1 Peds Genetics Flashcards
What’s the real name for “brittle bone disease”?
Osteogenesis Imperfecta
What type of genetic disease is OI?
Autosomal dominant mostly
Some autosomal recessive subtypes
Majority of cases of OI involve mutations in what genes?
Alpha-1 and alpha-2 chains of TYPE I COLLAGEN (COLA1 or COLA2)
Which subtype of OI is the most common?
Type I
It’s mild. Sometimes you wouldn’t even know by looking at them that they’s got fucked up bones.
Which subtype of OI is the most severe?
Type II
Usually lethal in utero
How many other subtypes of OI are there?
Types III-IX: Moderate-severe with characteristics of everything in between
Key clinical features of osteogenesis imperfecta
Excessive/atypical fractures*** Short stature Bowlegs or other limb deformities Scoliosis/kyphosis*** (more common with Type III-IX, can lead to breathing difficulties) Basilar skull deformities —> spinal cord concerns BLUE SCLERAE****************** Hearing loss (progressive)*** Opalescent teeth*** Ligament and skin laxity
What are the dental findings in OI called?
Dentinogenesis imperfecta
Opalescent teeth
What is a common imaging modality for early diagnosis of OI?
Maternal U/S if severe
Fractures at various stages of healing that may be misdiagnosed as child abuse
Osteogenesis imperfecta
What are some hallmark imagining findings suggestive of OI?
Wormian bones (suture bones of skull)
Codfish vertebrae (vertebral bodies bi-concave from compression fractures)
Osteopenia
Why might you skip f/u xrays for a simple fracture in a kid with OI?
To minimize radiation exposure
How is OI usually diagnosed?
Often it’s a clinical diagnosis, especially if family history (unless you want to determine the specific subtype)
What does biochemical testing do for us in OI?
Helps evaluate structure and quality of type I collagen
Common lab findings in OI
Vitamin D, phosphorus, alkaline phosphates may be normal or elevated with recent fracture
HYPERCALCEMIA is common and relates to severity (b/c bones constantly being remodeled)
What is the main medicinal treatment for OI?
Bisphosphonates - Pamidronate (IV infusion every 3 months: 4 hours daily for 3 days)
Slows down bone reabsorption —> reduces fracture rates and increases bone density
Risks of hypocalcemia, OSTEONECROSIS OF THE JAW, and nephrotoxicity. But it’s helpful, I guess.
Marfan syndrome is a genetic mutation in …
Connective tissue protein FBN1 (fibrillin)
Autosomal dominant
Cardiac effects of Marfan syndrome
AORTIC ROOT DILATION/DISSECTION**
—> Aortic rupture risk
Mitral valve prolapse
What pulmonary condition are Marfan patients more predisposed to experience?
Spontaneous pneumothorax
What are the ophthalmologic effects of Marfan syndrome?
Myopia (nearsightedness)
Lens subluxation/dislocation
Musculoskeletal presentation of Marfan syndrome
Tall, thin with increased arm span/ht ratio
SCOLIOSIS
ARACHNODACTYLY (look for positive hand signs)
Pectus deformity
Hind foot valgus
Hyper mobile joints with laxity
Steinberg sign
Used for clinical evaluation of Marfan patients
Fold your thumb into the closed fist. Test is positive if the thumb tip extends from the palm of the hand.
Walker-Murdoch sign
Used for clinical evaluation of Marfan patients
Grip your wrist with your opposite hand. If thumb and fifth finger of the hand overlap with each other, this represents a positive test.
How is marfan diagnosed?
CVS or amniocentesis may detect defective gene
DNA testing