Turners Syndrome

Icha & Deswin

Scenario D
A, 17 years old girl, came to the doctor because she has never had a menstrual period. Her height is 132 cm. Normal proportional body weight. Her past medical history is significant for lifelong short stature. No history chronic disease like GIT or renal disease. Her psycho-motor development is average normal.

Additional Information: Dysmorphic is not clear, stage of puberty A1P2M2.

Term clarification
Mestrual period: Interval of blood discharge from womb Short stature: Height below average for 17 YO Psyco-motor: Pertaining to motor effect of cerebral / physic activity Dysmorphic: Abnormally in morfology development A1P2M2:
A1 Axilla with little fine hair P2 rambut Pubis halus, tumbuh sepanjang Labia M2 mammae dengan perluasan areola

Problem identification
1. A, 17 years old girl, came to the doctor because she has never had a menstrual period. 2. Her height is 132 cm and Her past medical history is significant for lifelong short stature. 3. Stage of puberty A1P2M2.

Problem Analysis
1. The first problem What is menstrual period ? What is mechanism of menstrual period ?and how long ? What cause of late menstrual period ? and how the mechanism ? What is the effect of late menstrual period ? When the normal first menstrual period (menarche)? What is correlation between menstrual period and puberty ? 2. The second problem what is the normal rate of height for 17 YO girl ? What is the factor that inhibit the body growth ? How the endocrine system control body growth ?

3. The third problem

What is the interpretation of A1P2M2 ? What is the factor that influence puberty status? What is the normal stage of puberty status for 17 yo girl?
How to diagnose ? What is the diagnose? What is the treatment ? What is the prognosis ? what is the prevention ? what is the complication ?

Hypothesis
A, 17 years old girl, suspected of Turners syndrome because she have amenorrhea, delayed puberty and short stature.

Synthesis

Menarche
Menarche is the first menstrual period or the first menstrual bleeding in the females of human beings. Age of menarche :
usually occurs about 2 years after the breast develop ( telarche ) between 4 and 6 months after the growth of pubic and underarm hair most commonly happen between age 12 years old and 13 years old normally happen as early as age 9 years old or up to age 15 years old

Normal menstrual cycle

1. 2. 3. 4. Cycle length : 21-35days Cycle duration : 2-7 days Volume of menstrual bleeding up to 80 ml Cycle are regular and predictable from month to month

The Menstrual Cycle

The corpus luteum begins to degrade after ~8 days. Progesterone support falls off, and the endometrium arteries constrict Menstruation begins; anterior pituitary inhibition drops and it begins to secrete LH and FSH again This cycle repeats every ~ 28 days

Amenorrhoea
1. is the absence of a menstrual period in a woman of reproductive age 2 type of amenorrhoea : Primary : the absence of menstruation in a woman by the age of 16 In Gonadal dysgenesis(turner syndrome),Mullerian agenesis, Androgen insensitivity syndrome, delay in hypothalamic-pituitary maturation, etc Secondary : menstruation has ceased - for three months in a woman with a history of regular cyclic bleeding In pregnancy, anovulation, menopause, premature menopause, etc

2.

Effect of late menarche : Disturbance of osteoblas activity Inhibit developing of secondary sex Osteoporosis Failure of reproduction function

Hormones which play a role in height & body development

1. Growth hormone -> GH stimulates our tissue body to grow, increase the size of cell , increase mitosis process that follow by the increasing of cell number, and differentiation of any cell type (especially bone and muscle) 2. Thyroid hormone -> for intrauterine growth / IUG 3. Insulin -> regulation of cell growth and development

Risk factors that can effect human growth

Genetic background Psychosocial Environmental Acute or chronic disease Nutrition Social economic aspect Some hormones: GH -> growth of osteocyte amount Thyroid hormone -> growth & maturity of bone Mans gonad hormone in testis & suprarenalis glands Womans gonad hormone in suprarenalis glands

Child Age

Average Height(cms)

Height Range(cms)

Average Weight(kgs)

Weight Range(kgs)

6 Months 1 2

74 74 86

70 - 80 67- 80 78 - 94

10 9 12

7.5 - 12 7.5 - 12 9 - 12

3
4 5 6 7 8 9 10 11 12 13 14 15 16

95
102 109 115 121 127 132 138 143 150 155 160 162 162

85 - 104
90 - 112 100 - 120 102 - 126 106 - 135 108 - 142 120 - 146 122 - 152 125 - 162 131 - 168 138 - 172 142 - 178 145 - 179 146 - 179

14
16 18 21 23 26 29 32 36 40 45 50 53 56

10 - 20
12 - 23 14 - 25 16 - 32 18 - 38 18 - 40 19 - 51 21 - 58 24 - 66 26 - 70 28 - 74 33 - 79 36 - 82 40 - 86

17

163

146 - 179

57

40 - 87

Short Stature
Is it normal for 17 years old with height 132cm? normal height for 17 yrs old = 148cm165cm So she was short stature.

