatal prevalence of Turner
Syndrome is based on cytogenetic studies
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Fig 3: Prenatal prevalence of
Turner Syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290843/
https://academic.oup.com/jcem/article/91/10/3897/2656487
15. Karyotype
India
No. of
patients
(348)
Iceland
No. of
patients
(51)
China
No. of
patients
(62)
Mosaic pattern 33.33 % 42% 17.90%
Presence of Y
Chromosome
material
18.30 % 3% 8.10%
A Karyotype with
a chromosomal
structural
abnormality
(i(Xq) or i(Xp)),
2.59% 10% 43.50%
Classical Turner
Syndrome
19.3% 49%
Category Numbers
Worldwide
Conception abort
spontaneously
Affected girls having
45,X Karyotype
Girls lost paternal X
Mosaics girls(45,X/46
,XX/47 ,XXY)
Height
Every 1 girl among 2500
is suffering with Turner
Syndrome
99% (45,X)
50%
80%
50%
8 Inches or 20 cm
shorter than normal
adults
Tab 1:Data from different countries on Turner
Syndrome
Tab 2:Worldwide general statistics on Turner
Syndrome
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Epidemiology and Prevalence
17. Teen, Young and
old women
Less growth in childhood
Short height (20cm less
than expected),
Concepts learning
difficulty, Early end to the
menses, Sterile ,etc.
Before Birth
Excessive fluid collection
at
the back of the neck,
Heart Irregularities,
Abnormal Kidney
Infancy
Wide neck, Small lower jaw,
Narrow and high roof of
mouth
Low set ears, Broad chest and
widely spaced nipples, Arms
that turn outward at the
elbows,
Delayed overall bodyhttps://www.medicalnewstoday.com/articles/176083.php
Symptoms
5/11/2019 17
20. Diagnosis
Ultra sound
test
Chorionic Villus
Sampling(CVS)
FISH (fluorescent in
suite hybridization
) analysis
Chromosomal
Microarray
Analysis (CMA)
Amniocentesis
Detect chromosomal
abnormalities
Detect
chromosomal
abnormalities
A Karyotype
blood test
Detect extra or missing chromosomes,
rearrangements, breaks.
https://www.medicalnewstoday.com/articles/176083.php
5/11/2019 20
21. Diagnosis
Age of initiation of diagnosis of Turner Syndrome
- Statistics
5/11/2019 21
https://adc.bmj.com/content/90/3/267
23. Management of Turner Syndrome
There is no permanent cure for the Turner Syndrome but many of the associated
symptoms can be treated.
If a girl is diagnosed with the Turner Syndrome the following areas may be
monitored throughout her life:
Middle ear infection
High blood pressure (Hypertension)
Thyroid gland (Hypothyroidism)
Glucose levels (Diabetes)
Bone Mineral Density (Osteoporosis)
(bone mineral density can be measured by using dual energy x-ray absorptiometry (DEXA)
scan)5/11/2019 23
24. Management of Turner
Syndrome
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Growth Hormone
therapy
Estrogen therapy
The general recommendation is
to start a low dose of estrogen
replacement therapy at the age
of 12.
Individual sensitivity is variable.
Lifelong height is related to age,
time, and dose of treatment.
Oxymetholone
treatment
Other methods
Vitamin D
supplementation; active
lifestyle.
Marked effect when used in
combination with growth hormone.
Fertility, reproductive
assisted technologies
and pregnancy
Psychological
therapy
https://www.nichd.nih.gov/health/topics/turner/conditioninfo/treatme
26. The goal of Growth-promoting therapies are
to facilitate attainment of height during
childhood and adulthood, that minimizes
physical restrictions and allows puberty to
begin at an age similar to peers.
The centerpiece of growth-promoting therapy
is GH, which increases Height Velocity and
results in modest increases in adult stature for
most patients.
Growth Hormone Therapy
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Fig 5: Growth Hormone Therapy
27. Growth Hormone Therapy
Efficacy of growth hormone
The efficacy of growth hormone can be explained by using following
statistical data
Growth Hormone 3 weeks 6 weeks
The mean increment in height during 2 years 8.6cm 11.3cm
Increment in height standard deviation score 0.6cm 0.9cm
Growth velocity
1st year
2nd year
5.2cm/year
3.4cm/year
6.6cm/year
4.7cm/year
Increment in height standard deviation score for bone age 0.4cm 0.8cm
Patients with initial bone age was more than 13 years
1st year
2nd year
1-2cm
No
increment
1-2cm
No
increment
https://www.ncbi.nlm.nih.gov/pubmed/14969495/11/2019 27
Tab 3: Statistical data of efficacy of Growth Hormone
28. Growth Hormone Therapy
Factors influencing the efficacy of the Growth Hormone
Mid-Parental Height (MPH),
Duration of therapy and GH dose
Age at the initiation of GH treatment,
GH dosing strategies and addition of supplemental oxandrolone or low-dose
estrogen
Difference between baseline height SD score and MPH SD score; maternal
height SD
score; Weight SD score.
