CNTNAP1
CNTNAP1-related neuropathy is a rare and severe form that begins before or at birth. It affects a protein that organizes the connection points along a nerve, and it usually causes profound weakness in newborns. This is one of the most serious conditions in the CMT family.
What CNTNAP1 is
CNTNAP1-related neuropathy is caused by changes in the CNTNAP1 gene, which makes a protein called CASPR1. CASPR1 helps build the precise junctions along a nerve fiber where the insulation meets the nerve, the points that make fast, reliable nerve signals possible.
When CASPR1 is missing or does not work, those junctions do not form properly, and nerve signals are severely disrupted from the very beginning of life. This is why CNTNAP1 usually appears before birth or in the newborn period, rather than later like most forms of CMT.
It is important to be clear that this is a severe condition. Many babies have signs before birth, such as extra amniotic fluid and reduced movement, and are born with profound low muscle tone, breathing difficulty, and joint stiffness. The outlook is serious, and care centers on comfort, breathing, feeding, and support for the whole family.
How common it is. CNTNAP1-related neuropathy is very rare, with a few dozen affected children described in the medical literature to date.
Common signs and symptoms
Reported symptoms and their severity vary from person to person, even within the same family. This is a general picture, not a prediction for any one person.
- Signs before birth in some pregnancies, such as excess amniotic fluid (polyhydramnios) and reduced fetal movement
- Profound low muscle tone (hypotonia) and weakness at birth
- Breathing difficulty, often needing support
- Feeding and swallowing difficulty
- Joint stiffness or contractures (sometimes called arthrogryposis)
Onset and how it changes over time
CNTNAP1-related neuropathy is present from birth and is severe. Many affected infants need breathing and feeding support from the start, and for some the condition is life-limiting in early life. A number of children do survive beyond infancy, with significant, ongoing medical needs.
Because the condition is so serious and begins so early, care focuses on the whole family: expert support for breathing, feeding, and comfort, honest guidance from an experienced team, and connection to others who understand. Every child is different, and those conversations are best had with a specialist team who knows your situation.
How it is inherited
CNTNAP1-related neuropathy is inherited in an autosomal recessive pattern: it takes two changed copies of the gene, one from each parent, who are usually unaffected carriers. When both parents carry a change, each pregnancy has about a 1 in 4 (25 percent) chance of being affected. For families who have had an affected child, a genetic counselor can explain testing and options for future pregnancies.
Autosomal recessive inheritance
It takes two changed copies, one from each parent, to cause CMT. When both parents are unaffected carriers, each child has about a 1 in 4 chance of being affected and a 1 in 2 chance of being a carrier.
- Affected
- Carrier
- Unaffected
- Male
- Female
This diagram shows a typical family. Real families vary, and it does not predict any specific outcome. A genetic counselor can walk through what it means for yours.
Faces of CMT
Real families living with CNTNAP1, in their own words.
James · James' Cure
Born with an ultra-rare CNTNAP1 mutation, James and his family are pushing for a gene therapy.
Read their story ›Frequently asked questions
What is CNTNAP1-related neuropathy?
CNTNAP1-related neuropathy is a rare and severe form of CMT caused by changes in the CNTNAP1 gene, which makes a protein called CASPR1. CASPR1 helps build the precise junctions along a nerve fiber where the insulation meets the nerve, the points that make fast, reliable nerve signals possible. When CASPR1 is missing or does not work, those junctions do not form properly, and nerve signals are severely disrupted from the very beginning of life. Genetic testing confirms the diagnosis.
What gene causes CNTNAP1-related neuropathy?
It is caused by changes in the CNTNAP1 gene, which makes a protein called CASPR1 (contactin-associated protein 1). This protein organizes the junctions along a nerve fiber where the insulation meets the nerve. When it is missing or does not work, nerve signals are severely disrupted, which is why the condition usually appears before birth or in the newborn period rather than later like most forms of CMT.
What are the symptoms of CNTNAP1-related neuropathy?
Some pregnancies show signs before birth, such as excess amniotic fluid (polyhydramnios) and reduced fetal movement. Babies are typically born with profound low muscle tone (hypotonia) and weakness, breathing difficulty that often needs support, and feeding and swallowing difficulty. Joint stiffness or contractures, sometimes called arthrogryposis, may also be present. This is a severe condition, and care centers on comfort, breathing, feeding, and support for the whole family.
How is CNTNAP1-related neuropathy inherited?
CNTNAP1-related neuropathy is inherited in an autosomal recessive pattern: it takes two changed copies of the gene, one from each parent, who are usually unaffected carriers. When both parents carry a change, each pregnancy has about a 1 in 4 (25 percent) chance of being affected. For families who have had an affected child, a genetic counselor can explain testing and options for future pregnancies.
How serious is CNTNAP1-related neuropathy?
CNTNAP1-related neuropathy is present from birth and is severe. Many affected infants need breathing and feeding support from the start, and for some the condition is life-limiting in early life. A number of children do survive beyond infancy, with significant, ongoing medical needs. Every child is different, and those conversations are best had with a specialist team who knows your situation.
Confirm your subtype
If you have a clinical CMT diagnosis but no confirmed gene, genetic testing is how you learn your subtype. CMT Genie helps you and your provider get tested and connects you with telehealth genetic counseling.
Clinical information on this page is based on peer-reviewed literature (CNTNAP1 congenital neuropathy cohorts) and OMIM 616286 / 618186. Verified 2026-07-08.