User:Jshelby9/Pitt–Hopkins syndrome

Pitt–Hopkins syndrome (PTHS) is a rare genetic disorder characterized by developmental delay, epilepsy, distinctive facial features, and possible intermittent hyperventilation followed by apnea. It is part of the clinical spectrum of Rett-like syndromes. TCF4, which encodes a basic helix-loop-helix (bHLH) transcription factor, was identified as the gene responsible for de novo molecular defects. Even though PTHS appears to be a recognized clinical entity, it tends to go undiagnosed, especially when it is associated with less typical facial gestalt.

As more is learned about Pitt–Hopkins, the developmental spectrum of the disorder is widening, and can also include difficulties with anxiety, autism, ADHD, and sensory disorders. It is associated with an abnormality within chromosome 18; specifically, it is caused by an insufficient expression of the TCF4 gene.

PTHS has traditionally been associated with severe cognitive impairment, however true intelligence is difficult to measure given motor and speech difficulties. Thanks to augmentative communication and more progressive therapies, many individuals can achieve much more than initially thought. It has become clearer that there is a wider range of cognitive abilities in Pitt–Hopkins than reported in much of the scientific literature. Researchers have developed cell and rodent models to test therapies for Pitt–Hopkins.

PTHS is estimated to occur in 1:11,000 to 1:41,000 people.

Commonly Reported Dysmorphic Characteristics in Children:^{[citation needed]}

• Broad nasal bridge with bulbous tip
• Wide Mouth
• Cupid's bow philtrum
• Prominent Ears
• Flat feet
• Overriding toes
• Fetal Pads
• Short Stature
• Scoliosis

Adults with PTHS.

Adults who have PTHS may have trouble with their speech. Craniofacial features, which are important when diagnosing PTHS, become more visible as the person gets older.

PTHS is characterized by developmental delay, possible breathing problems of episodic hyperventilation and/or breath-holding while awake, recurrent seizures/epilepsy, gastrointestinal issues, and distinctive facial features. Stereotypic movements, particularly of the arms, wrists and fingers are almost universal. Hypotonia is common (75%), as is an unsteady gait. Other features include a single (simian) palmar crease, long, slender fingers, flat feet and cryptorchidism (in males). The presence of "fetal finger pads" is common. Hyperventilation may occur and is sometimes followed by apnea and cyanosis. Constipation is common. Microcephaly and seizures may occur. Hypopigmented skin macules have occasionally been reported. Individuals with Pitt–Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling and laughter.^{[citation needed]}

History

The condition was first described in 1978 by D. Pitt and I. Hopkins (The Children's Cottages Training Centre, Kew and Royal Children's Hospital, Melbourne, Australia) in two unrelated patients.

Professor Philip Beales, of the Institute of Child Health, has speculated that Peter the Wild Boy had Pitt–Hopkins syndrome. The boy was brought to Britain in 1725 as a feral child.^{[citation needed]}

PTHS predominantly arises from de novo mutations within the TCF4 gene locus, with rare instances of parental mosaicism.