Short stature
Short stature refers to any person who is significantly below the average height for a person of the same age and sex specifically, the shortest 3 - 5% of the population.

Cause of short stature:

Normal variation (generally familial or the causes unknown) 1. Familial or genetic short stature 2. Constitutional delay of growth and puberty or maturation Primer or intrinsic (disorder of cell or growth plate factor) 1. Syndrome that related with chromosome disorder 2. Another syndrome 3. IUGR that caused 4. Skeletal dysplasia or osteochondrodysplasia 5. Storage disorder

 Sekunder or external (disorder because external influence from growth fracture) 1. Chronic disease, example: malabsorbtion, generalized inflammatory disease, heart, lungs, liver, renal, hematology, CNS, intestine disorder, chronic anemia. 2. Malnutrition 3. Endocrine disorder 4. Metabolic disorder, such inborn errors of metabolism like Bartter Syndrome 5. Iatrogenic short stature, therapy steroid, radiation 6. Psychosocial short stature or emotional (Psychosocial dwarfism) Idiopathic Nothing disparity or disorder

Factor influence body height

Hereditary (genetic) Gender
In woman : Estrogen not only stimulates bone development but also mempercepat penutupan epifisis

Faktor lingkungan (ex: nutrisi)

Defisiensi Ca deficiency can influence the development and kepadatan of the bone

Exercise
Stimulates osteoblast activity

Hormon
Growth Hormone Thyroid Hormone Estrogen Hormone

 Is it normal for 17 years old with height 132cm? normal height for 17 yrs old = 148cm-165cm

Cause of life long short stature Constitutional Systemic Chronic disease Gene or abnormalities abnormality Intrauterine growth retardation Bone and cartilage abnormalities Psychology and social fact Endocrine disorder

Correlation short stature with menstrual (puberty): Ovary secretes the female sex hormones estrogen and progestrone Estrogen increases osteoblastic activity Estrogen causes early fusion of the epiphysis with the shaftv In this case, estrogen is not secreted, hence osteoblastic activity reduced Less growth (short stature)

Stadium Pubertas
A. Axilla Stage 1 : infantile. Rambut pada axial belum ada. Meskipun ada,hanya berupa rambut-rambut halus Stage 2 : rambut pada axilla tumbuh namun agak jarang Stage 3 : rambut pada axilla tumbuh secara merata dan teksturnya kasar B. Pubis Stage 1 : infantile. Rambut pada pubis belum ada. Meskipun ada, hanya berupa rambut-rambut halus Stage 2 : rambut rambut pada pubis tumbuh tetapi masih jarang Stage 3 : rambut pubis menjadi semakin gelap, lebih kasar, dan keriting. Distribusinya masih minimal Stage 4 : rambut pubis sudah tumbuh seperti rambut pubis dewasa Stage 5 : Rambut pubis tumbuh membentuk segitiga terbalik

 Mammae Stage 1 : infantile Stage 2 : berupa tonjolan kecil jaringan payudara. Mulai tumbuh pada usia 10,5 tahun Stage 3 : ukuran aerola mammae dan payudara sendiri bertambah semakin besar dengan kontur bulat. Muncul 12 bulan setelah stage 2 Stage 4 : puting susu dan aerola mammae bertambah besar dan bentuk tonjolan kedua di atas payudara. Muncul 12 bulan setelah stage 3 Stage 5 : tonjolan kedua yang tampak pada stadium 4 kini menjadi satu dengan kontur payudara. Perbedaan antara satge 4 dan stage 5 tidak begitu terlihat jelas Normalnya, pada perempuan usia 12 tahun, status pubertasnya sudah mencapai stage 3. Pada perempuan usia 16 tahun, status pubertasnya sudah mencapai stage 4 atau bahkan sudah mencapai stage 5.

