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PubMed This is a summary of 16 peer-reviewed journal articles Updated
Neurology · Kernicterus Spectrum Disorder

The Biology and Symptoms of Kernicterus

At a Glance

Kernicterus Spectrum Disorder (KSD) is caused by dangerously high bilirubin levels that damage a newborn's brain. It results in four classic symptoms: movement disorders like dystonia, a specific type of hearing loss called ANSD, difficulty looking upward, and discolored or weakened baby teeth.

While neonatal jaundice is common, Kernicterus Spectrum Disorder (KSD) occurs when a specific type of bilirubin—unconjugated bilirubin—reaches dangerous levels in the blood. This “free” bilirubin is fat-soluble, which allows it to slip through the blood-brain barrier, the protective shield that normally keeps toxins out of the brain [1][2].

Once inside, bilirubin acts as a selective toxin. It does not damage the whole brain equally; instead, it targets specific areas that are highly active and sensitive during the first days of life. The most affected regions are the basal ganglia (specifically the globus pallidus), which controls movement, and the brainstem, which manages hearing and eye movements [3][4]. This selective damage results in a classic “tetrad” (a group of four) of symptoms.

1. Movement Disorders (Choreoathetosis and Dystonia)

Damage to the globus pallidus disrupts the brain’s “control center” for smooth movement. This leads to Dyskinetic Cerebral Palsy, which typically manifests in two ways:

  • Dystonia: Involuntary muscle contractions that cause twisting or repetitive movements and unusual postures [5].
  • Choreoathetosis: A combination of “chorea” (jerky, involuntary movements) and “athetosis” (slow, writhing movements), especially in the hands and feet [5][6].

2. Auditory Neuropathy Spectrum Disorder (ANSD)

KSD causes a very specific type of hearing challenge. Unlike typical hearing loss caused by structural damage to the inner ear (the cochlea), ANSD occurs because the bilirubin damages the nerve pathways that carry sound from the ear to the brain [7][8].

  • The “Hidden” Loss: A child with ANSD may pass a standard newborn hearing screen (like the OAE test) because their inner ear “hair cells” are often healthy [7].
  • The Clarity Issue: The ear picks up the sound, but the brain receives a scrambled or “static” signal. This makes it very difficult for the child to understand speech, even if they can hear that a sound is happening [9][10].

3. Oculomotor Dysfunction (Upward Gaze Palsy)

The brainstem contains the “wiring” for eye movements. Bilirubin toxicity often affects the nerves responsible for vertical sight.

  • Upward Gaze Palsy: The most common sign is an inability to look upward voluntarily [5][11].
  • Sunsetting Sign: In some infants, the eyes may appear to be driven downward, with the white of the eye showing above the iris, resembling a “setting sun” [5].

4. Dental Enamel Hypoplasia

Bilirubin can interfere with the cells that build tooth enamel (ameloblasts) while the primary (baby) teeth are still forming in the jaw [12].

  • Physical Changes: This can result in enamel hypoplasia, where the enamel is thin, pitted, or missing in certain areas [13].
  • Discoloration: Because bilirubin is a pigment, the teeth may erupt with a distinct yellowish or even greenish tint, known as “green teeth” (chlorodontia), though this discoloration may fade over time [5][6].

Why This Happens

At the cellular level, bilirubin causes a “perfect storm” of damage. It triggers oxidative stress (an imbalance of harmful molecules), neuroinflammation (swelling in the brain), and apoptosis (programmed cell death) [2][14]. Because the globus pallidus and auditory nerves are working so hard during the newborn period, they have the highest demand for energy, making them the first to fail when bilirubin levels become toxic [15][16].

Common questions in this guide

How does high bilirubin cause brain damage in kernicterus?
Unconjugated bilirubin can pass through the protective blood-brain barrier in infants. Once inside, it acts as a toxin that specifically damages highly active areas of a newborn's brain, such as the basal ganglia and brainstem.
What movement problems are associated with kernicterus?
Children with kernicterus often develop dyskinetic cerebral palsy. This can appear as dystonia, which causes involuntary muscle twisting and unusual postures, or choreoathetosis, which involves jerky and slow, writhing movements.
Why did my child pass a newborn hearing screen but still have hearing issues?
Kernicterus can cause Auditory Neuropathy Spectrum Disorder. This means the inner ear is healthy and can pass standard newborn screens, but the nerve pathways carrying sound to the brain are damaged, making speech scrambled and hard to understand.
What are sunsetting eyes in infants?
Sunsetting eyes occur when nerve damage in the brainstem prevents an infant from looking upward voluntarily. The eyes appear driven downward with the white of the eye showing above the colored iris, resembling a setting sun.
Can high bilirubin affect my baby's teeth?
Yes, bilirubin can interfere with the cells that build baby teeth while they are forming in the jaw. This can lead to thin, pitted enamel, and the teeth may erupt with a temporary yellowish or greenish tint.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Can you explain where specifically in the basal ganglia my child's brain was affected and how that correlates to their movement patterns?
  2. 2.My child has passed an OAE (Otoacoustic Emissions) test; does this mean they are still at risk for Auditory Neuropathy Spectrum Disorder (ANSD)?
  3. 3.How do the 'sunsetting' eyes or upward gaze palsy specifically relate to the brainstem injury caused by bilirubin?
  4. 4.What are the best dental care practices to protect my child's teeth if they have enamel hypoplasia?
  5. 5.Is the movement disorder we are seeing classified as dystonia, choreoathetosis, or a combination of both?