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29. Growth Hormone
Therapy
Ideal age for Growth hormone treatment
The optimal age for initiation of GH treatment has not been firmly
established, but various research data reveals that ideal age for the
treatment of growth hormone is at least 4 years prior to puberty
Relatively early GH initiation, around 4–6 years of age, is likely to result in
greater height gains during childhood and allow for age-appropriate induction
of feminization, such that the goals for both optimal adult stature and timing of
puberty can be achieved.
Therapy may be continued until the girl is satisfied with her height or until
little growth potential remains (bone age ≥13 years and HV)
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30. Growth Hormone Therapy
Generally the dosage of administration of growth hormone varies from country to
country
Location Dosage
North America 0.35-0.37 mg/kg/week
Europe 1.3-1.4mg/kg/week
Australasia 4.5-9.5mg/kg/week
Administered in divided doses 7 days/week
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31. Growth Hormone Therapy
Safety of GH treatment
Safety of GH treatment in Turner Syndrome in long-term clinical trials has
generally been reassuring with respect to
Blood pressure,
Cardiovascular diseases
Carbohydrate and lipid metabolism, Body composition, Bone
mineralization,
Body proportions and prevalence and
Hearing loss.
However, it is important to recognize that clinical trials are not powered for
these safety endpoints and absence of evidence of a safety signal is not
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32. Growth Hormone Therapy
Side Effects of GH
Risk of Intracranial Hypertension,
Slipped capital Femoral Epiphysis,
Scoliosis,
Rare case reports of Neoplasia in GH-treated patients with Turner Syndrome.
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33. Growth Hormone Therapy- Clinical Evidence
Effect of Growth Hormone on early brain development of girls with Turner
Syndrome:
University North Carolina in collaboration with Pfizer performed the interventional
study of Somatropin on 17 participants age of 11-13 months.
Administration of GH has started at the age of 12 months until 24 months .
Drug: Somatotropin 5mg pens with cartridge
Dosage regime: 50mcg/kg/day to be adjusted at 4 months intervals to closest
0.1mg
Route of administration: Subcutaneous Injection
Outcomes: Percentage change in total brain volume was determined by
magnetic resonance imaging within 12 months of therapy.
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34. Growth Hormone Therapy- Clinical evidence
5/11/2019 34
Volume of Brain lobes % Increase with
GH
Occipital 14.83
White Matter Tracts 15.12
Central 17.63
Frontal 15.43
Temporal 10.79
Parietal 18.86
Total Brain Volume 18.22
https://clinicaltrials.gov/ct2/show/NCT01367834?cond=%22turner+syndrome
%22&rank=6
Results
35. Growth Hormone Therapy-Clinical evidence
Effect of Growth Hormone on very young girls with Turner Syndrome:
Merck performed the interventional study of r-hGH (Saizen) on 115
participants of age 9 months - 4 years
Study centre: Germany
Drug: r-hGH (Saizen )
Dosage Regime: 0.35mg/kg/day for first two years, 0.5 mg/kg/day for next
two years
Route of Administration: Subcutaneous Injection
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36. Growth Hormone Therapy-Clinical evidence
Measured Outcomes:
Height at the end of 2 years were assessed,
Middle year infection assessed with 4 month interval,
Hearing problem assessed annually,
Cognitive and behavioral development assessed annually.
Results
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Growth
Velocity
Mean Increase
H-SDS −2.33±0.73 to −1.35±0.86
SDS
(about 1.0 SDS)
HV-SDS -1.22±1.57 to −0.44±1.35
(about 0.8 SDS)
https://eje.bioscientifica.com/view/journals/eje/164/6/891.xml
37. Growth Hormone Therapy- Effect on other Body
Parts
5/11/2019 37https://accesspediatrics.mhmedical.com/content.aspx?bookid=1082§ionid=6146
1925
Bone Metabolism
Increase in osteoclast differentiation and
osteoblast activity
Increase in bone mass by endochondrial
bone formation
Linear Growth
Promotes epiphyseal growth
Stimulates the diffentitation of
prechondriocytes and local expression of
IGF 1 which increases clonal expansion
of osteoblast (Dual Effector theory)
Adipose Tissue
Increases lipholysis, Inhibits lipoprotein
lipase
Stimulates hormone sensitive lipase
Decreases glucose transport, lipogenisis
Muscles
Increases amino acid transport , nitrogen
retention, metabolically active tissue and
energy expenditure, may effect muscle fiber
distribution
38. Growth Hormone Therapy
Conditions where Growth Hormone is not used:
To increase height in children after the growth plates have closed.
In patients with diabetes who have certain types of diabetic retinopathy(eye
problems).
In patients who have been recently diagnosed with cancer or who are being
treated for cancer.
In patients who are critically ill because of surgery, trauma, or respiratory
failure.
If it is shown that a previous brain tumor has come back or is getting larger.
A small number of patients treated with growth hormone have had increased
pressure in the brain. This can cause headaches and problems with vision.5/11/2019 38
39. Growth Hormone Therapy
Conditions where Growth Hormone is not used: (contd…)
Thyroid function should be checked regularly during Growth Hormone
therapy. Thyroid hormone replacement therapy should be started or
adjusted if needed.
