reproductive gynae spiels Flashcards
Swyers syndrome
Swyers syndrome described 46 XY gonadal dysgenesis
MDT
Referral to SW and psychology
Written information
The non functioning gonads have a high malignant potential 20-30 % and should be surgically removed
For secondary female sexual characteristics HRT is recommended. This is also essential for protection against osteoporosis and CVD
Fertility options are with IVF and a donor egg
Alternatively adoption remains and option.
Complete Androgen Insensitivity Syndrome (CAIS)
You have a condition called Complete Androgen Insensitivity Syndrome.
MDT
psychology paeds endocrinology
Written information
support groups
The karyotype is XY but a lack of the testosterone receptor
AMH causes regression of the mullerian system therefore there is a lack the uterus. The vagina is relatively shortened
Physiotherapy and vaginal dilators will be needed to help lengthen the vagina for sexual function. If this fails surgical approaches can be considered
There is a 2-3% of developing cancer in the gonads they are secreting testosterone now that is converting to androgen resulting in the secondary sexual characteristics
After puberty surgical removal of the gonads is recommended followed by HRT for bone and cardiovascular health
I would also encourage you to have regular weight-bearing exercise and healthy diet. You will also need to have regular bone density scan to make sure that your bone mass is adequate.
Refer you to a genetic counselling as this is an Autosomal recessive condition in a large proportion of cases. Therefore there is a chance that your sisters could be affected. I would therefore recommend that your sisters have proper counselling with subsequent testing.
Turners
This patient has Turners Syndrome. This is a genetic condition with the karyotype 45X0
Risks
Premature ovarian failure
E deficiency is associated with Osteoporosis and cardiovascular disease
These include cardiac renal endocrine problems and eye and hearing abnormalities. No association with mental impairment
Infertility
Ix
Screen for coexisting abnormality
CXR, ECG, echo, renal USS, TFT, HbAIC, audiology, opthlamology.
Management
MDT including endocrinology and a cardiology review
Liaising with the GP for ongoing management of chronic health condition
Written information and contact for support groups
I recommend maintaining a healthy diet, avoiding smoking excess caffeine or alcohol, and partaking in regular weight bearing exercise.
hormonal replacement therapy until 52 is recommended to balance the above risks
Growth hormone if indicated
if fertility was desired Pregnancy maybe possible with egg donation and IVF but a thorough screen would need to occur to determine the safety of pregnancy depending on other co morbidity
To monitor your ongoing health you will need
Annual
HbAIC / Lipids / TFT / Ophthalmic review / Audiologic testing
Biannual
Echo / Dexa scan
MRKH
Mullerian Agenesis
You have a condition called Mullerian Agenesis or Mayer Rokintansky Kuster Hauser Syndrome.
This is where you have normal sex chromosomes and hormones however an abnormality in the development of you pelvic organs. You have normally functioning ovaries however you do not have a vagina or uterus.
Absence of a vagina means that at this stage you will be unable to have penetrative sexual intercourse. However this can be overcome by the use of physiotherapy and vaginal dilators with good success. Where this is unacceptable or fails surgical methods such as Laparoscopic Vechietti or McIndoe Reid can be used. This will allow you a normal sex life.
As you do not have a uterus you will not get periods and you will not be able to carry a pregnancy. However using assisted reproductive techniques you can have a child via surrogacy. Alternatively adoption remains an option
Finally this condition can be associated with other health issues including skeletal and kidney problems. Therefore I would like to organise a renal USS, IVP, skeletal survey to investigate these further.
I would also like to ask a social worker and psychologist to be involved, to help you and your immediate family to deal with this diagnosis. I would also like to provide you with written information regarding this condition and refer you to a local support group. You are not alone in this condition.
Note - no genetic inheritance patterns of concern
CAH
Congential Adrenal Hyperplasia
Your child has a condition known as Congenital Adrenal Hyperplasia. This is a genetic condition where there is an abnormality with an organ known as the adrenal glands. The adrenal gland produces important hormones including aldosterone which is needed to maintain salt and water balance in the body, cortisol to deal with stress and sugar metabolism, androgens which are a form of male sex hormone.
Congenital adrenal hyperplasia can involve abnormalities in the production in some or all of these hormones. Most commonly we see a deficiency in cortisol and aldosterone and an excess in androgens.
This has significant health implications and your child will be managed under a MDT setting lead by a paediatric endocrinologist. The low cortisol and aldosterone place your child at risk of a life threatening condition called a “salt wasting” crisis (hyponatremia, hyperkalaemia, metabolic acidosis, shock). This can easily be prevented by treating them with a medication called hydrocortisone +/- fludrocortisone so long as it is identified in a timely manner. This treatment will need to be lifelong.
The excess male hormone is a little trickier. These levels will normalise by using the treatment as above. However as your child was exposed to high male hormone levels inside the womb it may be that there are irreversible “male like” changes to the external genital. This is only a problem if they are female and will then generally require surgical correction over the early child hood years.
