[…] in heterozygosis, also present in the father. [elsevier.es]

Parent-Rated Questionnaires The results of parent-rated questionnaires are presented in Table 2. [cambridge.org]

In contrast to patients with Pitt-Hopkins syndrome, PTHSL1 patients present with normal or only mildly to moderately delayed motor milestones. [uniprot.org]

• Epilepsy

  A case series of 21 patients with PTHS and epilepsy found that the median age of seizure onset was two years and that focal and generalized epilepsies occurred with the same prevalence. [jtggjournal.com]

  Keywords: CNTNAP2; cortical dysplasia-focal epilepsy syndrome; developmental delay; epilepsy; intellectual disability; pediatrics; pitt Hopkins-like syndrome 1. © The Author(s) 2021. [pubmed.ncbi.nlm.nih.gov]

  This breathing anomaly shows no relation to epilepsy [2,3,4]. [jmhg.springeropen.com]

  An increase of the epilepsy was often noted during fever. [ojrd.biomedcentral.com]

  Rosenfeld et al. [2009] found 7 of 8 patients in their series with a missense mutation to have epilepsy, while other types of mutations were associated with epilepsy in only 16–18% of cases. [karger.com]

• Pain

  Measures such as the Face, Legs, Activity, Cry and Consolability (FLACC) behavioural pain assessment scale [78] and the Non-Communicating Children’s Pain Checklist (NCCPC [79]) have been utilised effectively to explore the relationship between pain and [jneurodevdisorders.biomedcentral.com]

  Other signs of PTHS include: Behavioral problems, such as hyperactivity or anxiety Constipation, reflux and other digestive issues Happy dispositions with lots of laughter High pain threshold Nonverbal (use of simple words or hand gestures to communicate [childrens.com]

  Most individuals have a high pain threshold. Additional symptoms can include excessive drooling (especially when younger), severe nearsightedness (myopia), crossed eyes (strabismus), and abnormal curving of the lens of the eye (astigmatism). [rarediseases.org]

• Tachypnea

  Rnx-deficient mice display an abnormal respiratory pattern, with alternating tachypnea and apnea [Shirasawa et al., 2000]. [karger.com]

• Constipation

  These children and adults may have impaired speech development, autistic behavior, breathing anomalies, constipation, and strabismus, resembling Pitt Hopkins syndrome. [pitthopkins.org]

  […] upper lip 0000219 Tricuspid regurgitation 0005180 Ventricular septal defect Hole in heart wall separating two lower heart chambers 0001629 Percent of people who have these symptoms is not available through HPO Autosomal recessive inheritance 0000007 Constipation [rarediseases.info.nih.gov]

  Other signs of PTHS include: Behavioral problems, such as hyperactivity or anxiety Constipation, reflux and other digestive issues Happy dispositions with lots of laughter High pain threshold Nonverbal (use of simple words or hand gestures to communicate [childrens.com]

  A frequent ailment is severe constipation, but only one patient had Hirschsprung disease [Peippo et al., 2006]. No hearing defects have been reported. [karger.com]

  Constipation is very common with Pitt-Hopkins and usually standard measures such as high fiber diets or laxatives are sufficient. [rarediseases.org]

• Vomiting

  Other signals picked up as first signs by parents were failure to thrive, gastrointestinal problems (such as reflux, feeding problems, vomiting, constipation), and other symptoms, such as cyanosis during crying, breathing problems, seizures and abnormal [ojrd.biomedcentral.com]

• Cyanosis

  These episodes can cause a lack of oxygen in the blood, leading to a bluish appearance of the skin or lips (cyanosis). In some cases, the lack of oxygen can cause loss of consciousness. [encyclopedia.pub]

  Hands and feet may be cold or bluish in appearance due to cyanosis. Causes Pitt-Hopkins syndrome is caused by an unexpected change (mutation) in the TCF4 gene. [rarediseases.org]

  Hyperventilation may occur and is sometimes followed by apnea and cyanosis. Constipation is common. Microcephaly and seizures may occur. Hypopigmented skin macules have occasionally been reported. [en.wikipedia.org]

  Nearly half of patients with PTHS have spells of abnormal breathing, including hyperventilation, which may be followed by apnea with rapid onset of cyanosis[1]. [jtggjournal.com]