Patients treated with Growth Hormone should be checked regularly for
low serum cortisol levels and/or the need to increase the dose of the
glucocorticoids they are taking.
In children experiencing rapid growth, curvature of the spine may
develop or worsen. This is also called scoliosis.
Growth Hormone deficiency can be caused by brain tumors. So, the
presence of these brain tumors should be ruled out before starting the
5/11/2019 39
40. Growth Hormone Therapy
Conditions where Growth Hormone is not used: (contd…)
In children experiencing rapid growth, limping or hip or knee pain
may occur. The child’s doctor should be notified and the child should
be examined.
Growth Hormone should only be used during pregnancy if clearly
needed. It should be used with caution in nursing mothers because it
is not known whether Growth Hormone is passed into human milk.
Use a different place on the body each day for Growth Hormone
injections. This can help to prevent skin problems such as lumpiness
or soreness.
Some cases of pancreatitis have been reported rarely in children
5/11/2019 40
42. Growth Hormone Therapy-Genotropin
Genotropin is a recombinant human growth hormone with an amino acid
sequence that is identical to the growth hormone of the human pituitary gland. It
has been used to treat more than 83,000 children around the world. It has been
in use for more than 30 years.
Genotropin is approved by the Food and Drug Administration (FDA) for the
treatment of several growth disorders in children and adults, including:
Growth Hormone Deficiency (GHD) in children & adults
Small for Gestational Age (SGA) in children
Idiopathic Short Stature (ISS)† in children
Prader-Willi Syndrome (PWS)‡ in children
Turner Syndrome in girls5/11/2019 42
43. Growth Hormone Therapy-Genotropin
Dosage forms and strengths of Genotropin:
Genotropin lyophilized powder:
5 mg two-chamber cartridge (green tip, with
preservative): concentration of 5 mg/mL
12 mg two-chamber cartridge (purple tip, with
preservative): concentration of 12 mg/mL
Genotropin Miniquick
A two-chamber cartridge of Genotropin (without
preservative) 0.2 mg, 0.4 mg, 0.6 mg, 0.8 mg, 1.0
mg, 1.2 mg, 1.4 mg, 1.6 mg, 1.8 mg, and 2.0 mg
5/11/2019 43
Fig 6: Genotropin cartridges
44. Growth Hormone Therapy-Genotropin
Tab 4:Outcomes of Genotropin compared to other drugs in turner syndrome
Outcome Romer et.al. Shish et.al
Genotropin Omnitropine Genotropin Humatrope Saize
Height, cm N=45 N=44 N=5 N=5 N=5
Mean change from baseline, 8.4 8.6 11.3 9.4 11.1
Difference in change between
groups(95%) CI.
0.23(-0.59-1.06) NR
HV, cm per year
6.8 6.9
-0.20(-1.34-0.96)
7.9 5.4
7.4
NR
Mean change from baseline,
Difference in change between
groups(95%) CI.
HtSDS
Mean change from baseline, 0.67 0.73 1.33 0.66 1.06
5/11/2019 44
45. HVSDS
Mean change from baseline, 7.28 8.14 NA
Difference in change between
groups(95%) CI.
0.76(-0.57to 2.10)
WDAEs, N% 0 0
Subject with SEs, N% NR 0
IGF 1
Mean change from baseline,
Difference in change between
groups(95%) CI.
172.6ng/ml 154.3
ng/ml
18.13
1.22 ng/ml 1.976ng/ml
2.44ng/ml
Genotropin -0.45 versus
Humatropine -0.73 versus Saize
Difference in change between
groups(95%) CI.
0.12(-0.06-0.30) NA
Growth Hormone Therapy-Genotropin
https://www.cadth.ca/sites/default/files/cdr/clinical/SR0333_GenotropinGHD-P_CL_Report_e.pdf
5/11/2019 45
46. Growth Hormone Therapy-Genotropin
Side effects:
In studies of Genotropin in children with Turner Syndrome, other side effects
included;
Flu, throat, ear, or sinus infection,
Runny nose,
Joint pain, and
Urinary tract infection.
5/11/2019 46
49. Diet
Ovarian failure is risk factor
for osteoporosis thus
adequate daily intake of
calcium (1.0-1.5 g) and
vitamin D (at least 400 IU)
should be considered
Patients with short stature
require fewer calories than
those of normal height.
5/11/2019 49
Fig 7: Diet for Patients with
Turner syndrome
51. Global Market Share of Turner
Syndrome
5/11/2019 51
Dominates the global Turner
Syndrome market owing to
increasing adoption of new
technologies and huge patient
population.
America
Is the second largest
market, in the global
Turner Syndrome
market. Rising research
and development in
healthcare sector, huge
patient population,
growing biotechnology
sector are the major
drivers for the market
growth within the region.
Europe
Region is the fastest
growing market.
Increasing awareness
for women health, rising
healthcare expenditures
and growing healthcare
sector are the major
drivers for the market
growth within the region
during the forecast
period.
Asia pacific
36% 30% 23%
Has the least share in the
global Turner Syndrome
market. The presence of poor
economies and stringent
government policies,
especially in the African region
restrains the market growth
within the region
Middle east
&Africa
11%