Genetics - Ehler Danlos Syndrome, Prader Wili, Klinefelder Flashcards
Ehler Danlos Major Criteria (5)
a. Assessment
b. Hyperextensibility
c. Widened atropic scars = Tissue fragility
d. Joint hypermobility
e. One or more are required for diagnosis
Ehler Danlos Minor Criteria (7)
a. Smooth velvety skin
b. Molluscoid pseudotumors
c. Complication of joint hypermobility
d. Easy bruising
e. Muscle hypotonia
f. Signs of tissue extensibility and fragility
g. Positive family history
Ehler Danlos Types (6)
- Classical
- Hypermobility
- Vascular Type
Less common
- Kyphoscoliosis type
- Arthrochalasia type
- Dermatosparaxis type
Ehler Danlos Cutaneous Fragility (3)
- Easy splitting of the skin is particularly common in Classical Type (Types l and ll).
- Gaping, ‘fish-mouth’ or ‘cigarette paper’ scars follow
- With Minimal trauma over sites of bony prominence and areas prone to trauma such as the forehead, chin, elbows, knees and shin, thin scars result
Ehler Danlos Characteristics (11)
- Easy bruising, at sites of trauma, accompanies most forms of EDS.
- Increased fragility of dermal blood capillaries and poor structural integrity of the skin.
- When bruising presents in a child it may be incorrectly attributed to non-accidental injury.
- Fatigue
- MITRAL VALVE PROLAPSE.
- Rupture. Arterial/uterine/intestinal due to tissue fragility.
- Hernias
- Scoliosis
- Gum disease.
- Gastrointestinal diverticula
- Molluscoid pseudotumours – firm, fibrous lumps measuring up to 2 - 3 cm which develop over pressure points such as the elbows and knees.
Ehler Danlos Joints (4)
- Hypermobility should be assessed using the Brighton scale. A score of 5/9 or defines hypermobility.
- Dislocation and subluxation.
- Chronic joint and limb pain.
- Pain is common even when skeletal X-Rays are normal.
Ehler Danlos: Brighton Scale (5)
(5 out of 9 = joint hypermobility)
- Passive dorsiflexion of little finger beyond 90 degrees (one point for each)
- Passive apposition of thumbs to flexor aspect of forearm (one point for each)
- Hyperextension of the elbows beyond 10 degrees (one point for each elbow)
- Hyperextension of knees beyond 10 degrees (one point for each knee)
- Forward flexion of the trunk with knees fully extended so that palms can rest on the floor (one point)
Prader-Willi Overview (5)
- Prader-Willi is caused by a failure of expression of the paternally acquired imprinted region on chromosome 15q11- q13 that results in a recognizable set of signs and symptoms that affect the neurological and endocrine systems.
- Characterized by voracious, uncontrollable appetite and obesity
- Presents with failure to thrive in infancy and then has a varatious appetite
- It equally affects both sexes and has equal worldwide incidence
- 1:15,000 to 1:25,000 incidence (The Committee on Genetics, 2011)
Ehler Danlos: Signs and Symptoms of Prader-Willi Syndrome (6)
- In infancy, the child has hypotonia, failure to thrive, and early feeding problems.
- Later, hyperphagia (voracious appetite) develops with characteristic behavioral problems and global developmental delay.
- Behavioral problems include temper tantrums and obsessive-compulsive disorders including skin picking, stubbornness, perseverant speech, psychosis.
i. Very difficult to manage; stubborn, tantrums, etc.
ii. Drugs to control this also causes a lot of weight gain so they aren’t good for these children
iii. Behavior issues are the biggest problem - Sleep apnea with hypoventilation, excessive daytime sleepiness and early-morning walking
- Hypernasal speech with a weak or squeaky cry during infancy
- Temperature instability with high pain threshold
i. Can walk around with broken bones and not care
Ehler Danlos Physical Exam (6)
- Growth: Short stature, failure to thrive in infancy, obesity
- Face: Dolichocephaly, narrow bitemporal diameter, almond shaped up slanting palpebral fissures, strabismus, nystagmus, myopia, hyperopia, thin, upper lip, small mouth with downturned corners and thick viscous saliva
* Characteristic almond shaped eyes - GU: Small genitalia, Cryptorchidism
- Skin: Hypopigmented,blondetobrownhair, frontal hair upsweep
- Orthopedics: Osteoporosis, kyphosis, small hands and feet, clinodactyly, Narrow hands with straight ulnar border, scoliosis
- Neurological: Poor fine and gross motor skills, mild to moderate Mental retardation, in the neonatal period there is a poor suck and swallow with feeding problems
Primary Care Management of the Child with Prader-Willi (4)
FISH study to look at the PWS region—
(1) In 70%, the paternally inherited chromosome 15 has microdeletions of 3-4 megabases of genetic material in the PWS region
(2) In around 20%, the child acquired two copies from the mother and none from the father
(3) In around 5%, there is a defect in the process of imprinting in when the father passes on the region he received from his mother
(4) A balanced translocation that moves the imprinting center away from the correct region.
Follow-Ups and Referrals with Prader-Willi (8)
- Orthopedics, dental, endocrine, ophthalmology, dietician evaluations
- Growth hormone deficiency frequent, but not universal
- Thyroid screening with TSH every 2-3 years.
- Behavioral therapy for control of eating and other problem behaviors
- Genetic counseling
- Early intervention and appropriate school placement with supports
- Psychosocial support for child and family
- Refer to endocrinology for evaluation and management of growth hormone deficiency
Children with Prader Willi – Parental Education (7)
- Need for follow up with specialists, dietary management
- Patients have a high pain tolerance,
- Increased risk of febrile seizures (5-10%)
- High rates of obstructive sleep apnea, behavioral management skills
- Family adjustment
- Family planning methods as the child ages
- Support Groups
Klinefelter Overview (3)
- Klinefelter syndrome is the most common sex chromosome disorder in males with 47,XXY karyotype or a variant with an estimated frequency of 1:660 male newborn
- Extra X chromosome can come from either parent
- Linked to advanced maternal age; men with mosaicism are less affected and tend to go undiagnosed until later in life.
Klinefelter Genetics (4)
- Maternal meiotic nondisjunction resulting in contribution of two X chromosomes to maternal zygote (ova)
- When ova is fertilized by sperm containing one Y chromosome, resulting embryo has Klinefelter karyotype
- Most common numerical chromosomal aberration is double X and a Y
- Most common cause of hypogonadism and infertility in men
