Silver-Russell syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Silver-Russell syndrome is a rare disorder that is characterized by slow growth before and after birth. Babies with this condition typically have a low birth weight and often do not grow and gain weight at the expected rate (failure to thrive). Head growth is normal, however, so the head may appear large compared to the rest of the body. In some affected individuals, one side of the body may be bigger than the other.

Affected children often have difficulty feeding. Some children develop recurrent episodes of low blood glucose (hypoglycemia). Gastrointestinal problems, such as vomiting and a backflow of stomach acid into the esophagus (called gastroesophageal reflux or GERD), are also common.

Adults with Silver-Russell syndrome are typically shorter than average and may have an increased risk of developing metabolic problems such as type 2 diabetes (the most common form of diabetes). Affected individuals often have asymmetric or uneven growth of certain parts of the body, such as the arms and legs. Additional skeletal features may include an unusual curving of the fifth finger (clinodactyly), short fingers (brachydactyly), and abnormal curvature of the spine (scoliosis).

Many people with Silver-Russell syndrome have a small, triangular face with distinctive features, including a prominent forehead, a narrow chin, a small jaw, and downturned corners of the mouth.

Other features can include the delayed development of motor skills, speech and language problems, and learning disabilities.

ORPHANET DEFINITION A rare imprinting disorder, characterized by fetal growth restriction with no catch-up associated with feeding anomalies and dysmorphic features.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant+New variant

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Annual incidence: 1-5 / 10 000; Europe; Value and class. Point prevalence: 1-9 / 100 000; United Kingdom; Value and class. Prevalence at birth: 1-9 / 1 000 000; Europe; Value and class. Point prevalence: 1-9 / 1 000 000; Europe; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Blue sclerae · Very frequent (99-80%)

An abnormal bluish coloration of the sclera.

Cachexia · Very frequent (99-80%)

Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease.

Feeding difficulties · Very frequent (99-80%)

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Intrauterine growth retardation · Very frequent (99-80%)

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Low-set ears · Very frequent (99-80%)

Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.

Postnatal growth retardation · Very frequent (99-80%)

Slow or limited growth after birth.

Prominent forehead · Very frequent (99-80%)

Forward prominence of the entire forehead, due to protrusion of the frontal bone.

Relative macrocephaly · Very frequent (99-80%)

A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.

Short stature · Very frequent (99-80%)

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Triangular face · Very frequent (99-80%)

Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.

Abnormal appendicular skeleton morphology · Frequent (79-30%)

An abnormality of the appendicular skeletal system, consisting of the of the limbs, shoulder and pelvic girdles.

Abnormality of male external genitalia · Frequent (79-30%)

Any structural abnormality of male external genitalia.

Abnormality of the calcaneus · Frequent (79-30%)

An abnormality of the calcaneus, also known as the heel bone, one of the or heel bone, one of the components of the tarsus of the foot which make up the heel.

Abnormally high-pitched voice · Frequent (79-30%)

A persistent (minutes to hours) abnormal increase in the pitch (frequency) of the voice for the context or social situation or significantly different from baseline of the individual.

Other findings in the same source

From: Orphanet

Additional reported features include Arthralgia (Frequent (79-30%)); Asymmetric growth (Frequent (79-30%)); Clinodactyly of the 5th finger (Frequent (79-30%)); Constipation (Frequent (79-30%)); Cryptorchidism (Frequent (79-30%)); Decreased testicular size (Frequent (79-30%)); Delayed cranial suture closure (Frequent (79-30%)); Delayed skeletal maturation (Frequent (79-30%)); Dental crowding (Frequent (79-30%)); Downturned corners of mouth (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Antenatal; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant+New variant

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Annual incidence: 1-5 / 10 000; Europe; Value and class. Point prevalence: 1-9 / 100 000; United Kingdom; Value and class. Prevalence at birth: 1-9 / 1 000 000; Europe; Value and class. Point prevalence: 1-9 / 1 000 000; Europe; Class only.

Which doctor should you see?

The suggested department for discussing Silver-Russell syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Silver-Russell syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.