Pitt-Hopkins Syndrome

Classification according to ICD-10
Q87.0	Congenital malformation syndromes with predominant involvement of the face
ICD-10 online (WHO version 2019)

The Pitt-Hopkins syndrome is a very rare genetic disease with the main features of an intellectual deficit , characteristic facial abnormalities and abnormal and irregular breathing .

Synonyms are: PTHS; English ENCEPHALOPATHY, SEVERE EPILEPTIC, WITH AUTONOMIC DYSFUNCTION; MENTAL RETARDATION, SYNDROMAL, WITH INTERMITTENT HYPERVENTILATION

The name refers to the first description from 1978 by the Australian doctors D. Pitt and I. Hopkins . The TCF4 gene could only be identified in 2007.

distribution

The frequency is given as less than 1: 1 million, men and women are equally affected, and so far fewer than 200 cases have been officially confirmed worldwide. The inheritance is autosomal dominant .

root cause

The disease is based on mutations in the TCF4 gene at gene location 18q21, which codes for a b-HLH transcription factor . In some documented cases, this gene is absent at all, leading to the chromosome 18 abnormality.

Clinical manifestations

The disease is characterized by:

mental retardation, lack of language acquisition
Motor development disorders with hypotonia
abnormal facial features such as macrostomy , large tooth gaps, broad palate, plump lips, deep-set eyes
Breathing disorders from early childhood or adolescence , attacks of hyperventilation

As a result of this genetic defect, patients often suffer from delayed growth and poor language skills.

Often occur constipation and gastroesophageal reflux on.

Diagnosis

The diagnosis is based on clinical findings, changes in the EEG . Image factor is found in the magnetic resonance imaging , a reduction in volume of the hippocampus and changes in the temporal lobe

Differential diagnosis

To be differentiated are the Angelman syndrome , the Kleefstra syndrome , the Rett syndrome and the Mowat-Wilson syndrome .

treatment

The therapy is multidisciplinary and includes physiotherapy, occupational therapy and speech therapy as well as hippotherapy and music therapy. Medication with acetazolamide has been described as successful.

literature

JD Sweatt: Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription. In: Experimental & molecular medicine. Vol. 45, 2013, p. E21, doi: 10.1038 / emm.2013.32 , PMID 23640545 , PMC 3674405 (free full text) (review).
M. Peippo, J. Ignatius: Pitt-Hopkins Syndrome. In: Molecular syndromology. Vol. 2, No. 3-5, April 2012, pp. 171-180, PMID 22670138 , PMC 3366706 (free full text).

Individual evidence

↑ ^a ^b ^c Pitt-Hopkins syndrome. In: Orphanet (Rare Disease Database).
↑ D. Pitt, I. Hopkins: A syndrome of mental retardation, wide mouth and intermittent overbreathing. In: Australian pediatric journal. Vol. 14, No. 3, September 1978, pp. 182-184, PMID 728011 .
↑ Italian Journal of Padiatrics, Pitt-Hopkins syndrome: report of a case with a TCF4 gene mutation , as of September 7, 2015
↑ OMIM | 160954 | Pitt-Hopkins syndrome
↑ C. Gaffney, P. McNally: Successful use of acetazolamide for central apnea in a child with Pitt-Hopkins syndrome. In: American journal of medical genetics. Part A. Vol. 167, No. 6, June 2015, p. 1423, doi: 10.1002 / ajmg.a.37034 , PMID 25900839 .

Web links

[Orpha-1] Pitt-Hopkins syndrome. In: Orphanet (Rare Disease Database).

[2] D. Pitt, I. Hopkins: A syndrome of mental retardation, wide mouth and intermittent overbreathing. In: Australian pediatric journal. Vol. 14, No. 3, September 1978, pp. 182-184, PMID 728011 .

[3] Italian Journal of Padiatrics, Pitt-Hopkins syndrome: report of a case with a TCF4 gene mutation , as of September 7, 2015

[4] OMIM | 160954 | Pitt-Hopkins syndrome

[5] C. Gaffney, P. McNally: Successful use of acetazolamide for central apnea in a child with Pitt-Hopkins syndrome. In: American journal of medical genetics. Part A. Vol. 167, No. 6, June 2015, p. 1423, doi: 10.1002 / ajmg.a.37034 , PMID 25900839 .