Short Stature Flashcards
How do we define short stature?
Growing 2 SD below the mean (<2.3 %ile)
* Extrapolation to adults: 4’11” for women, 5’3” for men
* Varies by sex and ethnicity
What are factors that influence height?
- Social: Poor nutrition (weight percentile lower than height)
- Vitamin D deficiency: Sunlight and supplements
- Endocrine: Growth hormone deficiency, hypothyroidism
- Chronic disorders:
-Anemia, renal disease, inflammatory bowl disease (Crohns), juvenile
idiopathic arthritis, heart disease, chronic diarrhea - Genetic disorders
-Chromosomal (trisomy 21), cystic fibrosis, developmental disorders (Kabuki,
Cornelia de Lange, and a very long list of others)
What does growth arrest imply?
New onset hormone deficiency or medical disorder
How do you access bone age?
- Hand films most common
- Or, X-ray films to count growth centers from half the body—more accurate, but less used
What is the definition of a skeletal dysplasia?
- Disproportionate bones
- Short segments of limbs
- Abnormal upper:lower segment ratio
-Lower segment = long bones, upper = spine and head
-Sitting Height - Disproportionate head size in some
You have a patient with the following:
* Short stature with rhizomelia
* Macrocephaly
* Facial changes: Bossing, midface retrusion
* Exaggerated lordosis, gibbus
* Limited Extension of the arms
* Brachydactyly / trident hands
What do you suspect?
Achondroplasia
What does rhizomelia mean?
“Rhizo”= root
Shortening of the bones in the upper arms and thighs
What does “Acro” mean?
“Acro” = tip
What are complications of Achondroplasia?
- Narrow craniocervical junction can compress the spinal cord
-Hydrocephalus
-Spasticity
-Bladder/bowel disorders
-Apnea –> Death in 7.5%, untreated - Low tone and motor delay, especially with head control
- Restrictive lung disease
- Sleep apnea
- Ear infections
- Spinal complications: Kyphosis, lordosis, spinal stenosis
- Intelligence: normal, if no CNS complication
What are the Screening/interventions for Achondroplasia?
- MRI of the brain at diagnosis
- CT of the spine at diagnosis
- Sleep study at diagnosis
-May need tonsils out or CPAP - If the above abnormal, may need decompression surgery
- Orthopedic evaluation for bowing of legs
- Prevention of kyphosis through positioning and back support
What is the most common mutation causing Achondroplasia?
99% have one of two pathogenic variants in FGFR3:
* c.1138G>A p.Gly380Arg
* c.1138G>C p.Gly380Arg
What percentage of Achondroplasia is de novo?
80% de novo
What are the disorders caused by FGFR3 mutations?
- Achondroplasia
- Hypochondroplasia
- Thanatophoric dysplasia
- Crouzon
- Muenke
What is the result of Homozygous achondroplasia?
Usually causes respiratory insufficiency and neonatal death
How is Hypochondroplasia different from achondroplasia?
- Lack of rhizomelia / brachydactyly
- Craniofacial findings subtle or absent
- Head size more proportional
What is the phenotype of Hypochondroplasia?
- Other changes in FGFR3
- Milder short stature
- CNS issues more prominent
- Seizures, developmental delay
What kind of skeletal dysplasia is characterized by:
* Respiratory insufficiency
* “Telephone receiver” femurs
* Often identified by prenatal ultrasound
-“Short long bones”
Thanatophoric dysplasia
What is the phenotype of Campomelic Dysplasia “Bent limb”?
- Autosomal dominant, SOX9
- Distinctive facies
- Pierre Robin sequence with cleft palate
- Shortening and bowing of long bones, and clubfeet
- Laryngotracheomalacia with respiratory compromise—often lethal
- Ambiguous genitalia or 46,XY sex reversal
What are the characteristics shared between Osteogenesis Imperfecta Types I and IV?
