Russell-Silver Syndrome - A Rare Congenital Growth Disorder

Introduction

Russell-Silver syndrome is a developmental disorder that causes slow growth before and after birth. Babies with this condition are born with low birth weight and frequently fail to grow and gain weight at the anticipated rate. Dr. Silver and Dr. Russell described Russell-Silver syndrome in 1953 and 1954, respectively. Initially, it was believed that they were two distinct disorders; it took nearly 20 years for the doctors to recognize that they were seeing different aspects of the same condition. In the United States, the disorder is known as Russell-Silver syndrome, and in Europe, it is known as Silver-Russell syndrome.

What Is Russell-Silver Syndrome?

Russell-Silver syndrome (RSS) is a rare genetic growth disorder characterized by intrauterine growth restriction, poor postnatal growth, prominent forehead, large head size, triangular facial appearance, body asymmetry, and feeding difficulties.

Russell-Silver syndrome has complex genetic causes linked to specific genes controlling growth. Sometimes the genetic cause is unknown. The Russell-Silver syndrome affects about one in every 50,000 to 100,000 births. However, the exact incidence of Russell-Silver syndrome is not yet identified. RSS affects males and females equally.

What Are the Causes of Russell-Silver Syndrome?

Russell-Silver syndrome has been associated with several genetic causes. The disorder is frequently caused by improper regulation of specific genes that usually control growth. In approximately 60 % of people with Russell-Silver syndrome, genetic changes in chromosomes 7 or 11 have been linked to the condition. However, no genetic cause has been identified in approximately 40 % of people diagnosed with RSS. Changes in chromosomes other than 7 and 11 can also be responsible for the condition.

Researchers believe that methylation alterations on the short (p) arm of chromosome 11 at location 15 (11p15) are responsible for 30 to 50 % of all cases of Russell-Silver syndrome. Methylation is a chemical reaction in which small molecules known as methyl groups are attached to specific segments of DNA.

Russell-Silver syndrome has also been associated with other genetic causes, including duplications, deletions, and chromosomal abnormalities. However, the genetic changes that could cause RSS are still being investigated by researchers.

What Are the Symptoms Associated With Russell-Silver Syndrome?

Symptoms associated with Russell-Silver syndrome vary significantly between children. The condition can have a wide range of effects on the child's body.

The following are some of the common symptoms of Russell-Silver syndrome:

• Fetal growth restriction or intrauterine growth restriction.

• Short stature.

• Low birth weight.

• Feeding problems.

• Low muscle tone.

• Hypoglycemia.

• Excessive sweating.

• Body asymmetry.

• Failure to thrive.

• Narrow chin.

• Large head size.

• Protruding forehead.

• Delayed closure of fontanelle.

• Triangular-shaped face.

• Dental crowding.

• Hypodontia.

• Small teeth.

• Scoliosis.

• Cleft palate.

• Postnatal growth retardation.

• Abnormal male genitalia.

• Decreased testicular size.

• Delayed skeletal maturation.

• Upper limb asymmetry.

• Cardiovascular abnormalities.

• Secondary microcephaly.

How Is Russell-Silver Syndrome (RSS) Diagnosed?

Russell-Silver syndrome is challenging to diagnose because the symptoms and severity of the condition vary greatly. RSS symptoms are most noticeable in infancy and early childhood. It makes diagnosis more difficult in older children. Russell-Silver syndrome is a genetically diverse condition. In approximately 60 % of cases, genetic testing confirms the clinical diagnosis.

Russell-Silver syndrome was diagnosed based on clinical symptoms for many years. Unfortunately, this resulted in overlapping disorders with comparable clinical symptoms, such as 12q14 microdeletion syndrome and Temple syndrome.

An international consensus describing the procedures doctors should follow to diagnose Silver-Russell syndrome was released in 2017.

It is now advised to check for mUPD7 (maternal uniparental disomy of chromosome 7) and 11p15 loss of methylation first.

If negative, the affected person should undergo testing for mUPD16 (maternal uniparental disomy of chromosome 16) and mUPD20 (maternal uniparental disomy of chromosome 20).

What Are the Treatment Options for Russell-Silver Syndrome?

Multidisciplinary follow-up and early, targeted intervention is required to manage RSS. As RSS is present from birth, the first few years of life are crucial for a child's growth. The treatment of RSS focuses on managing the symptoms to help the child develop as normally as possible. The treatment for RSS is determined based on the severity of the condition. Management of RSS should begin as soon as possible for the best possible outcome for the child.

• Growth Hormone (GH) Therapy - GH therapy is frequently used to treat RSS. Hormones are typically administered by injection daily from age two through adolescence. Growth hormone therapy may be effective even if the patient does not have a deficiency of growth hormones and has been shown to accelerate patient growth.

• Feeding Issues - Acid reflux associated with RSS can be treated with postural changes and medications. Medications like proton pump inhibitors and H2 blockers can be used to heal damaged gastric tissues. Nutritional and caloric supplements, therapy for feeding aversion and oral motor issues, enteral tube feeding, and appetite stimulation are the other methods used for treating feeding issues.

• Genetic Counseling - RSS is a genetic disorder rarely passed down to children. Individuals suffering from this condition should consult a genetic counselor. A genetic counselor can explain the chances of the child developing RSS.

What Are the Other Syndromes That May Be Mistakenly Diagnosed as Russell-Silver Syndrome?

• Bloom Syndrome - It is a genetic disorder that causes short stature and an increased risk of cancers.

• Fanconi Anemia Syndrome - This syndrome is characterized by a genetic error in DNA repair that may result in cancer.

• Nijmegen Breakage Syndrome - It is a hereditary condition that results in distinct facial characteristics, a small head, short stature, etc.

What Are the Complications Associated With Russell-Silver Syndrome?

The child may face health issues due to the physical impacts of Russell-Silver syndrome. These difficulties may include:

• Developmental delay.

• Acid reflux.

• Speech delay.

• Growth delay.

• Walking difficulties.

• Learning difficulties.

• Poor appetite.

• Gastric issues.

• Kidney problems.

• Urinary issues.

• Reproductive issues.

In addition, studies have suggested that adults with Russell-Silver syndrome could develop new health issues as they age. These complications include:

• Reduced bone density.

• Low sex drive.

• Low muscle mass.

• Metabolic syndrome.

• Testicular cancer.

• Dystonia.

Conclusion

Russell-Silver syndrome (RSS), or Silver-Russell syndrome (SRS), is a congenital disorder. This syndrome is characterized by reduced growth and limb or facial asymmetry.

Low birth weight, distinctive facial features, large head, feeding difficulties, poor appetite, learning disabilities, digestive system problems, and short stature are the common symptoms of RSS. Managing children with RSS should begin as soon as possible and frequently necessitates the involvement of multiple health professionals.