Possible causes of delayed puberty

Variation of normal (constitutional delay) Prolonged high level of physical exertion / being an athlete Systemic disease, e.g. Inflammatory bowel disease, chronic renal failure Undernutrition e.g. anorexia nervosa, zinc deficiency Hypothalamic defects and diseases e.g. Prader-Willi syndrome, Kallmann syndrome Pituitary defects and diseases e.g. hypopituitarism Gonadal defects and diseases e.g. Turner syndrome, Klinefelter syndrome Absence or unresponsiveness of target organs e.g. androgen insensitivity syndrome, mullerian agenesis Other hormone deficiencies and imbalances e.g. hypothyroidism, Cushing's syndrome

diagnosis

How to diagnose?
Anamnesis : family history (puberty, syndromes), maternal history, labour history, Child history, primary illness history, nutrition, previous BH/BW, medication history, dentition history, Psychosocial history Physical examination : height, weight Secondary sexual characteristic mid parental height, sitting height, arm wide length, dysmorphism, stigma of syndromes Additional examination : Bone Age, chromosome (femalesind.Turner), chronic disease
Group b10

05.12.08

Laboratory Examination
Blood test, karyotype CT scan / MRI Hormonal Status; T4, TSH, gonadotropin, sex hormone, cortisol, GH

Therapy depend etiology

05.12.08

Group b10

DD
DD Kriteria Gangguan Turner Syndrome Noonan Syndrome GH deficiency Achondroplasi a Mutasi genetik autosomal dominan Hipotiroidisme nondysjunction + Sebagian besar tidak terjadi menarche Wanita terganggu Short stature

Autosomal dominan
-

GH inadekuat -

Tiroksin inadekuat

Herediter Proporsi

Siklus mens

normal

normal

normal

Normal

Jenis kelamin Puberty status Stature Psychomotor developm ent

Pria dan wanita normal Short stature

Pria dan wanita normal Short stature

Pria dan wanita normal Short stature

Pria dan wanita Normal Short stature

+/-

+/-

Diagnosis banding
Gejala-gejala
Webbed neck Short stature Retardasi mental Kelainan pubertas

Sindro turner
+ + +

dwarfism
+ -

Noonan sindrome
+ + + -

kretinisme
+ + +

kasus
+ +

Gangguan motorik
Akondroplas ia Gangguan menstruasi

+
+

+
-

Turner Syndrome
Turner syndrome (TS) is a chromosomal condition that describes girls and women with common features that are caused by complete or partial absence of the second sex chromosome. Karyotype 80 % 45, X0 20% mosaic form(46XX/45X0)

 Flat feet Small, narrow fingernails and toenails that turn up Short fourth metacarpals (the ends of these bones form the knuckles) Edema of hands and feet, especially at birth Intelligence TS individuals are on average of normal overall intelligence with the same variance as the general population. They do, however, often have difficulty with spatial-temporal processing (imagining objects in relation to each other), nonverbal memory and attention. This may cause problems with math, sense of direction, manual dexterity and social skills.

The Hormonal Regulation of Ovarian Activity

Pathofisiology of turners syndrome

Turner Syndrome

Classic
(45+XO)

Mosaic
(46+XX / 45+XO)

Gonadal dysgenesis

FSH & LH cant reaches the ovary

No germ cell to produce oosit

( - ) production of estrogen & progesteron

Primary amenorrhea

infertile

Short stature

Abnormal developmental of secondary sex

Pemeriksaan penunjang
1.Pemeriksaan karyotype Diagnosis dipastikan dengan adanya 45 X0. standar karyotyping yang digunakan adalah dengan menganalisis kromosom dari 30 limposit periferal 2.Pemeriksaan laboratorium
Penentuan kadar gonadotropin plasma merupakan cara yang paling praktis untuk membuktikan disgenesis gonad. Kadar FSH lebih tinggi dari pada LH dan selalu lebih tinggi daripada normal sebelum usia 6 th dan sesudah usia 10 th.

3.Pemeriksaan radiology
Tanda kosowicz dan tanda Archibald dapat membantu menegakkan diagnosis sindrom turner dan penentuan umur tulang, Bone age biasanya normal sebelum remaja tetapi tertuda setelahnya karea kekurangan hormon esterogen.

 Complication: Katarak Diabetes Scoliosis Arthritis Hashimotos Thyroiditis Hipertensi Gagal ginjal Infeksi telinga tengah obesitas

Prognosis
Overall prognosis is good. Even with growth hormone therapy, most individuals are shorter than average. Turner syndrome is not a cause of mental retardation. Life expectancy is slightly shorter than average but may be improved by attention to associated chronic illnesses, such as obesity and hypertension. Almost all individuals are infertile, but pregnancy with donor embryos is possible.