• Small Hand

  Affected individuals may also have small hands and feet, a single crease across the palms of the hands, flat feet (pes planus), or unusually fleshy pads at the tips of the fingers and toes. [encyclopedia.pub]

  Examination showed a happy demeanor, microcephaly (head circumference is 45 cm), wide nasal bridge, and tip, narrow forehead, cupid-bow-shaped upper lip, wide mouth, full lips, and small hands. She is hyperactive with severe speech impairment. [jmhg.springeropen.com]

  The hand stereotypies have been described as repeated hand-to-mouth movements, hand clapping, flapping, wringing, swaying, or lateral movements, and they may be triggered by attempts to interact with the environment. [karger.com]

• Muscle Weakness

  Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. [ncbi.nlm.nih.gov]

• Macrocephaly

  A rare genetic epilepsy characterized by relatively large head circumference or macrocephaly, diminished or absent deep-tendon reflexes and mild gross motor delay in infancy, followed by intractable focal seizures with language regression, behavioral [ncbi.nlm.nih.gov]

• Strabismus

  These children and adults may have impaired speech development, autistic behavior, breathing anomalies, constipation, and strabismus, resembling Pitt Hopkins syndrome. [pitthopkins.org]

  In this case report, the proband is a seven year old female with PTHLS1, developmental delay, autism spectrum disorder, focal epilepsy, hypotonia, refractory errors, strabismus, and obstructive sleep apnea. [pubmed.ncbi.nlm.nih.gov]

  Other features of Pitt-Hopkins syndrome may include constipation and other gastrointestinal problems, an unusually small head (microcephaly), nearsightedness (myopia), eyes that do not look in the same direction (strabismus), short stature, and minor [encyclopedia.pub]

  Chronic constipation Infrequent bowel movements 0012450 Epileptic encephalopathy 0200134 Failure to thrive Faltering weight Weight faltering [ more ] 0001508 Hyperventilation Rapid breathing 0002883 Seizure 0001250 Sleep-wake cycle disturbance 0006979 Strabismus [rarediseases.info.nih.gov]

• Esotropia

  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. [x-mol.com]

  Ophthalmologic examination revealed left-sided esotropia and severe myopia. See Fig. 1. [jmhg.springeropen.com]

• High Nasal Root

  nasal root.[7] The facial features are characteristic and include:[9] Broad nasal bridge with bulbous tip Wide Mouth Cupid's bow philtrum Prominent Ears Flat feet Overriding toes Fetal Pads Short Stature Scoliosis Adults who have PTHS may have trouble [en.wikipedia.org]

• Ataxia

  Cerebellar ataxia MedGen UID: 849 •Concept ID: C0007758 • Disease or Syndrome Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. [ncbi.nlm.nih.gov]

  Floppiness or poor muscle control is a key sign, as well as poor coordination (ataxia). A child with PTHS may be late to roll over, sit up or grab for things. If they’re able to walk, they may be wobbly and need a walker or leg braces for support. [childrens.com]

  Additional symptoms that can occur include poor coordination (ataxia), repetitive nonfunctional hand movements, constipation, sleep disturbances, and severe nearsightedness (myopia). [rarediseases.org]

  Speech is often absent, and motor delays (independent ambulation after 5 years of age or not at all), ataxia, and motor incoordination occur in the majority of cases. [cambridge.org]

  Hypotonia and delays in motor development are also prevalent, most notably delayed or absent walking, impaired motor coordination and ataxia [6, 8]. [jneurodevdisorders.biomedcentral.com]

• High Pain Threshold

  Other signs of PTHS include: Behavioral problems, such as hyperactivity or anxiety Constipation, reflux and other digestive issues Happy dispositions with lots of laughter High pain threshold Nonverbal (use of simple words or hand gestures to communicate [childrens.com]

  Most individuals have a high pain threshold. Additional symptoms can include excessive drooling (especially when younger), severe nearsightedness (myopia), crossed eyes (strabismus), and abnormal curving of the lens of the eye (astigmatism). [rarediseases.org]

• Poor Coordination

  Floppiness or poor muscle control is a key sign, as well as poor coordination (ataxia). A child with PTHS may be late to roll over, sit up or grab for things. If they’re able to walk, they may be wobbly and need a walker or leg braces for support. [childrens.com]

