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PubMed This is a summary of 8 peer-reviewed journal articles Updated
Medical Genetics · Deafness-Dystonia-Cerebral Hypomyelination Syndrome

Recognizing the Symptoms of BCAP31-Related Syndrome

At a Glance

BCAP31-related syndrome often begins in infancy with low muscle tone, feeding and growth problems, hearing loss, developmental delay, and later movement changes. Symptoms vary widely, so each child needs individualized hearing, movement, swallowing, and liver checks.

While every child with BCAP31-related syndrome (DDCH) follows their own path, the condition typically presents with a specific group of symptoms that emerge early in life. Because this is a genetic condition on the X chromosome, the way these symptoms appear can vary significantly between boys and girls, and even between children with different types of genetic variants [1][2].

Early Warning Signs and Growth

In many cases, the first signs of DDCH appear within the first three months of life [3]. Parents often notice:

  • Hypotonia: Often described as “floppiness,” this is a state of low muscle tone where a baby may feel limp when held [3][2].
  • Failure to Thrive: This is a medical term for when a baby has difficulty gaining weight or growing at the expected rate [3][2].
  • Microcephaly: Some children are born with or develop a smaller-than-average head size, which can be a sign of how the brain is developing [3].
  • Feeding Challenges: Difficulty sucking or swallowing is common in infancy. Be vigilant for signs of aspiration, such as coughing or choking with feeds, a wet or gurgly voice, color change, or prolonged meals, which warrant a swallowing assessment [4].

The Movement Spectrum: From Floppy to Stiff

One of the most complex parts of DDCH is how it affects movement. It is not uncommon for a child to start with low muscle tone (hypotonia) and then develop different types of involuntary movements as they grow [3][5].

  • Dystonia: This is characterized by muscles contracting involuntarily, which can cause twisting or repetitive movements [1][3].
  • Choreoathetosis: These are involuntary, “dance-like” or writhing movements that can affect the hands, feet, and face [1][3].
  • Seizures: While not every child will have them, seizures are a reported part of the syndrome and may require medication to manage [2][6].

Hearing and the Brain

The “Deafness” in DDCH is typically sensorineural hearing loss, meaning it stems from the inner ear or the nerve pathways [1][3]. This hearing loss is often present from birth (congenital) and is generally considered non-progressive, meaning it does not typically get worse over time [7][8].

On a brain MRI, doctors look for cerebral hypomyelination—a lack of the fatty “insulation” (myelin) that helps nerves send signals [1]. This lack of insulation, along with a thinning of the corpus callosum (the bridge between the two sides of the brain), is why children experience severe developmental delays and intellectual disabilities [1][2].

The Role of the Liver

A frequently overlooked symptom is the elevation of transaminases, specifically liver enzymes AST and ALT [1].

  • The Pattern: For most children, these elevations are asymptomatic. However, AST and ALT indicate possible cell injury, not a complete measure of liver function [6].
  • Monitoring: While often transient, cholestasis or impaired synthetic function may require further assessment of bilirubin, GGT, albumin, and clotting factors [1][6]. Seek prompt medical attention for jaundice, dark urine, pale stools, unusual bleeding, marked sleepiness, or persistent vomiting.

Why Symptoms Vary: Sex and Variant Type

Because the BCAP31 gene is on the X chromosome, the “dose” of the working gene matters.

  • In Males: Boys have only one X chromosome. While loss-of-function variants are broadly associated with more severe symptoms, and missense variants are sometimes reported with a milder or later-onset phenotype [1][7], variant class alone cannot reliably predict an individual child’s course. Some missense variants can be severe.
  • In Females: Girls have two X chromosomes. Most female carriers are asymptomatic (have no symptoms) because their “healthy” X chromosome compensates for the “affected” one [1]. However, expression varies with X-inactivation and the specific variant. Some females experience learning difficulties, intellectual disabilities, or hearing loss [1][3]. In very rare cases, a girl can be as severely affected as a boy [6].

Understanding these variations helps explain why your child’s experience might be different from another child with the same diagnosis.

