IllnessSilver-Russell syndrome, differential diagnosis

Step 1: MS-MLPA chromosome 11

Step 2: MS-MLPA UPD7 > eventually also parental DNA anased after index case

Step 3: NGS +

Silver-Russell syndrome (SRS) is characterized by slow growth before and after birth. The infants are small and do not thrive, while on the other hand the head size is appropriate for the age. Affected infants suffer from hypoglycemia due to feeding problems. Adults with SRS have also short statures, men averaging ~150 cm and women ~140 cm. Many children with SRS have a small, triangular face with prominent forehead, narrow chin, small jaw and down-turned corners of the mouth. In addition, clinodactyly, asymmetrical or uneven growth of some body parts are observed as well as digestive system abnormalities. SRS is also associated with an increased risk of developmental delays, speech and learning problems. The genetic causes of SRS are complex and are often due to abnormal gene regulation concerning chromosomes 7 and 11. Some 30-50% of SRS cases are due to changes in methylation on chromosome 11p in the H19 and IGF2 genes. Gene alterations on chromosome 7 can cause SRS by, for example, uniparental disomy (7-10% of cases). In ~40%, the cause of SRS remains unexplained. Negative molecular genetic test results do not, therefore, exclude the clinical diagnosis of SRS. Most cases of SRS occur sporadically; only in rare cases the disease appears to be inherited in an autosomal dominant or autosomal recessive manner.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1324/

• Alias: Russel-Silver syndrome
• Alias: Silver-Russell dwarfism
• Allelic: Adenomas, salivary gland pleomorphic, somatic (PLAG1)
• Allelic: Aplastic anemia (NBN)
• Allelic: Beckwith-Wiedemann syndrome (CDKN1C)
• Allelic: Leukemia, acute lymphoblastic (NBN)
• 3-M syndrome 1 (CUL7)
• 3-M syndrome 2 (OBSL1)
• 3-M syndrome 3 (CCDC8)
• Bloom syndrome (BLM)
• Fanconi anemia (BRCA2, BRIP1, ERCC4, MAD2L2, PALB2, RAD51, RAD51C, RFWD3, SLX4, UBE2T, XRCC2)
• Fanconi anemia (FANCA-FANCL/FANCW)
• Growth retardation with deafness + mental retardation due to IGF1 deficiency (IGF1)
• IMAGE syndrome (CDKN1C)
• Insulin-like growth factor I, resistance to (IGF1R)
• Meier-Gorlin syndrome 1 (ORC)
• Meier-Gorlin syndrome 2 (ORC4)
• Meier-Gorlin syndrome 3 (ORC6)
• Meier-Gorlin syndrome 4 (CDT1)
• Meier-Gorlin syndrome 5 (CDC6)
• Meier-Gorlin syndrome 6 (GMNN)
• Meier-Gorlin syndrome 7 (CDC45)
• Meier-Gorlin syndrome 8 (MCM5)
• Nijmegen breakage syndrome (NBN)
• Silver-Russell syndrome 1 (ICR1)
• Silver-Russell syndrome 2 (uniparental disomy, maternal)
• Silver-Russell syndrome 3 (IGF2)
• Silver-Russell syndrome 4 (PLAG1)
• Silver-Russell syndrome 5 (HMGA2)
• Warsaw breakage syndrome (DDX11)