Case report: Pitt-Hopkins like syndrome with CNTNAP2 mutation

Sawsan Albaazi,Hula Shareef

doi:10.1186/s43042-020-00113-0

Abstract

BackgroundPitt-Hopkins syndrome (PHS) is a rare cause of severe intellectual disability, seizures, language impairment, and peculiar facial dysmorphism. It is caused by a mutation in transcription factor 4 (TCF4). Through molecular karyotyping and mutational analysis, a study identified recessive defects in two genes, contactin associated protein like 2 (CNTNAP2) and Neurexin I (NRXN1), in patients with similar presentations of Pitt-Hopkins syndrome and called Pitt-Hopkins-like syndrome (Zweier et al., J Med Genet 80: 994-1001, 2007).We present the first case report of a child in Iraq with Pitt-Hopkins-like syndrome that was referred to the Welfare Children’s Hospital/Medical City of Baghdad because of her intellectual disability.Case presentationThe patient was 4-year-old female child who presented with psychomotor delay and language impairment. She had frequent attacks of the respiratory tract and eye infections. Ophthalmologic examination revealed left-sided esotropia and severe myopia. Routine hematologic, serologic, and chemistry tests were within normal ranges. EEG revealed diffuse theta slowing and diffuse beta activity. The audiological test was normal. NCS and EMG showed normal results. Echo study, chest X-ray, and abdominal/pelvic ultrasound revealed normal findings. Brain MRI showed mild bilateral frontal-temporal atrophy. Whole-exome sequencing (WES) revealed a homozygous stop mutation in CNTNAP2 with a heterozygous state in both parents.ConclusionIntellectual disability may result from different types of abnormal cellular processes and with widening the use of molecular gene analysis in cases of intellectual disability, underdiagnosed cases of Pitt-Hopkins and Pitt-Hopkins-like syndromes may be uncovered.

Highlights

Pitt-Hopkins syndrome (PHS) is a rare cause of severe intellectual disability, seizures, language impairment, and peculiar facial dysmorphism
The syndrome is characterized by intellectual dysfunction, seizures, language impairment, postnatal growth retardation, and microcephaly
This syndrome is characterized by a particular breathing pattern that appears in mid-childhood and manifests as paroxysms of dyspnea followed by apnea and occasional cyanosis

Summary

Introduction

Pitt-Hopkins syndrome (PHS) is a rare cause of severe intellectual disability, seizures, language impairment, and peculiar facial dysmorphism. It is caused by a mutation in transcription factor 4 (TCF4). We present the first case report of a child in Iraq with Pitt-Hopkins-like syndrome that was referred to the Welfare Children’s Hospital/Medical City of Baghdad because of her intellectual disability. Case presentation: The patient was 4-year-old female child who presented with psychomotor delay and language impairment. She had frequent attacks of the respiratory tract and eye infections. Pitt-Hopkins syndrome (PHS) is a rare cause of severe intellectual disability first detected in 1978 in two patients [1]. Pitt-Hopkins syndrome is frequently misdiagnosed if not supported by genetic evidence [5]

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