Zunich–Kaye syndrome (CHIME syndrome)

CHIME syndrome, also known as Zunich neuroectodermal syndrome, is an extremely rare genetic disorder characterized by a combination of congenital neurological abnormalities, distinctive facial features, and skeletal anomalies.

Key features:

• Coloboma: A coloboma is a gap or notch in one of the structures of the eye, such as the iris, retina, or optic nerve. In CHIME syndrome, colobomas can affect one or both eyes and may lead to visual impairment.
• Heart Defects: Congenital heart defects may be present in individuals with CHIME syndrome, including abnormalities of the heart structure or function.
• Ichthyosis: Ichthyosis refers to a group of skin disorders characterized by dry, scaly, and thickened skin. In CHIME syndrome, ichthyosis may be present from birth and can affect large areas of the body.
• Mental Retardation: Intellectual disability or developmental delay is a common feature of CHIME syndrome, affecting cognitive function and adaptive skills.
• Ear Anomalies: Ear anomalies, such as malformed or low-set ears, hearing loss, or absence of the external ear canal (aural atresia), may be present in individuals with CHIME syndrome.

Symptoms:

In addition to the characteristic features represented by the CHIME acronym, individuals with CHIME syndrome may exhibit a range of other clinical manifestations, including:

• Distinctive facial features, such as a broad forehead, hypertelorism (increased distance between the eyes), a flattened nasal bridge, and a wide nasal tip.
• Skeletal abnormalities, including joint contractures, scoliosis (curvature of the spine), and abnormalities of the hands and feet.
• Neurological abnormalities, such as seizures, hypotonia (low muscle tone), and developmental delay.
• Growth retardation and failure to thrive in some cases.

Causes:

CHIME syndrome is caused by mutations in the CHIME gene (also known as the PIGL gene), which is involved in the synthesis of glycosylphosphatidylinositol (GPI) anchors. GPI anchors are essential for attaching certain proteins to the cell membrane. Mutations in the CHIME gene disrupt the normal function of GPI anchors, leading to the characteristic features of the syndrome.

Diagnosis:

Diagnosis of CHIME syndrome is based on clinical evaluation, including assessment of the characteristic features and identification of associated abnormalities. Genetic testing may be performed to confirm the diagnosis by finding mutations in the CHIME gene.

Treatment:

Treatment of CHIME syndrome is primarily supportive and aims to address the individual's specific symptoms and medical needs. This may include interventions such as physical therapy to address skeletal abnormalities and improve mobility, educational interventions to support developmental progress and intellectual functioning, and medical management of associated health issues such as heart defects or ichthyosis. Early intervention services and multidisciplinary care involving specialists such as ophthalmologists, cardiologists, dermatologists, and developmental pediatricians may be beneficial for optimizing outcomes and quality of life for affected individuals.