Syndromic Short Stature ✅ Flashcards
What are the most common syndromic causes of short stature?
- Russell-Silver syndrome
- Fetal alcohol spectrum disorder
- Turner’s syndrome
- Noonan’s syndrome
- Skeletal dysplasias
What kind of genetic disease is Russell-Silver syndrome?
Imprinting disease
What is the genetic cause of Russell-Silver syndrome?
Maternal uniparental disomy of chromosome 7
What are imprinting disorders asssociated with?
Assisted reproductive techniques
What do imprinting disorders often cause?
Abnormalities of growth
What is Russell-Silver syndrome characterised by?
- Intrauterine growth restriction
- Increased risk of hypoglycaemia
- Sweating
- Asymmetry (one side of the body being shorter than the other)
- Short stature with failure to catch up growth
- Thinness
- Triangular shaped face with small pointed chin and clinodactyly
What does treatment of Russell-Silver syndrome involve?
Optimal dietary support and for some, GH therapy
What problems can alcohol exposure in utero cause?
- Impaired growth
- Brain damage leading to poor concentration, behaviour and learning difficulties
- Characteristic facial appearance of microcephalic, flat mid-face, low-set ears, and micrognathia
What is the genetic cause of Turner’s syndrome?
Loss or abnormality of one X chromosome
What is the incidence of Turners syndrome?
1 in 2500 girls
Why is the phenotype of Turners syndrome fairly mild for such as major chromosomal anomaly?
Reflects partial inactivation of the second X chromosome from early fetal life
What % of conceptions with Turners syndrome result in miscarriage or stillbirth?
99%
What are the characteristic features of Turner’s syndrome?
- Skeletal dysplasia causing short stature
- Short 4th and 5th metacarpals
- Cubitus values
- Micrognathia
- Ovarian failure leading to pubertal failure and infertility
- Lymphoedema
- Neck webbing
- Low hairline and increased naevi
- Congenital heart disease
- Wide spaced nipples
- Madelung deformity
- Middle ear problems
- Renal anomalies
- Specific learning difficulties related to numeracy and visuospatial tasks
- Social vulnerability
- Increased risk of autoimmune and inflammatory disease
What congenital heart disease is particularly common in Turner’s syndrome?
Coarctation of the aorta
What is Madelung deformity?
A focal dysplasia of the distal radial physis
Don’t understand this so work it out later
About 1/3 of the genes on the short arm (Xp) are unsilenced, including the short stature homeobox (SHOX)
Spare card
Spare card
How is the presentation of Turner’s syndrome variable?
Many children with Turner’s syndrome have few abnormal findings
What is the result of many children with Turner’s syndrome having few abnormal findings?
Karyotyping is essential in any girl with impaired growth of unknown aetiology
What is the treatment of Turners syndrome?
- GH therapy to improve growth
- Oestrogen induction of puberty
- Specific monitoring for cardiac, renal, autoimmune, and hearing abnormalities
What is the incidence of Noonan’s syndrome?
1 in 1000
What causes Noonan’s syndrome?
Mutations of genes involved in the RAS/MAPK signalling pathway
What genes involved in the RAS/MAPK signalling pathway are affected in Noonan’s syndrome?
- PTPN11
- SOS1
- KRAS
- RAF-1
What is the inheritance of Noonan’s syndrome?
Autosomal dominant
What are the clinical features of Noonans syndrome?
- Short stature
- Scoliosis
- Low-set ears
- Ptosis
- Pectus excavatum
- Cubitus values
- Pulmonary stenosis
- Cryptorchidism and delayed puberty
- Lymphoedema
- Mild educational difficulties
- Coagulation defect
What does the impact on growth of skeletal dysplasia depend on?
The part of the skeleton that is affected
What can skeletal dysplasias cause?
Skeletal disproportion
What needs to be done as a result of skeletal dysplasias causing skeletal disproportion?
Measurement and comparison of sitting and standing heights
What is the inheritance patterns of many skeletal dysplasias?
Autosomal dominant
Give 2 examples of skeletal dysplasias
- Achondroplasia
- Hypochondroplasia
What do achondroplasia and hypochondroplasia cause?
Rhizomelic short stature
What is meant by rhizomelic?
Shortening of the proximal limb segment
What is often the genetic cause of achondroplasia/hypochondroplasia?
Mutations of the fibroblast growth factor factor receptor 3 (FGFR3) gene
How do mutations of the FGFR3 gene cause achondroplasia/hypochondroplasia?
The mutatated receptor is constitutionally active and inhibits cartilage formation and thus bone growth
What does spondyloepiphyseal dysplasia lead to?
Markedly impaired trunk growth and less severely affected short limbs
What will be found on examination in spondyloepiphyseal dysplasia?
Disproportionately short sitting height
What treatment may be used in children with short-limbed forms of short stature?
Height may be improved by leg-lengthening surgery
