SNP Shot: Genomic Insights

Pitt-Hopkins syndrome (PHS) is a genetic disorder characterized by several key features: intellectual disability, delayed development, breathing irregularities, recurrent seizures (epilepsy), and distinctive facial characteristics.

Individuals with PHS typically experience moderate to severe intellectual disability and significant delays in psychomotor development, impacting both mental and motor skills. This can manifest as difficulty learning to walk, impaired fine motor skills (e.g., grasping small objects), and limited speech development, with many individuals remaining nonverbal or only learning a few words. Many individuals with PHS also exhibit characteristics commonly associated with autism spectrum disorders, such as challenges with communication and social interaction.

A hallmark of PHS is the presence of breathing problems, characterized by alternating episodes of hyperventilation (rapid breathing) and apnea (periods of slowed or stopped breathing). These episodes can lead to reduced blood oxygen levels, potentially causing cyanosis (a bluish discoloration of the skin or lips) and, in some cases, loss of consciousness. Chronic low blood oxygen levels in some older individuals can result in digital clubbing, where the tips of the fingers and toes become widened and rounded. These breathing irregularities primarily occur during waking hours, typically emerging in mid-childhood, although they can appear earlier in infancy. Emotional triggers, such as excitement or anxiety, or even extreme fatigue can precipitate hyperventilation and apnea episodes.

Epilepsy is a common feature of PHS, with seizure onset usually occurring in childhood, though it can sometimes be present from birth.

People with PHS share distinctive facial features, including thin eyebrows, deep-set eyes, a prominent nose with a high bridge, a well-defined Cupid's bow (double curve) on the upper lip, a wide mouth with full lips, and widely spaced teeth. The ears are often thick and cup-shaped.

Children with PHS are often described as having a happy and excitable disposition, frequently smiling, laughing, and exhibiting hand-flapping movements. However, they may also experience anxiety and exhibit behavioral challenges.

Other potential features associated with PHS include constipation and other gastrointestinal issues, microcephaly (an unusually small head size), myopia (nearsightedness), strabismus (misaligned eyes), short stature, and minor brain abnormalities. Affected individuals may also have small hands and feet, a single palmar crease, pes planus (flat feet), or fleshy pads on the fingertips and toes. Males with PHS may experience cryptorchidism (undescended testes).

Inheritance:

PHS follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene in each cell is enough to cause the disorder.