Russell-Silver syndrome

• IUGR may occur in a number of congenital disorders, including Mulibrey nanism and many chromosome disorders.^[2] Chromosome abnormalities to consider in the differential diagnosis of RSS include:^[1][2]
  • mosaic Turner syndrome
  •  diploid/triploid mixoploidy (because of limb asymmetry)
  • Yq deletions
  • other chromosome deletions (involving 12p14 , 15q26.3, and a distal deletion of 22q11.2)
  • rearrangements of chromosome 17q25
• Three M syndrome is an extremely rare genetic disorder with features that include low birth weight, short stature, characteristic head and facial features, and distinctive bone abnormalities.^[1]
• Disorders of DNA repair (chromosome breakage disorders), including Fanconi anemia, Bloom syndrome, and Nijmegen breakage syndrome, are often associated with IUGR and short stature. In these conditions, additional features such as small head size (microcephaly), limb abnormalities, and abnormal sensitivity to sunlight (photosensitivity), are often evident.^[1][2]
• Fetal alcohol spectrum disorders (FASDs) may be characterized by mental and physical birth defects from maternal use of alcohol during pregnancy. The range and severity of symptoms vary greatly. In some cases, learning delays or intellectual disability occurs without any obvious physical abnormalities.^[1]
• IMAGe syndrome is characterized by IUGR, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital abnormalities. A skeletal survey should be performed to exclude a skeletal dysplasia that may mimic RSS.^[2]
• One condition that has been confused with RSS is an X-linked disorder of short stature with skin hyperpigmentation. It has sometimes been referred to as X-linked RSS. This condition may be difficult to distinguish from classic RSS in the absence of a positive family history.^[2]

The presence of other particular features (especially those atypical for RSS) should prompt consideration of a diagnosis other than RSS. Atypical features may include microcephaly; notable global developmental delay or intellectual disability (without a related explanation); absence of severe feeding difficulties; the presence of additional congenital anomalies; and facial dysmorphism. Disproportionate short stature is suggestive of skeletal dysplasia, and photosensitivity or recurrent respiratory infections may be suggestive of chromosome breakage disorders. Because RSS is generally sporadic (not inherited), a family history of growth failure and/or consanguinity might suggest a different diagnosis.^[3]

People with a questions about a possible genetic diagnosis are encouraged to meet with a genetics professional who can provide detailed information and support.

• karyotype and chromosomal microarrays to exclude other disorders
• evaluation of patient and parental blood for uniparental disomy of chromosome 7 and hypomethylation (a form of DNA modification) at chromosome 11p15 by polymerase chain reaction (PCR)
• hand x-ray to determine bone age - findings may include:
  • delayed bone age
  • white or ivory appearance on parts of the fingers (ivory epiphyses of distal phalanges)
  • short middle bone of the pinky (small middle phalanx of the fifth finger), which occurs in 80% of people with RSS
  • extra bone formation at the base of the pointer finger (pseudoepiphyses at base of second metacarpal)^[4]