Syndromic Growth Disorders and Short Stature

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