Syndromes Flashcards
Turner syndrome - what is the cause of the short stature
SHOX haploinsufficiency
Features of Turner syndrome
Cubitus valgus,
shortened 4th metacarpals,
webbed neck,
high arched palate,
scoliosis,
Madelung deformity,
neurosensory hearing loss,
horseshoe kidney,
left sided heart defects (coarctation of aorta and/or bicuspid aortic value),
difficulty in visual-spatial tasks, math;
excel in reading
Short stature
what is the usual final height of someone w Turners syndrome
8-10 cm below MPH
What is the ovarian function in turner
varying degrees
labs: primary hypogonadism
Malignant transformation in gonads of persons with Y chromosome material
Those w Turner sydrome have higher risk fo?
Higher risk for autoimmune thyroiditis, celiac disease, T1DM
Turner syndrome: treatment w GH
- when to start
- what is the expected benefit
Recommendation to start at 4-6 years of age
Gain of 5-8 cm over 5.5-7.5 years of treatment.
0.3-0.35 mg/kg/week
can add oxandrolone 0.03-0.5mg/kg/day from age 10 years if dx is delayed or if adult height outcome is likely to be unsatisfactory
- works by increasing IGF-1
Turner syndrome: treatment w estrogen
- when to start
- what to use
- how to progress
Ideally start between 11-12 yo.
Systemic estradiol (transdermal»oral). Start low, go slow (reaching adult dose 2-3 years later).
No Equine Estrogens! (Premarin)
Add progesterone once vaginal bleeding commences or after 2 years
what other specialities should follow turner syndrome
cardiology, audiology, developmental pediatrician
what is the incidence of Turner syndrome
1 in 2000
Klinefelter syndrome - what is height due to
Tall stature due to higher SHOX gene dosage
features of klinefelter
Cryptorchidism,
micropenis,
learning disability,
behavior difficulties/impulse control,
speech delay,
varying degrees of testicular function gynoid body habitus,
gynecomastia,
pubertal development may be stalled
Small, firm testes
Hormone pattern is primary hypogonadism
Klinefelter: what are they at higher risk of
breast cancer,
T2DM,
metabolic syndrome
germ cell (HCG secreting) tumors
osteoporosis
Klinefelter - when to start Testo
what to target
Controversial on how early to start
when LH/FSH high? vs ?when testosterone levels low for age/puberty stage
*Intratesticular testosterone necessary for spermatogenesis -> postpone T treatment until after sperm collection
Once treatment decided, agreed to target testosterone levels in mid-normal range for age.
Normalization of LH may or may not be achieved
McCune Albright Syndrome
- main features
1) Gonadotropin Independent (peripheral ) precocious puberty
2) Café-Au-Lait: large, “Coast of Maine”
3) Fibrous Dysplasia of Bone
4) Endocrine dysfunction in other Hormone Receptors that use G protein Gsα signaling cascade
- TSH receptor – hyperthyroidism
- ACTH receptor – Cushing syndrome
- GHRH receptor – GH excess
- PTH receptor – hyperparathyroidism
PRL excess
McCune Albright Syndrome - gene and what it does
GNAS gene is imprinted – mutation variably present in tissues; may not be present in blood sample
activating mutation of the alpha subunit of the G protein receptor
constitutive activation of adenylyl cyclase and up regulation of cAMP in absence of ligand interaction with the receptor
McCune Albright Syndrome
- how to treat precocious puberty
Ketoconazole – Increases sex steroid metabolism via liver induction of P450 enzymes
Tamoxifen - Estrogen receptor modulator
boys: androgen receptor blocker and aromatase inhibitor
McCune Albright Syndrome
- how to treat the fibrous dysplasia
supportive
?denausomab
Bardet-Biedl Syndrome- features
obesity,
short stature,
mental retardation,
kidney dysfunction,
polydactyly,
retinitis pigmentosa
**progressive vision loss due to retinal deterioration, multicystic kidney dysplasia, polydactyly, gait and coordination impairment, intellectual disability
Hypogonadotropic hypogonadism and primary hypogonadism have been reported
Smith-Lemli-Opitz Syndrome
- what is It
an autosomal recessive defect in cholesterol biosynthesis resulting from abnormalities in the sterol Δ-7-reductase gene, DHCR7
Smith-Lemli-Opitz Syndrome
features
microcephaly,
developmental delay,
typical facial appearance (short nose with broad nasal bridge and anteverted nares, long philtrum, microretrognathia, blepharoptosis, low- set, posterior-rotated ears, cleft and/or high-arched palate),
proximal thumbs,
syndactyly of the second and third toes
Cardiac, renal, lung, and gastrointestinal abnormalities
Genital anomalies include hypospadias, cryptorchidism, and even ambiguous genitalia in males.
Adrenal insufficiency is present in some cases, especially during times of stress or when LDL-derived cholesterol sources are inadequate (e.g., dietary insufficiency/bile salt depletion)
what are the genital anomalies in SLO
Genital anomalies include hypospadias, cryptorchidism, and even ambiguous genitalia in males.
what to do if a pt with Turners wants to get pregnant
First two are the main ones:
i) Imaging of the thoracic aorta and heart with a transthoracic echocardiography (TTE) and CT/cardiac magnetic resonance scan (CMR) within 2 years before planned pregnancy to look for aortic dilatation. TEE should be done again at 20 weeks gestation to look for aortic dilatation
ii) Blood pressure monitoring for hypertension. Conservative goal of BP under 135/85. Recommended exercise testing prior to pregnancy to reveal exercise induced hypertension.
iii) Thyroid function to look for hypothyroidism
iv) A1C or fasting glucose to screen for diabetes
v) Liver enzymes to look for transaminitis
v) Uterus ultrasound: they are often not fully mature and can lead to fertility complications and inability
vi) LH/FSH and estrogen to look for primary ovarian failure
vii) AMH and Inhibin B to look for ovarian reserve
Kallman syndrome gene
inactivating (prokinectin receptor 2)
● Mutation in a receptor involved in the signalling pathway of anosmin (which guides axonal development of the GnRH and olfactory neurons)
comorbidities in turner syndrome
- hypertension
- hypothyroidism
- T1DM/T2DM
- Dyslipidemia
- Celiac disease
- Vit D def
- renal anomalies
- nevi
- low BMD
- Coarctation and aortic root dilation
- SNHL and CHL
- scoliosis
- Psych – poor visuospatial and arithmetic