Coffin-Lowry syndrome

Coffin-Lowry syndrome is an X-linked genetic condition. It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis. It affects both sexes, but is generally much more severe in males; females can have a highly variable phenotype ranging from mild manifestations to significant intellectual disability. A distinctive presentation may include the combination of downslanted palpebral fissures, a bulbous nose, tapering fingers, and stimulus-induced drop episodes.

It can present with psychiatric features such as behavioural difficulties, hyperactivity, ADHD, anxiety, aggression, and, less commonly, mood or other psychiatric disorders. Autism spectrum disorder (ASD) has also been described. Psychiatric and behavioural manifestations can persist into adulthood, particularly in females with milder overall phenotypes, although the syndrome is usually recognised during childhood because of developmental and intellectual difficulties.

From a morphologic lens perspective, other features include (but are not limited to):

• Prominent supraorbital ridges

• Coarse face

• Midface retrusion

• Widely spaced eyes

• Downslanted palpebral fissures

• Protruding ears

• Thick vermilion

• Widely spaced teeth

Other characteristic features include intellectual disability and developmental delay, short stature, and progressive skeletal abnormalities including kyphoscoliosis and pectus deformity. A particularly distinctive neurological feature is stimulus-induced drop episodes, in which sudden emotional excitement or unexpected sensory stimuli can trigger brief episodes of loss of muscle tone and collapse. Seizures, hypotonia, microcephaly, and, less commonly, progressive neurological complications such as paraplegia may also occur.

Early diagnosis is important to identify intellectual, behavioural, neurological, and skeletal complications; to distinguish stimulus-induced drop episodes from epileptic seizures or other causes of collapse; and to allow appropriate developmental, behavioural, educational, neurological, cardiac, hearing, and musculoskeletal surveillance and support.