Common questions in this guide

What are the first signs of BCAP31-related syndrome in a baby?
Early signs often appear in the first three months and can include low muscle tone or floppiness, feeding difficulty, poor weight gain, a small head size, or reduced response to sound. Developmental delays may become clearer as the child grows.
What movement problems can children with BCAP31-related syndrome develop?
A child may start with low muscle tone and later develop dystonia, which causes involuntary twisting or tightening, or choreoathetosis, which causes dance-like or writhing movements. Seizures can also occur, although not every child has them.
What type of hearing loss is associated with BCAP31-related syndrome?
The hearing loss is usually present from birth and involves the inner ear or hearing nerve pathways, a pattern called sensorineural hearing loss. It is generally non-progressive, but formal hearing evaluation is important and may include testing for problems with nerve signal transmission.
Why does my child need liver enzyme tests?
AST and ALT may be elevated, often without symptoms, and indicate possible cell injury rather than providing a complete measure of liver function. The medical team may also check bilirubin, GGT, albumin, and clotting factors, especially if jaundice, dark urine, pale stools, unusual bleeding, marked sleepiness, or persistent vomiting occurs.
How can BCAP31-related syndrome differ between boys and girls?
Symptoms can differ because boys have one X chromosome and are often more severely affected, while most female carriers have no symptoms. Some females have learning difficulties, intellectual disability, or hearing loss, and X-inactivation and the specific BCAP31 variant can change the pattern.
Can the type of BCAP31 variant predict how severe my child’s symptoms will be?
Loss-of-function variants are broadly associated with more severe symptoms, while some missense variants have been associated with milder or later-onset features. However, variant class cannot reliably predict an individual child’s course, and some missense variants can also cause severe disease.
What might a brain MRI show in BCAP31-related syndrome?
A brain MRI may show cerebral hypomyelination, meaning less of the insulating myelin around nerve pathways, along with a thin corpus callosum, the bridge between the brain’s two sides. These findings may help explain developmental and movement problems.

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References

References (8)
  1. 1

    Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants.

    Whalen S, Shaw M, Mignot C, et al.

    European journal of human genetics : EJHG 2021; (29(9)):1405-1417 doi:10.1038/s41431-021-00821-0.

    PMID: 33603160
  2. 2

    Case Report: The first Korean familial case of BCAP31-related deafness, dystonia, and cerebral hypomyelination.

    Suh YA, Hwang J, Seo GH, et al.

    Frontiers in pediatrics 2024; (12()):1488095 doi:10.3389/fped.2024.1488095.

    PMID: 39911770
  3. 3

    BCAP31-associated encephalopathy and complex movement disorder mimicking mitochondrial encephalopathy.

    Albanyan S, Al Teneiji A, Monfared N, Mercimek-Mahmutoglu S

    American journal of medical genetics. Part A 2017; (173(6)):1640-1643 doi:10.1002/ajmg.a.38127.

    PMID: 28332767
  4. 4

    Whole exome sequencing reveals a dual diagnosis of BCAP31-related syndrome and glutaric aciduria III.

    Huggins E, Jackson DG, Young SP, Kishnani PS

    Molecular genetics and metabolism reports 2024; (40()):101117 doi:10.1016/j.ymgmr.2024.101117.

    PMID: 39101156
  5. 5

    BCAP31-related syndrome: The first de novo report.

    Rinaldi B, Van Hoof E, Corveleyn A, et al.

    European journal of medical genetics 2020; (63(2)):103732 doi:10.1016/j.ejmg.2019.103732.

    PMID: 31330203
  6. 6

    De novo mutation and skewed X-inactivation in girl with BCAP31-related syndrome.

    Kao HJ, Chiang HL, Chen HH, et al.

    Human mutation 2020; (41(10)):1775-1782 doi:10.1002/humu.24080.

    PMID: 32652807
  7. 7

    An X-Linked Ataxia Syndrome in a Family with Hearing Loss Associated with a Novel Variant in the BCAP31 Gene.

    Paucar M, Li T, Bergendal Å, et al.

    Movement disorders : official journal of the Movement Disorder Society 2025; (40(4)):672-682 doi:10.1002/mds.30116.

    PMID: 39831730
  8. 8

    Expanding the Spectrum of BCAP31-Associated Diseases: Early-Onset Parkinson Disease.

    Ishiguro M, Funayama M, Park DH, et al.

    Neurology. Genetics 2026; (12(4)):e200404 doi:10.1212/NXG.0000000000200404.

    PMID: 42312245

This page describes symptoms and monitoring considerations for BCAP31-related syndrome for informational purposes only and does not constitute medical advice. Ask your child’s healthcare team to interpret symptoms, test results, and urgent warning signs.

Guide contents Developmental malformations-deafness-dystonia syndrome
Research & Literature
02 The Science of BCAP31 04 Navigating the Diagnosis