CHIME syndrome

CHIME Syndrome
Synonyms	Zunich–Kaye Syndrome
Pronounce	N/A
Specialty	N/A
Symptoms	Coloboma, Heart defects, Ichthyosiform dermatosis, Intellectual disability, Ear anomalies
Complications	N/A
Onset	Congenital
Duration	Lifelong
Types	N/A
Causes	Autosomal recessive mutation in PIGL gene
Risks	N/A
Diagnosis	Clinical evaluation, Genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Supportive care
Medication	N/A
Prognosis	N/A
Frequency	Extremely rare
Deaths	N/A

CHIME syndrome

CHIME Syndrome, also known as Zunich–Kaye Syndrome, is a rare autosomal recessive genetic disorder characterized by a constellation of congenital anomalies, primarily affecting the eyes, heart, skin, nervous system, and ears. The acronym CHIME represents the core clinical features:

• C – Coloboma (ocular defect)
• H – Heart defects
• I – Ichthyosiform dermatosis (scaly skin)
• M – Intellectual disability
• E – Ear anomalies

Signs and Symptoms

The clinical presentation of CHIME Syndrome is variable, but the following features are commonly observed:

Craniofacial and Ocular Features

• Coloboma – Congenital defect in the eye affecting the iris, retina, choroid, or optic nerve.
• Facial dysmorphism – Wide nasal bridge, low-set ears, hypertelorism (widely spaced eyes).
• Strabismus – Misalignment of the eyes.
• Microphthalmia – Small or underdeveloped eyes.

Cardiac Features

• Congenital heart defects, such as:
• Atrial septal defect (ASD)
• Ventricular septal defect (VSD)
• Patent ductus arteriosus (PDA)

Dermatological Features

• Ichthyosiform dermatosis – Dry, scaly, thickened skin, resembling ichthyosis.
• Erythema – Persistent redness of the skin.

Neurological and Developmental Features

• Intellectual disability – Ranging from mild to severe cognitive impairment.
• Hypotonia – Decreased muscle tone.
• Seizures – Reported in some cases.
• Global developmental delay – Delayed milestones in speech, motor function, and learning abilities.

Ear and Hearing Anomalies

• Low-set, malformed ears
• Hearing loss – May be sensorineural or conductive.

Genetics and Pathophysiology

CHIME Syndrome is caused by mutations in the PIGL gene, located on chromosome 17q12.

• PIGL encodes an enzyme involved in glycosylphosphatidylinositol (GPI) anchor biosynthesis, which is crucial for cell membrane protein attachment.
• Mutations disrupt protein anchoring, leading to abnormal development of multiple organ systems.

The condition follows an autosomal recessive inheritance pattern, meaning:

• Two copies of the mutated gene (one from each parent) are required to manifest the disorder.
• Parents are typically asymptomatic carriers.

Diagnosis

Clinical Evaluation Diagnosis is primarily clinical, based on the characteristic combination of:

• Ophthalmologic examination (coloboma)
• Cardiac assessment (echocardiogram)
• Skin biopsy (ichthyosiform dermatosis)
• Neurological evaluation (intellectual disability, developmental delay)

Genetic Testing

• Whole exome sequencing can confirm PIGL mutations.
• Targeted genetic analysis for suspected familial cases.

Differential Diagnosis

Conditions that mimic CHIME Syndrome include:

• CHARGE syndrome – Similar coloboma and heart defects but different genetic cause.
• Neu-Laxova syndrome – Severe congenital ichthyosis with neurodevelopmental defects.
• Conradi–Hünermann syndrome – Ichthyosis and skeletal abnormalities.

Treatment and Management

There is no cure for CHIME Syndrome, and treatment is supportive and symptomatic:

Ophthalmic Management

• Regular ophthalmologic follow-ups to monitor coloboma-related vision loss.
• Corrective lenses or surgery for strabismus.

Cardiac Care

• Surgical correction for congenital heart defects (if needed).
• Echocardiographic monitoring.

Dermatological Care

• Emollients and keratolytics for ichthyosiform dermatosis.
• Topical retinoids to reduce skin scaling.

Developmental and Neurological Support

• Speech therapy, occupational therapy, and physical therapy for developmental delays.
• Antiepileptic drugs (AEDs) if seizures occur.

Hearing Support

• Hearing aids or cochlear implants if significant hearing loss is present.

Prognosis

• Lifelong condition with variable severity.
• Early intervention and supportive therapies improve quality of life.
• Cardiac anomalies and neurological complications influence overall prognosis.

Epidemiology

• Extremely rare, with only a few documented cases worldwide.
• No known ethnic or geographical predisposition.

See Also

• CHARGE syndrome
• Ichthyosis
• Congenital heart defects
• Intellectual disability

NIH genetic and rare disease info

• NIH info on CHIME syndrome

CHIME syndrome is a rare disease.