Crainiofacial

• Hypertelorism – A greater than normal distance between the pupils of the eyes
• Downward slanting Palprebral fissures –
  The opening between the eyelids is narrow and slants downward from inner corner to outer corner
• Thick septum – A broad nose with a thicker than normal area between the nostrils
• Everted lips – Large mouth with full, turned out lips
• Prominent, low-set ears
• Ptosis – Fullness of the upper eyelids
• Prominent eyebrow ridges
• Thickened skull with large frontal sinuses [1]

Hands

• Short, tapered fingers
• Tufting of distal phalanges (only visible on X-ray)
• Puffy hands – soft, elastic skin
• Short, curved fingernails
• Hypothenar crease (short, horizontal line in palm of hand below little finger) [1] [4]

Cognitive / Behavior

• Severe intellectual disability in most cases – rarely, mild to moderate
• Pleasant personality – their good loving temperament remains intact throughout life
• Females have a higher rate of psychiatric illness than the general population
• Speech is typically affected but to varying degrees
• Some autistic-like behaviors
• Can occasionally be frustrated due to lack of and understanding needs (communication challenges) [1] [4]

Mobility

• Sitting, crawling and walking are delayed
• Challenges with fine and gross motor coordination
• Loss of strength and muscle mass
• Ataxic gait
• Both decreased and increased deep tendon reflexes
• Progressive spasticity
• Progressive paraplegia with loss of ability to walk, due to calcification of the ligamenta flava and congenital stenosis (narrowing) of the spinal canal
• Sensory integration issues and sensory defensiveness, most noticeable in early childhood
• SIDEs (Stimulus Induced Drop Episodes) Stimulus-induced Drop Episodes may progress the need to utilize a wheelchair for mobility due to safety concerns. [1]

Teeth and Mouth

Dental anomalies are common and may include:

• High, narrow palate
• Small, widely-spaced peg-shaped baby teeth
• Midline lingual furrow (midline groove in tongue)
• Malocclusion (“bad bite”)
• Early loss of baby teeth
• Late eruption of primary teeth
• Missing permanent teeth
• Small jaw
• Obstructive sleep apnea

Psychiatric Disorders

Twenty families have reported individuals (mostly females) with CLS showing episodic or long standing psychotic behavior. In one instance this resulted in hospitalization for over 30 years. In another family, one woman was described as being “shy and retiring” whereas her sister had a life long history of being “in a world of her own”. Three other affected females in two different families have been diagnosed as having either schizophrenia or a depressive psychosis. In a different family, a young woman became very delusional. With immunotherapy and other medications, she fully recovered from her cognitive decline and psychosis.  Given the relative rarity of CLS, these reports indicate psychotic behavior may be a characteristic rather than a spurious observation. Onset seems to appear around the age of 20 years. Response to current therapies is variable. While it appears to be more prevalent in females, a few males with CLS have also been reported to have some kind of neuropsychiatric regression. [5]