Questions For You

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References

References (16)
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    Review of bilirubin neurotoxicity I: molecular biology and neuropathology of disease.

    Riordan SM, Shapiro SM

    Pediatric research 2020; (87(2)):327-331 doi:10.1038/s41390-019-0608-0.

    PMID: 31600770
  2. 2

    Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1 -/- mouse model.

    Vodret S, Bortolussi G, Jašprová J, et al.

    Journal of neuroinflammation 2017; (14(1)):64 doi:10.1186/s12974-017-0838-1.

    PMID: 28340583
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    Association of T1-weighted hyperintensity with timing of peak bilirubin levels in neonates with hyperbilirubinemia.

    Wang R, Tian H, Ren Z, et al.

    Neuroradiology 2025; (67(10)):3049-3059 doi:10.1007/s00234-025-03690-2.

    PMID: 40586872
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    Acute and Chronic Kernicterus: MR Imaging Evolution of Globus Pallidus Signal Change during Childhood.

    Gburek-Augustat J, Sorge I, Stange M, et al.

    AJNR. American journal of neuroradiology 2023; (44(9)):1090-1095 doi:10.3174/ajnr.A7948.

    PMID: 37620154
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    Childhood neurodevelopmental outcomes of survivors of acute bilirubin encephalopathy: A retrospective cohort study.

    Kumar V, Kumar P, Sundaram V, et al.

    Early human development 2021; (158()):105380 doi:10.1016/j.earlhumdev.2021.105380.

    PMID: 33990043
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    Bilirubin Encephalopathy.

    Qian S, Kumar P, Testai FD

    Current neurology and neuroscience reports 2022; (22(7)):343-353 doi:10.1007/s11910-022-01204-8.

    PMID: 35588044
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    Prevalence and Auditory Characteristics of Auditory Neuropathy Spectrum Disorder in Adult Population with Sensory Neural Hearing Loss: A Hospital Based Study in South India.

    Muthukumar R, Jaya V, Vignesh SS, Thenmozhi K

    Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India 2023; (75(3)):1906-1911 doi:10.1007/s12070-023-03766-6.

    PMID: 37636754
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    Auditory Neuropathy Spectrum Disorder in the White Sutton Syndrome.

    Musumano LB, Fancello V, Negossi L, et al.

    The journal of international advanced otology 2023; (19(3)):260-262 doi:10.5152/iao.2023.22877.

    PMID: 37272646
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    Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia.

    Gökdoğan Ç, Genç A, Gülbahar Ö, et al.

    Brazilian journal of otorhinolaryngology 2016; (82(2)):144-50.

    PMID: 26727606
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    Postoperative Intracochlear Electrocochleography in Pediatric Cochlear Implant Recipients: Association to Audiometric Thresholds and Auditory Performance.

    Attias J, Ulanovski D, Hilly O, et al.

    Ear and hearing 2020; (41(5)):1135-1143 doi:10.1097/AUD.0000000000000833.

    PMID: 31977726
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    A zebrafish model for studying the mechanisms of newborn hyperbilirubinemia and bilirubin-induced neurological damage.

    Guzelkaya M, Onal E, Gelinci E, et al.

    Frontiers in cell and developmental biology 2023; (11()):1275414 doi:10.3389/fcell.2023.1275414.

    PMID: 38033855
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    DENTAL ENAMEL FORMATION AND IMPLICATIONS FOR ORAL HEALTH AND DISEASE.

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    Physiological reviews 2017; (97(3)):939-993 doi:10.1152/physrev.00030.2016.

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    Oral manifestations of gastrointestinal diseases in children. Part 4: Coeliac disease.

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    PMID: 28045325
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    Inhibition of Microglial Activation Ameliorates Inflammation, Reduced Neurogenesis in the hippocampus, and Impaired Brain Function in a Rat Model of Bilirubin Encephalopathy.

    Zhang Y, Li S, Li L, et al.

    Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 2024; (19(1)):23 doi:10.1007/s11481-024-10124-y.

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    Bilirubin Triggers Calcium Elevations and Dysregulates Giant Depolarizing Potentials During Rat Hippocampus Maturation.

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    Effects of Repetitive Transcranial Magnetic Stimulation on Pallidum GABAergic Neurons and Motor Function in Rat Models of Kernicterus.

    Wang N, Jia Y, Zhou X, et al.

    Brain sciences 2023; (13(9)) doi:10.3390/brainsci13091252.

    PMID: 37759853

This page explains the symptoms and biology of Kernicterus Spectrum Disorder for educational purposes. Always consult a pediatric neurologist or healthcare provider for an accurate diagnosis and symptom management for your child.

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