- Multiple fractures, minimal trauma
-Type I often improves over time - Short stature
- Blue or gray sclerae (whites of eyes)
- Weak teeth (dentinogenesis imperfecta)
- Progressive, postpubertal hearing loss
- Loose joints
- Low bone density
- Wormian bones
- Often evaluated non-accidental trauma cases
What are the eye findings in OI Types I and IV?
- Type I: Blue sclerae, mild
- Type IV: Gray or normal sclerae, mild-moderate
What is the phenotype of OI Type II?
- Perinatal lethal. 60% die on day 1, 80% die by 1 week, survival past 1 year very rare
- Respiratory distress/insufficient aeration due to small rib cage
- Dark blue sclerae
- Extremities short, bowed
- Thin skull, wide fontanelle
- X-rays show “crumpled” long bones and multiple fractures
- More recent recessive forms
What is the phenotype of OI Type III?
- Progressive deforming
- Can have fractures from newborn handling
- Over 200 fractures in a lifetime common
- Bones progressively change even without fractures—70 to 90 degree angulation
- Short stature common
- Often require wheelchair
What are the Intervention / screening / treatment for OI?
- Orthopedic referral
- PT/OT
- If neurologic signs, CT scan for basilar impression
- Bisphosphonate infusions lead to stronger bones
-Does not decrease risk of fracture
-Now fractures occur with higher stress - Family testing/tracing
What is the phenotype of Stickler syndrome?
- Micrognathia with Pierre Robin
- High myopia – leading to retinal detachment
- Hearing Loss
- Hypermobility
- Epiphyseal dysplasia – arthritis
- Short stature
What genes cause Stickler syndrome?
- COL2A1. Autosomal dominant
- Also, COL11A1, COL11A2 (AD), COL9A1, COL9A2, COL9A3 (AR)
What are the facial features of Stickler syndrome?
Malar flattening
Flattened nasal bridge
What are the treatments/screening for Stickler syndrome?
- Orthopedics
- Ophthalmology—protect retina with cryotherapy
- Audiology for hearing loss
You have a child that presents with Macrocephaly, Wide anterior fontanel, Short stature, Absent clavicles, and Abnormal dentition. What do you suspect?
Cleidocranial Dysplasia
What is the genetic cause of Cleidocranial Dysplasia?
Loss of function alleles of the RUNX2 gene
What is an interesting fact about SHOX deletion (Leri-Weill)?
SHOX is in the pseudoautosomal region
* Deletion or loss of function can be passed on as X-linked or Y-linked!
What is a Madelung deformity and where do you see it?
A rare arm condition that affects the growth plate of the radius, a bone in the forearm.
SHOX deletion (Leri-Weill)
What causes Langer Mesomelic Dysplasia?
Homozygous loss of SHOX
What are cardiac defects seen in Noonan Syndrome?
Congenital Heart defect (50-80%)
* Pulmonic valve stenosis (20-50%)
* Hypertrophic Cardiomyopathy (20-30%)
What are the features of Noonan Syndrome?
- RASopathy
- Short stature
- Macrocephaly
- Congenital Heart defect (50-80%)
- Pectus excavatum
- Webbed neck
- Craniofacial: Downslanting palpebral fissures, low set posteriorly rotated ears
- ¼ with mild intellectual disability
- Cryptorchidism
- Bleeding defects
- Predisposition to juvenile myelomonocytic leukemia (JMML) with specific mutations
What are the features of Cardiofaciocutaneous syndrome?
- “Neuroectodermal Noonan”
- BRAF, MAP2K1, MAP2K2, KRAS
- Heart issues similar to Noonan
- Dry skin issues—hyperkeratosis, eczema,
ichthyosis - Sparse eyelashes/eyebrows
- Sparse hair but curly, wooly, brittle
- Neurologic problems: Dev delay,
seizures, abnormal MRI
What are the features of Costello syndrome?
- “Noonan syndrome-cutis laxa”
- Loose, soft skin
- Papilloma of face and perianal region
- Joint laxity
- Hypertrophic cardiomyopathy
- Arrhythmia
- HRAS
- Solid tumors
-rhabdomyosarcoma and neurblastoma
-Transitional cell carcinoma of bladder
