SNP Shot: Genomic Insights

CHARGE syndrome is a complex condition impacting multiple body systems. The name "CHARGE" is an acronym representing common features: coloboma, heart defects, atresia choanae (or choanal atresia), growth retardation, genital abnormalities, and ear abnormalities. The specific combination and severity of these characteristics vary significantly among affected individuals. These numerous health issues can be life-threatening, particularly during infancy. Individuals diagnosed with CHARGE syndrome typically exhibit several major characteristics or a combination of major and minor characteristics.

The major characteristics of CHARGE syndrome are highly prevalent in this condition and comparatively rare in other disorders. Coloboma, a gap or hole in one or more eye structures formed during early development, is seen in most individuals. This can affect one or both eyes and may impact vision depending on the size and location of the coloboma. Some individuals also have microphthalmia, or abnormally small or underdeveloped eyes. Choanal stenosis (narrowing) or choanal atresia (complete blockage) of the nasal passages is frequently observed, leading to breathing difficulties. Cranial nerve abnormalities are also common. These nerves, originating directly from the brain, extend to the head and neck, controlling muscle movement and sensory information. Dysfunction of specific cranial nerves can cause problems with swallowing, facial paralysis, reduced or absent sense of smell (hyposmia/anosmia), and varying degrees of hearing loss. Ear abnormalities, both in the middle and inner ear, are typical and contribute to hearing impairment. External ear shape is also often unusual.

While the minor characteristics of CHARGE syndrome are common within the disorder, they can also be found in individuals without CHARGE. These include heart defects; slow growth beginning in late infancy; delays in motor skill development like sitting and walking; and cleft lip, with or without cleft palate. Hypogonadotropic hypogonadism, affecting hormone production related to sexual development, is common. Consequently, males often have micropenis (an unusually small penis) and cryptorchidism (undescended testes). Genital abnormalities are less frequently seen in females. Puberty may be delayed or incomplete in both males and females. Tracheoesophageal fistula, an abnormal connection between the esophagus and trachea, is another minor feature. Many individuals with CHARGE syndrome also display distinctive facial features, such as a square face and facial asymmetry (differences between the two sides of the face). Cognitive function varies widely, ranging from normal intelligence to significant learning disabilities with absent speech and poor communication skills.

Less frequently observed features of CHARGE syndrome include kidney abnormalities, immune system problems, abnormal spinal curvature (scoliosis or kyphosis), and limb abnormalities such as polydactyly (extra fingers or toes), oligodactyly (missing fingers or toes), clubfoot, and abnormalities of the long bones in the arms and legs.

Inheritance:

When CHARGE syndrome results from mutations in the CHD7 gene, it follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is needed to cause the disorder. Most cases are due to new mutations and occur in individuals with no family history of the condition. Rarely, an affected individual inherits the mutation from an affected parent. The inheritance pattern for other cases of CHARGE syndrome remains unknown.