Pitt-Hopkins syndrome is a rare genetic disease that stems from mutations in the transcription factor 4 (TCF4) gene located on chromosome 18. The clinical presentation encompasses diverse features, some of the most important being facial changes, mental and growth retardation, epilepsy, respiratory difficulties, and deficits of motor control. Pitt-Hopkins syndrome is assumed to be transferred through an autosomal dominant pattern, but de novo mutations do occur as well. The diagnosis is made through a detailed clinical workup and molecular genetic studies.
Despite the rare occurrence of Pitt-Hopkins syndrome in clinical practice, signs and symptoms have been well-established in previous years      :
Other notable manifestations are epilepsy (usually appearing in later stages of the disease), nystagmus, constipation, poor activity of the motor system (children start walking around 6 years of age, while head movement and fine motor skills are affected as well), and stereotypic movements of hands and the head     . The movements are seen in up to 80% of cases and it is assumed that hand clapping, wringing, swaying, or flapping of the hands are attempts to achieve communication . Many reports describe children who suffer from Pitt-Hopkins syndrome as happy and sociable, with only occasional signs of anxiety and aggression, although they may exhibit excessive sleeping  .
Because of the distinct clinical findings encountered in these patients, the physician plays a key role in raising suspicion. A properly obtained history and a thorough physical examination can showcase relevant attributes. A family history can provide crucial details for recognizing Pitt-Hopkins syndrome in parents and close relatives (given the presumed autosomal dominant pattern of inheritance), further solidifying the diagnosis. The workup should include electroencephalography (EEG) and magnetic resonance imaging (MRI), which can highlight hypoplasia of the frontal lobes, hippocampus, and corpus callosum, ventricular enlargement, and pronounced hyperintensity signaling of white matter in the temporal lobes in many patients   . To confirm the condition, however, employment of molecular genetic studies is needed. Whole-exome sequencing and chromosomal analysis are procedures that are able to identify TCF4 mutations of chromosome 18  . Some studies have advocated TCF4 mutation testing in people who are diagnosed with other similar diseases that have no genetic confirmation, such as Angelman syndrome, Rett syndrome, and Mowat-Wilson syndromes, mainly to prevent a missed diagnosis .