Achondroplasia

AHMG Fall 2004

Juniata College
Normal Growth
 Final adult stature is at least 80% genetic---
POLYGENIC
 Birth length~20”
 Growth
 1st year~10”
 2nd year~5”
 Thereafter 2.5” per year until puberty
 Final adult height
 Mid-parental height +2” for boys and -2” for girls
Short stature
Normal or variant Pathologic short
short stature stature
 Short stature
Normal or variant Pathologic short
short stature stature

Genetic short Constitutional

stature delay: (i.e. “late
bloomer”) keep
growing when
others stop
Short stature
Normal or variant Pathologic short
short stature stature

Disproportionate Proportionate short

short stature: ex: stature: ex: endocrine
skeletal dysplasia problems, Down
Syndrome
Metabolic bone disease
“Midget”
“Dwarf”
Disproportionate short
stature: diagnosis
 Upper/lower ratio (head to hip socket is
upper)
 ~1.7 at birth
 ~0.95 caucasian adult/~0.85 Af. Am. Adult
 Span (fingertip to fingertip)
 Equals height up to adolescence
 After, up to 5 cm>height
 X-rays are diagnostic for skeletal dysplasias
For general characterization
 Compare
 Chronological age
 Height age (height of a person at the 50th
percentile for their age)
 Bone age (ossification assessed by X-ray)
 If:
 BA=CA, genetic short stature
 BA=HA, constitutional delay
 BA<HA, pathologic short stature
Achondroplasia
 AD; 1/15,000
 Defect in FGFR3; 4p16
 Most common non-
lethal Sk. Dys.
 80% new mutations
 Macrocephaly with
midface hypoplasia
 Rhizomelic limb
shortening
 Normal intelligence,
usually

Jorde et al. Medical Genetics. 2nd edition.

Hypochondroplasia
 Also caused by
mutations in FGFR3;
milder than
achrondroplasia
 AD; 1/25,000
 Macrocephaly; limb
shortening
 Adult height 4.5-5.0 ft.
 Normal intelligence
Thanatophoric dysplasia
 Mutations in the FGFR3
gene
 AD; 1/25,000
 Lethal skeletal dysplasia
 More severely affected
with same phenotype as
achondroplasia
 Also, narrow chest with
short ribs/”telephone
receiver” femurs/flat
vertebrae
http://zygote.swarthmore.edu/cell7.html
Other causes of short stature
 X-linked hypophosphotemic rickets
 X-linked dominant (males more severely affected)
(disproportionate)
 Turner Syndrome (45,X) (proportionate)
 Laron Dwarfism
 Insensitivity to growth hormone (receptor
defect)/AR/proportionate S.S./squeaky voice
 Malnutrition
 Chronic disease
 Other endocrine problems