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Pitt-Hopkins Syndrome - TCF4

Clinical Features

Pitt-Hopkins Syndrome is characterized by a combination of severe mental retardation and certain facial dysmorphisms, accompanied in many cases by breathing abnormalities (episodes of sudden tachypnea and hyperventilation, followed by apnea and cyanosis). Patients also often develop epilepsy, microcephaly, and postnatal microsomia. Absence of speech development is common. Male and female children appear to be equally affected.
Due to phenotypical similarities, Pitt-Hopkins Syndrome represents an important differential diagnosis, especially for Rett and Angelman syndromes, but also for Mowat-Wilson syndrome.

• Craniofacial dysmorphisms:

Microcephaly
High cheekbones
Deep-set eyes, strabismus, narrow eyebrows
Wide, down-bowed nose with a prominent root and wide nostrils
Wide mouth with a cupid's bow-formed, mucous membrane upper lip and everted mucous membrane bottom lip
Widely spaced teeth, wide gums
Dysplastic and often wide ear helix
Prominent lower jaw
Facial abnormalities become more obvious with age.

• Neurological abnormalities:

Pronounced motor and mental retardierung, absence of speech development
epilepsy
Muscle hypotonia and/or ataxia
MRT: agenesia or hypoplasia of the Corpus callosum, "bulging" of the Nuclei caudati, ventricle asymmetry, atrophy of the frontal and parietal Cortex, as well as arachnoidal cysts.

• Vegetative symptoms:

More than half of all affected patients have breathing irregularities
In some cases, pronounced tendency toward constipation

The literature reports that patients with Pitt-Hopkins syndrome are prevailingly happy and show no pronounced signs of behavioral abnormalities.

Genetic Information

Pitt-Hopkins Syndrome follows an autosomal dominant pattern of inheritance and is caused by heterozygous de novo mutations in the TCF4 gene (Transscription factor 4, Chromosome 18, 18q21), which lead to haploinsufficiency in this gene.

Prevalence

Rare

Diagnostic