18 Questions
What is a syndrome?
A group of signs and symptoms that occur together and characterize a particular abnormality or condition
What is the most common chromosomal cause of short stature?
Down syndrome
What is the genetic defect in Turner syndrome?
Absence of one X chromosome or a chromosome with a short arm
What is the name of the gene responsible for achondroplasia?
FGFR3
What is the effect of vosoritide on achondroplasia?
It has a positive effect on growth and possibly on spinal stenosis
What is the definition of tall stature?
Height > 2 SDS
What is the name of the receptor affected in achondroplasia?
Fibroblast growth factor receptor 3
What is the difference between syndromic and non-syndromic growth disorders?
Syndromic disorders have multiple symptoms, non-syndromic have only short stature
What is the definition of short stature?
Height > 1.6 SDS under target height
What is the effect of a mutation in the FGFR3 gene?
Constant growth inhibition
What is the mechanism of action of vosoritide in the treatment of achondroplasia?
It inhibits the inhibiting effect of the FGFR3 receptor
What is the risk of a child having achondroplasia if one parent has the condition?
50%
What is the characteristic feature of Leri-Weil dyschondrosteosis?
Short arms and legs, with muscle hypertrophy
What is the location of the SHOX gene, which is mutated in Leri-Weil dyschondrosteosis?
Pseudo-autosomal region of X and Y chromosomes
What is the key feature of syndromic growth disorders?
Short stature with additional clinical features
What is the importance of DNA analysis in making a diagnosis of syndromic growth disorders?
It is not always necessary
What is the definition of short stature?
Height below 3 SD
What is the inheritance pattern of achondroplasia?
Autosomal dominant
Study Notes
Tall Stature
- Tall stature is defined as a height > 2 SDS (standard deviation) or > 1.6 SDS above target height based on parent's height
- Tall stature differs from overgrowth, which refers to excessive growth in specific areas of the body
Short Stature
- Short stature is defined as a height < -2 SDS or > 1.6 SDS under target height based on parent's height
- Height is measured in standing position, while length is measured in a lying down position, typically for newborns
- Short stature can be classified into syndromic and non-syndromic growth disorders
Measuring Guidelines
- Measure patients' heights, weights, head circumference, armspan, and sitting height
- Measure parents' heights, armspan, and sitting height when necessary
- Height is influenced by 60-80% genetic factors, with feeding, health, and medication also playing important roles
Syndrome Definition
- A syndrome is a group of signs and symptoms that occur together and characterize a particular abnormality or condition
- Syndrome identification involves pattern recognition
- There are 1568 syndromes with short stature, and 320 syndromes with short stature and disproportion
Causes of Short Stature
- Primary growth disorders: syndromes, SGA (small for gestational age) without catch-up growth, skeletal dysplasia, and disorders of bone metabolism
- Secondary growth disorders: malnutrition, celiac disease, hormonal disorders, and metabolic disorders
- Idiopathic short stature, where the cause is unknown
Turner Syndrome
- Occurs only in girls, with a frequency of 1:2,500
- Characterized by a missing or partially deleted X chromosome
- Symptoms: short stature, heart condition, infertility, and may benefit from growth hormone therapy
Noonan Syndrome
- Caused by a gene mutation, occurring in both boys and girls
- Symptoms: short stature, developmental delay, facial features (hypertelorism, ptosis, low-set ears, broad neck), congenital cardiac anomaly, pectus deformity, lymphatic abnormalities, coagulation defect, and cryptorchidism
- Genetic mutations occur in the RAS-MAPK pathway, with PTPN11 being the most common mutation (50%)
- May benefit from growth hormone therapy
Skeletal Dysplasia
- Frequency: 1:3,000 live births, and 1:110 perinatal mortality
- Characterized by abnormalities in epiphysis, metaphysis, and/or diaphysis
- Often causes disproportionate short stature
- Heterogeneity in clinical and genetic features
Achondroplasia
- Frequency: 1:15,000 to 1:40,000
- Clinical features: short stature, large head, short arms and legs, skin creases, pronounced lumbar lordosis, deep nasal bridge, frontal bossing, and short hands with trident
- X-ray features: narrowed interpedicular distance in the lumbar spine
- Treatment: symptomatic, with growth hormone not effective; limb lengthening and decompression spinal stenosis may be considered
- Vosoritide is a novel treatment that has a positive effect on growth and possibly spinal stenosis
FGFR3 Gene
- Located on chromosome 4, mutations cause achondroplasia
- Mutations are usually de novo, with a 50% chance of inheritance if one parent is affected
- Genotype-phenotype correlation: autosomal dominant inheritance
Leri-Weil Dyschondrosteosis (LWD)
- Frequency: unknown
- Clinical features: short stature, short arms and legs, Madelung deformity, muscle hypertrophy, and short 4th metacarpal bone
- Growth hormone therapy is effective
- Genetics: mutations in the SHOX gene, located in the pseudo-autosomal region 1
Importance of Recognition
- Recognition of syndromic growth disorder is crucial for diagnosis and management
- Measurement and description of clinical features are essential for diagnosis
- DNA analysis is not always necessary for diagnosis
- Understanding the inheritance pattern is important for patient and family counseling
This quiz assesses your understanding of syndromic and non-syndromic growth disorders, specifically short stature, and their clinical features, molecular background, and inheritance patterns.
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