The CRLF1 gene helps the body send signals that support nerve cells and help control muscle tone, sweating, and body temperature. This gene plays an important role in early growth and in how the body handles stress like feeding or keeping warm. When both copies of the CRLF1 gene do not work properly, it can cause conditions such as Crisponi syndrome or cold induced sweating syndrome, with symptoms that may include feeding trouble in infancy, muscle stiffness or spasms, episodes of fever, and unusual sweating in cool temperatures later on.
What is a gene?
Genes are segments of DNA that give your cells instructions to make molecules or regulate processes in the body. Some genes hold the information needed to produce proteins, the working parts of cells. Others mainly help determine when certain processes happen, where they happen, and how strongly they run. Taken together, genes affect how the body develops and works, and they can influence how you respond to food, stress, or medications. To explore this subject in more detail, you can read more in the LearnHub.
Overview
CRLF1Gene function
What if the gene works
The CRLF1 gene helps make a protein that carries signals between cells, especially in the nervous system. It supports the development and function of nerves involved in body temperature, sweating, and muscle control.
Risk
What if the gene does not work
Different DNA variants in the CRLF1 gene can cause a spectrum from severe newborn Crisponi syndrome to milder cold induced sweating syndrome, with feeding or breathing problems early in life and later unusual sweating, curved spine, and muscle stiffness.
Treatment
What does that mean for your treatment
Pathogenic variants in the CRLF1 gene do not currently have an established CRLF1-specific treatment or drug selection approach; care is supportive and guided by a person’s symptoms.
Conditions associated with CRLF1
Gene function
What if the gene works
Cells use the CRLF1 gene to help pass messages between tissues during growth and everyday upkeep. Its protein is released outside the cell, where it teams up with partner proteins and helps deliver signals to nearby cells. Understanding what the CRLF1 gene does in the body helps explain how cells stay supported over time.
The CRLF1 gene makes a protein that works outside the cell rather than staying inside it. This protein helps cells send and receive signals in a controlled way.
One of its main roles is to help a partner protein called CLCF1 pair up and leave the cell in a stable form. This helps the signal reach other cells effectively.
Once released, the CRLF1 protein and its partner attach to receiver proteins on nearby cells. This switches on internal instructions that support normal cell growth, survival, and development.
What is a variant?
A genetic variant is a slight difference in the DNA sequence within a gene. These differences are common and help shape normal human variation, such as differences in appearance, metabolism, or the way the body responds to environmental influences. Many do not lead to any noticeable effect and are simply part of natural genetic variation. In some situations, though, a variant changes how a gene works more substantially and can contribute to, or cause, a genetic condition.
Genetic variants
What if the gene does not work
Variants in the CRLF1 gene often reduce how much CRLF1 protein is made, how well it folds, or whether it can be released from the cell and pair with proteins for signaling. Milder variants may leave some protein activity, while more disruptive variants that shorten the protein or alter the gene message can reduce or abolish secretion. This spectrum explains how CRLF1 gene variants affect function and in CRLF1 linked conditions can influence when features appear and how they vary.
How variants are linked to conditions
Pathogenic variants in the CRLF1 gene cause cold-induced sweating syndrome type 1, a rare inherited condition. In some babies, the condition first appears as Crisponi syndrome, a more severe early presentation now understood to be part of the same spectrum. This well-established link between CRLF1 gene variants and cold-induced sweating syndrome does not describe a common risk trait. It points to a specific genetic diagnosis.
A variant is not necessarily a diagnosis
Genetic variants are common across the general population and are a normal feature of human biology. Most do not directly affect health and instead reflect natural variation among people. For many genes, having a variant associated with a condition points to a possible link rather than a definite diagnosis, particularly when multiple genes and environmental factors play a role. Still, in some situations, a single well-characterized variant in a specific gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For CRLF1, risk is mainly set by the gene changes a child is born with, not by lifestyle or everyday habits. The chance is higher when both parents carry a harmful CRLF1 change, and it can also be higher in families where the parents are related by blood. There is not enough evidence to say that diet, exercise, or other routine habits change this risk.
Inheritance of CRLF1 variants
CRLF1-related conditions are inherited in an autosomal recessive pattern. In practical terms, CRLF1 inheritance usually means a child needs to receive one altered copy of the CRLF1 gene from each parent to have the condition. Parents who each carry one variant are often healthy themselves, and with each pregnancy there is a 25% chance the child will inherit both variants, a 50% chance the child will be a carrier, and a 25% chance the child will inherit neither variant. This pattern applies to the well-established conditions linked to the CRLF1 gene, including cold induced sweating syndrome type 1 and Crisponi syndrome.
What does my CRLF1 result mean for my family?
For families with a CRLF1-related condition, relatives may also carry the changed gene even if they have no symptoms. Brothers and sisters of an affected child can also be affected or be carriers, and other close relatives may be carriers as well. Family implications are usually strongest when both parents carry a CRLF1 change.
Genetic information
Genetic testing
How you find out about variants
To find CRLF1 variants, doctors use genetic testing for CRLF1 variants, usually with a blood or saliva sample. A lab reads the DNA in the CRLF1 gene and checks for changes linked to the condition in question. Results may show a harmful variant, a harmless variant, or a change with unclear meaning.
When should I consider getting a genetic test?
Testing for CRLF1 may be considered if a baby or child has signs of this rare inherited condition, such as severe feeding problems, muscle stiffness, unexplained high fever in infancy, or sweating brought on by cold. It can also help when there is a family history or after an affected child, to show whether relatives carry the changed gene.
A genetic result is only one part of your health story
Genetic results can provide useful insight, but how much they reveal depends on the condition and on the type of variant involved. Over time, lifestyle, environment, age, and medical history all help shape how the body functions. For some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is best understood alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas like medication response, these results can also help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Two people can take the same treatment, yet one may get the intended benefit while the other may notice less effect or be more sensitive to side effects. This happens in part because inherited differences can change how the body breaks down, moves, or responds to a drug, and these differences are a common part of normal human biology.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in a person’s genes can affect the way they respond to medications. It studies gene-drug patterns to help explain why the same treatment may work differently in different people. For many drugs, genes influence both how strong a medicine’s effect is and how the body processes it. This information can support more informed, more individualized treatment choices. More detail on this topic is available in the LearnHub.
Drugs influenced by the CRLF1 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication response, so questions about symptoms, treatment, or side effects are best discussed with your doctor.
History
The CRLF1 gene entered the medical literature in the late 1990s, when researchers identified it as part of a newly recognized family of signaling-related genes. Soon afterward, studies of families with an inherited condition later understood as Crisponi syndrome linked harmful variants in the CRLF1 gene to the condition. From these first observations, research expanded steadily. Doctors then recognized that cold-induced sweating syndrome could result from variants in the same gene, helping unite what had seemed like separate conditions into one clinical spectrum. Over time, descriptions became more precise, and the history of the CRLF1 gene became closely tied to improved diagnosis for affected families.