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Clinical Characteristics

Features of CLCN4 related genetic disorder

Male individuals with a CLCN4-related disorder will have some degree of developmental delay/ intellectual disability. The severity of learning difficulty can also vary within individuals with the same CLCN4 gene change, even within the same family.  Females who carry a CLCN4 gene changes have been reported to have normal intelligence, borderline intellectual disability/ learning difficulties, or more severe intellectual disability.  Intellectual disability is more common in females if the genetic change is a new genetic change for that individual (‘de novo’ change), rather than an inherited genetic change

It is relatively common for individuals with a CLCN4 related condition to have particular delays in their speech and language development.  Some individuals have ongoing speech difficulties causing stutters indistinct speech (articulation difficulties).

Autistic behaviours have been reported in some individuals with CLCN4 gene changes. Other behavioural differences reported in some people with CLCN4 gene changes include a degree of hyperactivity, aggression and/or mood swings. Other individuals are described to be more introverted or have no significant behavioural issues.  There is probably an increased chance of mental health conditions (for example anxiety and depression) in both males and females with a CLCN4 gene change.

Approximately, 50% of individuals with a CLCN4 disorder will have seizures. These may not be a major concern and easy to treat with medication. However some patients have severe seizure patterns (epileptic encephalopathies). Some individuals have been described to have difficulties with an unsteady gait (ataxia) or have increased reflexes in their limbs and a tendency to walk on their toes (lower limb spasticity). Other individuals have a completely normal neurological examination. Many individuals with a CLCN4 related condition were described as being quite floppy as a baby (infantile hypotonia). Some older individuals with CLCN4 related condition have had brain imaging suggestive of a smaller brain size with age (cortical atrophy) or changes in the appearance of the white matter in their brains. Other individuals have had normal brain imaging.

Some adult males with CLCN4 related disorder have been described as having a slightly longer face with a more prominent chin, but generally individuals do not look significantly different from other (unaffected) members of their family and we are not aware of a particularly increased chance of other medical conditions.

Most of these features become present by early childhood. This is a genetic condition and is not related to environmental exposures or events during pregnancy or in early infant life.