Snyder-Robinson syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Snyder-Robinson syndrome is a condition characterized by intellectual disability, muscle and bone abnormalities, and other problems with development. It occurs exclusively in males.

Males with Snyder-Robinson syndrome have delayed development and intellectual disability beginning in early childhood. The intellectual disability can range from mild to profound. Speech often develops late, and speech difficulties are common. Some affected individuals never develop any speech.

Most affected males are thin and have low muscle mass, a body type described as an asthenic habitus. Weakness or "floppiness" (hypotonia) typically becomes apparent in infancy, and the loss of muscle tissue continues with age. People with this condition often have difficulty walking; most have an unsteady gait.

Snyder-Robinson syndrome causes skeletal problems, particularly thinning of the bones (osteoporosis) that starts in early childhood. Osteoporosis causes the bones to be brittle and to break easily, often during normal activities. In people with Snyder-Robinson syndrome, broken bones occur most often in the arms and legs. Most affected individuals also develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Affected individuals tend to be shorter than their peers and others in their family.

Snyder-Robinson syndrome is associated with distinctive facial features, including a prominent lower lip; a high, narrow roof of the mouth or an opening in the roof of the mouth (a cleft palate); and differences in the size and shape of the right and left sides of the face (facial asymmetry). Other signs and symptoms that have been reported include seizures that begin in childhood and abnormalities of the genitalia and kidneys.

ORPHANET DEFINITION X-linked intellectual disability, Snyder type is a rare X-linked intellectual disability syndrome characterized by hypotonia, asthenic build with diminished muscle mass, severe generalized psychomotor delay, unsteady gait and moderate to severe intellectual disability, as well as a long, thin, asymmetrical face with prominent lower lip, long fingers and toes and nasal, dysarthric or absent speech. Bone abnormalities (e.g., osteoporosis, kyphoscoliosis, fractures, joint contractures) are also characteristic. Myoclonic, or myoclonic-like, seizures and renal abnormalities have been associated in some patients.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

X-linked recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 21.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; 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.

Kyphoscoliosis · Very frequent (99-80%)

An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.

Arachnodactyly · Frequent (79-30%)

Abnormally long and slender fingers (spider fingers).

Cleft palate · Frequent (79-30%)

Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Disproportionate tall stature · Frequent (79-30%)

A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim.

Facial asymmetry · Frequent (79-30%)

An abnormal difference between the left and right sides of the face.

Floppy infant · Frequent (79-30%)

Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape).

Hypernasal speech · Frequent (79-30%)

A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.

Kyphosis · Frequent (79-30%)

Exaggerated anterior convexity of the thoracic vertebral column.

Long face · Frequent (79-30%)

Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).

Long toe · Frequent (79-30%)

Toes that appear disproportionately long compared to the foot.

Narrow face · Frequent (79-30%)

Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).

Osteoporosis · Frequent (79-30%)

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).

Slender toe · Frequent (79-30%)

Toes that are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual.

Thick lower lip vermilion · Frequent (79-30%)

Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).

Other findings in the same source

From: Orphanet

Additional reported features include Decreased muscle mass (Frequent (79-30%)); Unsteady gait (Frequent (79-30%)); Abnormal facial shape (Occasional (29-5%)); Absent speech (Occasional (29-5%)); Anteverted nares (Occasional (29-5%)); Asymmetry of the ears (Occasional (29-5%)); Bulbous nose (Occasional (29-5%)); Cryptorchidism (Occasional (29-5%)); Delayed speech and language development (Occasional (29-5%)); Dental crowding (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Adolescent; Childhood; Infancy

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

X-linked recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 21.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An X-linked recessive pattern involves a gene on the X chromosome. The number of X chromosomes and the particular genetic change influence how a condition is expressed. A genetic counsellor should interpret the result and the family history before discussing risks for relatives or future pregnancies.

Which doctor should you see?

The suggested department for discussing Snyder-Robinson 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 Snyder-Robinson 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.