Pitt–Hopkins syndrome (PTHS) is a rare genetic disorder characterized by developmental delay, moderate to severe intellectual disability,[1] distinctive facial features, and possible intermittent hyperventilation followed by apnea.

[6] Those with PTHS have reported high rates of self-injury and aggressive behaviors usually related to autism and their sensory disorders.

[7] PTHS has traditionally been associated with severe cognitive impairment, however true intelligence is difficult to measure given motor and speech difficulties.

[11]Other features of Pitt-Hopkins syndrome may include constipation and other gastrointestinal problems, an unusually small head (microcephaly), nearsightedness (myopia), eyes that do not look in the same direction (strabismus), short stature, and minor brain abnormalities[12] Adults who have PTHS may have trouble with their speech.

[9] Children with Pitt-Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements.

[13] Gastrointestinal difficulties are common in individuals with Pitt-Hopkins and can include constipation, reflux, and burping.

[14] Magnetic resonance imaging (MRI) reveals that deviations in the brain may occur in individuals with Pitt-Hopkins.

These can include a small corpus callosum, wide ventricles, and deviations in the posterior fossa.

Minor hand and foot anomalies such as slender or small hands and feet, broad fingertips, clinodactyly, tapered fingers, transverse palmar crease, flat feet with hindfoot valgus deformity, overriding toes, and short metatarsals have been reported.

In one individual an absent thumb tendon was found during surgery [Authors, personal observation].

The risk in siblings is low, but higher than the general population due to parental germline mosaicism.

[9] A Pitt–Hopkins-like 1 phenotype has been assigned to autosomal recessive mutations of the contactin associated protein like 2 (CNTNAP2) gene on the long arm of chromosome 7 (7q33-q36) and a Pitt-Hopkines-like 2 phenotype has been assigned to autosaml recessive mutations of the neurexin 1 alpha (NRXN1) gene on the short arm of chromosome 2 (2p16.3).

These include a hypoplastic corpus callosum with a missing rostrum and posterior part of the splenium, with bulbous caudate nuclei bulging towards the frontal horns.

[4] Recommendations for developmental delay and intellectual disability in the U.S. (may differ depending on country):[9] 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.