Turner Syndrome Presentation to TCGI Conference 2008

Turner Syndrome  Occurrence 1/2000 – 1/2500 (Rosenfeld 1994)  Characterised: primarily by short stature 95%- 100%  Prenatal or early postnatal premature ovarian failure (gonadal dygenesis)  Physical features  Associated problems  Studies by Stanhope & Fry 1995: intelligence distribution same as general population

Diagnosis  Prenatal u/s – fluid neck lymphatic system  Birth: characteristic features oedema hands/feet, cardic cond chromosomes  Childhood: short stature cardiac conditions, speech/hearing  Adolescence: no pubertal spurt, no sexual development  Adulthood: failure to menstruate, infertility, premature menopause (have some ovarian function to enter spontaneous puberty)

Chromosome Analysis  Turner syndrome occurs when one of the two X chromosomes is missing, giving 45X instead of 46XX  50% have 45X in all cells  20% have mosaic pattern: some cells will have 46XX, other cells 45X  30% have 46XX where various rearrangements of the 2 nd X, ie ring shape, short p long q arm of X

Growth  Childhood Growth: Grow at normal rate for 2-3 years After 3-4 years growth rate decreases  Adolescent Growth No pubertal spurt: ovarian failure – no oestrogen TS girls continue to grow late teens Mean final height cm (Ranke 1994)

Ovarian Failure  weeks in utero ovaries develop normally  Decrease in oxytes elements of connective tissue (streaks) begin to occupy ovaries  Wide variation 10%-20% spontaneous pubertal development 2%-5% spontaneous menses Most not fertile occasional pregnancies have occurred – mosaic type

Key Issue Growth Hormone  Allows girl grow similar to peers  Major positive factor  Ranke suggests from his studies 7 year old untreated average 107cm which is 13cm shorter than normal mean. On GH, height should improve by 9cm. 13 year old untreated average 25cm shorter. On GH, should give height within 4cm of normal range.

Growth Hormone  Children with TS have a growth deficiency but not a hormone deficiency and therefore have some lack of sensitivity to the hormone.  Growth Hormone Stim Tests normal  Doses higher than those used in GHD  GH is manufactured by recombinant DNA technology to produce a sequence identical to human GH

Growth  GH is given for a few years  Many studies to determine optimal age to commence and discontinue GH  Influence of MPH  GH d/c epiphyes closed – growth complete  Bone Age  GH does improve final height (7cm)

Management  Common Tests / Clinic Visits  IGF1 / IGFBP3 monitor growth  Auxology  Blood pressure  TFTs  LHFSH  Renal  Bone age  Audiology

Optimal Management  Coarctation of aorta usually presents in infancy – surgery  Aortic stenosis less common - surgery  Bicuspid aortic valve 13%-34% - Echo - Surveillance & endocarditis prophylaxis  Cardiac Referral Echocardiography at diagnosis  Re-evaluate 10 years  Reassessment – adult transfer

Optimal Management  MRI magnetic resonance angiography be used in addition to echocardiography to evaluate cvs  Advice re pregnancy and exercise where cardiac condition present  Yearly blood pressure

Puberty  GH & Oxandrolone at 9 yrs  Pubertal induction  Puberty should not be delayed to promote increased height  Oral Ethinyloestiodiol yrs if on GH easily enough 13 yrs optimal (Donaldon et al)  Importance of complying with long-term oestrogen replacement Feminization Bone health in adult years

Education Evaluation  Varies  Hearing check middle ear 50%-85%  Conductive deafness – ear infections – decrease with age  Audiological checks  Sensoneural loss 58% Stenberg 1998  Impaired visuospatial abilities  Some - difficulty maths

Long Term  Continued monitoring of hearing and thyroid function throughout life  Adults monitored for aortic enlargement, hypertension, diabetes and increased cholesterol & triglycerides

Quality of Life Study  Bannink et al (2005) Netherlands  Normal quality of life in those who reached normal height and had age appropriate pubertal devlopment