Pitt–Hopkins syndrome

PTHS can be seen as early as childhood. The earliest signs in infants is the lower face and the high nasal root. The facial features are characteristic and include: • Broad nasal bridge with bulbous tip • Wide mouth • Cupid's bow philtrum • Prominent ears • Thin eyebrows Flat feet, overriding toes, and fetal pads are also common. Adults who have PTHS may have trouble with their speech. Gastrointestinal Gastrointestinal difficulties are common in individuals with Pitt-Hopkins and can include constipation, reflux, and burping. Severe constipation often occurs over the entire lifespan. Breathing issues may cause air swallowing and associated pain. Low muscle tone can cause feeding issues at an early age. ==Genetics==

The genetic cause of this disorder was described in 2007. This disorder is due to a haploinsufficiency of the transcription factor 4 (TCF4) gene which is located on the long arm of chromosome 18 (18q21.2) The mutational spectrum appears to be 40% point mutations, 30% small deletions/insertions and 30% deletions. All appear to be de novo mutations. The risk in siblings is low, but higher than the general population due to parental germline mosaicism. Pitt-Hopkins-like 1 is ultra-rare, with an estimated prevalence of less than 1 in a million. Malformations in the CNS can be seen in about 60 to 70% of patients on MRI scans. Pitt–Hopkins patients with a TCF4 deletion can lack the syndrome's characteristic facial features. ==Diagnosis==

There is not a certain diagnostic criteria, but there are a few symptoms that support a diagnosis of PTHS. Some examples are: facial dysmorphism, early onset global developmental delay, moderate to severe intellectual disability, breathing abnormalities, and a lack of other major congenital abnormalities. It is possible that a phenotype resembling PTHS can occur without the mutation in the TCF4 gene. Mutations in the TCF4 gene do not always result in stereotypical Pitt-Hopkins syndrome. When a patient is suspected of having PTHS, genetic tests looking at the TCF4 gene are typically done. Differential diagnosis PTHS is symptomatically similar to Angelman syndrome, Rett syndrome, Skraban–Deardorff syndrome and Mowat–Wilson syndrome. Angelman syndrome most closely resembles PTHS. Both have absent speech and a "happy" disposition. Of the differentials, Rett syndrome is the least close to PTHS. This syndrome is seen as a progressive encephalopathy. Both Angelman syndrome and Rett syndrome lack the distinctive facial features of PTHS. Mowat–Wilson syndrome is seen in early infancy and is characterized by distinctive facial abnormalities. ==Treatment==

There is no specific treatment for this condition. It is based on symptomatology. Since there is a lack of treatment, people with PTHS use behavioral and training approaches. Comorbidities may also be treated. Care from a medical team including neurologists, ophthalmologists, pulmonologists, and gastroenterologists may be utilized. Recommendations for developmental delay and intellectual disability in the U.S. (may differ depending on country): • Early intervention program from newborn to age 3 will allow access to different therapies (occupational, physical, speech, and feeding). • Developmental preschool through public school systems from ages 3 to 5. The child will need an evaluation before getting into the program, to see what kind of therapy is needed. • From the ages 5–21 the child's school may create an IEP (based on the child's functions and needs). Children are encouraged to stay in school until at least the age of 21. ==History==

, showing some of the physical traits of Pitt–Hopkins syndrome, including coarse, curly hair, drooping eyelids and large, thick-lipped mouth 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. == References ==