Coffin-Lowry syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Coffin-Lowry syndrome is a condition that affects many parts of the body. The signs and symptoms are usually more severe in males than in females, although the features of this disorder range from very mild to severe in affected women.

Males with Coffin-Lowry syndrome typically have severe to profound intellectual disability and delayed development. Affected women may be cognitively normal, or they may have intellectual disability ranging from mild to profound. Beginning in childhood or adolescence, some people with this condition experience brief episodes of collapse when excited or startled by a loud noise. These attacks are called stimulus-induced drop episodes (SIDEs).

Most affected males and some affected females have distinctive facial features including a prominent forehead, widely spaced and downward-slanting eyes, a short nose with a wide tip, and a wide mouth with full lips. These features become more pronounced with age. Soft hands with short, tapered fingers are also characteristic of Coffin-Lowry syndrome. Additional features of this condition include short stature, an unusually small head (microcephaly), progressive abnormal curvature of the spine (kyphoscoliosis), and other skeletal abnormalities.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the RPS6KA3 gene cause Coffin-Lowry syndrome. This gene provides instructions for making a protein that is involved in signaling within cells. Researchers believe that this protein helps control the activity of other genes and plays an important role in the brain. The protein is involved in cell signaling pathways that are required for learning, the formation of long-term memories, and the survival of nerve cells. Gene mutations result in the production of little or no RPS6KA3 protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin-Lowry syndrome.

Some people with the features of Coffin-Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause of the condition is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, males (who have one X chromosome in each cell) experience more severe signs and symptoms of the disorder than females (who have two X chromosomes in each cell). A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Between 70 percent and 80 percent of people with Coffin-Lowry syndrome have no history of the condition in their families. These cases are caused by new mutations in the RPS6KA3 gene. The remaining 20 percent to 30 percent of affected individuals have other family members with Coffin-Lowry syndrome.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of this condition is uncertain, but researchers estimate that the disorder affects 1 in 40,000 to 50,000 people.

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.

Abnormal dental morphology · Very frequent (99-80%)

An abnormality of the morphology of the tooth.

Abnormal diaphysis morphology · Very frequent (99-80%)

An abnormality of the structure or form of the diaphysis, i.e., of the main or mid-section (shaft) of a long bone.

Abnormal form of the vertebral bodies · Very frequent (99-80%)

Abnormal form of vertebral body, which is the central cylindrical portion of the vertebra that together with other structures such as the vertebral arch, pedicles, laminae, spinous process, transverse processes, and articular facets makes up a vertebra.

Abnormality of speech or vocalization · Very frequent (99-80%)

An abnormality in the sound (volume) or cadence (rate) of speech.

Anteverted nares · Very frequent (99-80%)

Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).

Broad finger · Very frequent (99-80%)

Increased width of a non-thumb digit of the hand.

Coarse facial features · Very frequent (99-80%)

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Craniofacial hyperostosis · Very frequent (99-80%)

Excessive growth of the craniofacial bones.

Other findings in the same source

From: Orphanet

Additional reported features include Delayed skeletal maturation (Very frequent (99-80%)); Depressed nasal bridge (Very frequent (99-80%)); Downslanted palpebral fissures (Very frequent (99-80%)); Epicanthus (Very frequent (99-80%)); Everted lower lip vermilion (Very frequent (99-80%)); Frontal bossing (Very frequent (99-80%)); Hypertelorism (Very frequent (99-80%)); Hypodontia (Very frequent (99-80%)); Hypotonia (Very frequent (99-80%)); Intellectual disability (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Coffin-Lowry 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 Coffin-Lowry 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.