Finally I would like to refer you to a geneticist as this condition can run in families (autosomal recessive)
Klinefelter Syndrome
Additional X chromosome
XXY. This was most likely a random new error that could have come from either your father or mother.
The presence of the extra X chromosome leads to a relative hypogonadism and testosterone deficiency and wide implications for your health.
Increased length of the long bones with long arms and legs. There is often a degree of breast development (gynaecomastia) and under virilisation with small testes and reduced male pattern facial and body hair.
Commonly the diagnosis is made in fertility clinics as there is reduced sperm count ranging from mild reductions to oligospermia to azoospermia. However conception can be achieved with testicular biopsy, aspiration of sperm, and IVF with ISCI.
We recommend referral to a genetic counsellor as due to the risk of chromosomal imbalance in the offspring. This risk has not been able to be quantified but is thought to be small.
Klinefelters is not associated with significant intellectual impairment however is associated with difficulty in social interactions and deficits in attention and impulsivity and linguistics.
It can be associated with medical conditions
Pulmonary diseases - chronic bronchitis, bronchiectasis, emphysema
Cancers - germ cell tumours, breast cancer, non hodgkins lymphoma
Varicose veins and leg ulcers
SLE
Diabetes mellitus
Treatment is largely based around male hormone replacement with testosterone to maintain normal male secondary sexual characteristics, provide virilisation, and improve psychosocial interactions. It will not improve sperm count.
Recurrence risk is not above that of the general population
Ambiguous Genitalia
Your baby is gorgeous. However I have been asked to come and see you as it appears there is uncertainty regarding the genitalia. I would like to ask you some questions and then together examine your baby. Is that okay with you?
History - drugs in pregnancy, consanguinity, or family hx of ambiguous genitalia, IUD/NND, hyperandrogenism, congenital abnormalities
Exam - vital signs, evidence of dehydration (fontanelles), head to toe examination, genital examination looking a urethral meatus / vagina / labial folds / clitoris / gonads / phallus / groin
Your baby has genitalia that don’t appear clearly male or female. Whether we develop into a male or female gender depends on the presence of our chromosomes, hormones, and hormone receptors. Chromosomes are the genetic building blocks that make up who we are. Male gender is typically associated with XY and female XX. However we also need the presence the corresponding male or female sex hormone, and the ability of our body to process and recognise this. Ambiguous genitalia can result from a range of conditions affecting our chromosomes, our production or sex hormones, or our ability to recognise these sex hormones.
I would like to organise some urgent tests. I would recommend delaying assigning a sex to the baby, naming the baby, or registering the birth until we get the results of these tests back. The aim of these tests is to ensure there are no immediate health concerns for the baby, and secondarily determine what the genetic gender is, and why there has been problems with the development of the external genitalia.
These tests include: FBC, UEC, LFT, karyotype, SRY gene (FISH specific probes), AMH, 17 OHP, testosterone, DHEAS, androstenedione, cortisol, dihydrotestosterone, FSH, LH, USS abdomen and pelvis
This is a very distressing diagnosis and I would like to refer you to a social worker and psychologist to help you cope at this time. I would like to direct you to local support groups to talk to other families who understand what you are going through.
We will have a whole team all devoted to looking after you and your baby including paediatrician, psychologist, endocrinologist, paediatric surgeon, social work. Please ask questions or for help at any time.
Where there is a genetic basis to the causative condition I would also refer you to a geneticist to discuss the implications and consider testing of others in the family.
CAUSES: CAH (AR), 5 alpha reductase deficiency (AR - conversion testosterone to DHT), tumours, maternal hormones in pregnancy, androgen insensitivity syndrome (AR)
FRAGILE X
You have a genetic condition called Fragile X. It is a condition with abnormalities on the X chromosome which is a sex chromosome.
This is an X-linked condition whereby females are carriers and males are affected. A male has a 50% chance of inheriting it from his mother and will not inherit it from his father. A female has a 50% chance of inheriting it from her mother or 100% chance from her father - she will be a carrier.
Fragile X can be inherited as a pre mutation, or the full mutation. Where or not it is a pre mutation or the full mutation is related to the number of repeats….this tends to increase with each round of inheritance. The full mutation is defined as >200 CGG repeats.
In the premutation form it is associated with premature ovarian failure in female carriers (~20-25% risk), and adult onset tremor / ataxia syndrome for both males and females (only in a small number, onset >50yrs, males>females).
In the full mutation form females are generally unaffected and males can be affected as below.
Males who are affected have a range of symptoms including physical features, medical problems, and neurodevelopmental and intellectual delays.
Physical features include a long face with large prominent ears, hyperextensible joints, low muscle tone, flat feet, and large testes.
Medical problems include seizures / epilepsy (~24%), and anxiety and unstable mood
Neurodevelopmental problems include mild to severe intellectual disability, ADHB, autism, speech delay
As this is a genetic condition we recommend genetic counselling to all carriers or affected individuals for their pre existing families and would also offer PGID and IVF as an option if wishing to have their own family to eliminate the risk to their children.
