“Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series,” – January 10, 2018

Authors: Kimberly Goodspeed, MD , Cassandra Newsom, PsyD, Mary Ann Morris, PhD, BCSE, Craig Powell, MD, PhD, Patricia Evans, MD, PhD, Sailaja Golla, MD

Abstract: Pitt-Hopkins syndrome (PTHS) is a rare, genetic disorder caused by a molecular variant of TCF4which is involved in embryologic neuronal differentiation. PTHS is characterized by syndromic facies, psychomotor delay, and intellectual disability. Other associated features include early-onset myopia, seizures, constipation, and hyperventilation-apneic spells. Many also meet criteria for autism spectrum disorder. Here the authors present a series of 23 PTHS patients with molecularly confirmed TCF4 variants and describe 3 unique individuals. The first carries a small deletion but does not exhibit the typical facial features nor the typical pattern of developmental delay. The second exhibits typical facial features, but has attained more advanced motor and verbal skills than other reported cases to date. The third displays typical features of PTHS, however inherited a large chromosomal duplication involving TCF4 from his unaffected father with somatic mosaicism. To the authors’ knowledge, this is the first chromosomal duplication case reported to date.

See full paper: Journal of Child Neurology Pitt-Hopkins Syndrome


“Phenotype and natural history in 101 individuals with Pitt-Hopkins syndrome through an internet questionnaire system,” Orphanet Journal of Rare Diseases (2016) 11:37 

Authors: Channa F. de Winter, Melanie Baas, Emilia K. Bijlsma, John van Heukelingen, Sue Routledge and Raoul C. M. Hennekam.

Methods: We have built a waihonapedia system in a collaboration between physicians, social scientists, and parent support groups. The system consists of an initial extensive questionnaire for background cross-sectional data, and subsequent follow-up using small questionnaires, with a particular focus on behavioural aspects. The system was built to be used through the internet, ensuring a secure environment, respecting privacy for participants, and acting automated to allow for low costs and limiting human mistakes in data handling. Recruitment of participants is through the patient support groups. In addition, as a sub-study, we used the data from the waihonapedia system to compare the two proposed diagnostic classification systems for PTHS.

Results: We present here the results of the initial, cross-sectional questionnaire in which early development, physical health, cognition and behaviour are interrogated, and to which modules specific for PTHS were added on epilepsy and breathing patterns. We describe 101 individuals with a molecularly confirmed diagnosis of PTHS.
Comparison of the two classification systems aimed at helping the clinical diagnosis was performed in 47 of the present PTHS individuals, with disappointing results for both. Internationally accepted clinical diagnostic criteria are needed.

See Full article: DeWinter PTHS OrphanJRareDis2016