  Additional symptoms that can occur include poor coordination (ataxia), repetitive nonfunctional hand movements, constipation, sleep disturbances, and severe nearsightedness (myopia). [rarediseases.org]

• Hyporeflexia

  Heartburn [ more ] 0002020 Gluten intolerance Gluten sensitivity 0012538 Hearing impairment Deafness Hearing defect [ more ] 0000365 High anterior hairline High frontal hairline 0009890 High-pitched cry 0025430 Hyperactivity More active than typical 0000752 Hyporeflexia [rarediseases.info.nih.gov]

  Hyporeflexia MedGen UID: 195967 •Concept ID: C0700078 • Finding Reduction of neurologic reflexes such as the knee-jerk reaction. [ncbi.nlm.nih.gov]

• Hyperreflexia

  Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. [ncbi.nlm.nih.gov]

Genetic workup is essential in identification and management guidance in these populations. [pubmed.ncbi.nlm.nih.gov]

Clinical Evaluations and Workup If the diagnosis is suspected by exam and history, molecular testing can be ordered. [rarediseases.org]

[…] and treatment of disorders of the gastrointestinal tract), an ophthalmologist (a physician who specializes in the diagnosis and treatment of disorders of the eye), a pulmonologist (a physician who specializes in the diagnosis and treatment of disorders [rarediseases.org]

The advantage of gene therapy over pharmacological treatment is that it would solve the problem at its source. However, the search for new drugs is also promising,” Papes said. [agencia.fapesp.br]

Mowat–Wilson syndrome is seen in early infancy and is characterized by distinctive facial abnormalities.[12] Treatment[edit] Currently there is no specific treatment for this condition. It is based on symptomatology. [en.wikipedia.org]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice. [uniprot.org]

Thus, this case demonstrates the importance of having a treatment team that includes a neuropsychologist to improve quality of life for individuals with PTHS and their families. [cambridge.org]

Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis. Infants with Pitt-Hopkins syndrome may have diminished muscle tone (hypotonia) and appear abnormally “floppy.” [rarediseases.org]

PMID: 25495786 Prognosis Veersema TJ, van Schooneveld MMJ, Ferrier CH, van Eijsden P, Gosselaar PH, van Rijen PC, Spliet WGM, Mühlebner A, Aronica E, Braun KPJ Epilepsy Behav 2019 May;94:209-215. Epub 2019 Apr 8 doi: 10.1016/j.yebeh.2019.03.009. [ncbi.nlm.nih.gov]

Larger studies are needed to confirm this observation, which may guide the prognosis and diagnosis of epilepsy in PTHS. PTHS patients have three types of paroxysmal events: epileptic seizures, abnormal breathing spells, and motor stereotypies. [jtggjournal.com]

PTHS is likely underdiagnosed, and clinicians should use comprehensive genetic testing methods with patients with developmental delays to investigate the possible presence of an underlying genetic etiology. [cambridge.org]

Point mutations in ZBTB18 and HNRNPU were implicated etiologies. [jmhg.springeropen.com]

Etiology Veersema TJ, van Schooneveld MMJ, Ferrier CH, van Eijsden P, Gosselaar PH, van Rijen PC, Spliet WGM, Mühlebner A, Aronica E, Braun KPJ Epilepsy Behav 2019 May;94:209-215. Epub 2019 Apr 8 doi: 10.1016/j.yebeh.2019.03.009. [ncbi.nlm.nih.gov]

Altogether 78 PTHS patients with abnormalities of the TCF4 gene have been published since 2007 when the etiology of PTHS was revealed. [karger.com]

Epidemiology No population-based prevalence or incidence figures for PTHS are available at present. Until 2007, PTHS was rarely reported, but increasing numbers of patients have been published since molecular testing became available. [karger.com]

Common Pathophysiology in Multiple Mouse Models of Pitt-Hopkins Syndrome. J. Neurosci. 2018, 38, 918–936. [Google Scholar] [CrossRef] Li, H.; Zhu, Y.; Morozov, Y.M.; Chen, X.; Page, S.C.; Rannals, M.D.; Maher, B.J.; Rakic, P. [mdpi.com]

Physiotherapy to prevent contractures is important as the patients’ own ability to move independently is very limited. Myopia is frequent in PTHS patients and might be underdiagnosed. [karger.com]