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User:RiShebaB13/Pitt–Hopkins syndrome

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Pitt–Hopkins syndrome

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Pitt–Hopkins syndrome (PTHS) is a rare genetic disorder characterized by developmental delay, moderate to severe intellectual disability,[1] epilepsy, distinctive facial features, and possible intermittent hyperventilation followed by apnea.[2] Pitt–Hopkins syndrome can be marked by intellectual disabilities as well as problems with socializing.[3] Epilepsy (recurrent seizures)often occurs in Pitt-Hopkins.[1] Delays in speech are common, and individuals with Pitt-Hopkins are often non-verbal.[4] Pitt-Hopkins is part of the clinical spectrum of Rett-like syndromes.[5] Pitt-Hopkins syndrome is clinically similar to Angelman syndrome, Rett syndrome, and Mowat-Wilson syndrome, and ATR-X syndrome.[6]

As more is learned about Pitt–Hopkins, the developmental spectrum of the disorder is widening, and can also include difficulties with anxiety, autism,[7] ADHD, and sensory disorders. It is associated with an abnormality within chromosome 18 which causes insufficient expression of the TCF4 gene.[8] Those with PTHS have reported high rates of self-injury and aggressive behaviors usually related to autism and their sensory disorders.[3]

PTHS has traditionally been associated with severe cognitive impairment, however true intelligence is difficult to measure given motor and speech difficulties. Thanks to augmentative communication and more progressive therapies, many individuals can achieve much more than initially thought. It has become clearer that there is a wider range of cognitive abilities in Pitt–Hopkins than reported in much of the scientific literature. No cure is known for Pitt-Hopkins syndrome, but it is possible to treat associated symptoms.[6] Researchers have developed cell and rodent models to test therapies for Pitt–Hopkins.[9]

PTHS is estimated to occur in 1:11,000 to 1:41,000 people.[10]

Signs and symptoms

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PTHS can be seen as early as childhood.[11]

The earliest signs in infants is the lower face and the high nasal root.[10]

The facial features are characteristic and include:[12]

  • Broad nasal bridge with bulbous tip
  • Wide mouth
  • Cupid's bow philtrum
  • Prominent ears
  • Thin eyebrows
  • Flat feet
  • Overriding toes
  • Fetal pads
  • Short stature
  • Scoliosis
 

Adults who have PTHS may have trouble with their speech.[11] Craniofacial features, which are important when diagnosing PTHS, become more visible as the person gets older.[10]

Children with Pitt-Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. However, they can also experience anxiety and behavioral problems.[13]

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 brain abnormalities [14]

PTHS is characterized by developmental delay, possible breathing problems of episodic hyperventilation and/or breath-holding while awake, recurrent seizures/epilepsy, gastrointestinal issues, and distinctive facial features. Stereotypic movements, particularly of the arms, wrists and fingers are almost universal. Flat feet, overriding toes, fetal pads, are also common.[12] Short stature and scoliosis occur frequently.[12] Hypotonia is common (75%), as is an unsteady gait. Other features include a single (simian) palmar crease, long, slender fingers, flat feet and cryptorchidism (in males). The presence of "fetal finger pads" is common.

Hyperventilation may occur and is sometimes followed by apnea and cyanosis. Individuals with Pitt-Hopkins syndrome have episodes of heavy breathing. Constipation is common. Microcephaly and seizures may occur. Hypopigmented skin macules have occasionally been reported. Adults who have PTHS may have trouble with their speech.[11] Craniofacial features, which are important when diagnosing PTHS, become more visible as the person gets older.[10]

Individuals with Pitt–Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling and laughter.[citation needed]

Gastrointestinal

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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.[15]

Neurological

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Epilepsy is not uncommon in Pitt-Hopkins and is reported in 37%-50% of cases. The onset of seizures can occur in infants or throughout adulthood. A variety of seizures can occur. Electroencephalographic (EEG) patterns can be typical or atypical, depending on the individual.[15]

Magnetic resonance imaging (MRI) reveals that deviations in the brain may occur in individuals with Pitt-Hopkins. These can include a small corpus callosum, wide ventricles, and deviations in the posterior fossa. Many individuals with Pitt Hopkins can also have typical brain structures.[15]

Musculoskeletal

Minor hand and foot anomalies such as slender or small hands and feet, broad fingertips, clinodactyly, tapered fingers, transverse palmar crease, flat feet with hindfoot valgus deformity, overriding toes, and short metatarsals have been reported. Absent flexion creases of the thumbs may occur with thumb ankylosis. In one individual an absent thumb tendon was found during surgery [Authors, personal observation]. [16]

Diagnosis

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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.[11]

Zollino and colleagues defined diagnostic criteria based on characteristic features found in 75% of cases genetically confirmed for PTHS, termed cardinal features. If a person shows 9 cardinal features, they are classified as having PTHS.[15]

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. [15]

Half of the individuals with PTHS are reported to have seizures, starting from childhood to the late teens.[10]

Around 50% of those affected show abnormalities on brain imaging. These include a hypoplastic corpus callosum with a missing rostrum and posterior part of the splenium, with bulbous caudate nuclei bulging towards the frontal horns.[citation needed]

Electroencephalograms show an excess of slow components.[citation needed]

According to the clinical diagnosis. PTHS is in the same group as Pervasive Developmental Disorders.[17]

When a patient is suspected of having PTHS, genetic tests looking at the TCF4 gene are typically done.[10] Some argue for a genetic test to occur first, followed by a clinical assessment.[6]

Differential diagnosis

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PTHS is symptomatically similar to Angelman syndrome, Rett syndrome and Mowat–Wilson syndrome.[18]

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.[18]

Treatment

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Currently 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.[17] Comorbidities may also be treated. [6]

Care from a medical team including neurologists, ophthalmologists, pulmonologists, and gastroenterologists may be utilized. [6]

Recommendations for developmental delay and intellectual disability in the U.S. (may differ depending on country):[10]

  • 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.

References

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Instructor Feedback:

Risheba Brown: I see where you added a symptom above regarding alterations in breathing pattern. I would recommend that you integrate this as a bullet underneath the symptoms. It may warrant a statement, but that depends on the prevalence of this symptom. Be sure to include an appropriate citation. I would encourage you to review the final assignment rubric so you are aware of the areas I will be evaluating for the final submission. I would ask you to use underlining on your future edits. This will allow me to distinguish your contributions more easily from Anna's in the sandbox.

Anna Harden: Good work on your contributions thus far! I have integrated my suggested edits above with yours. Double check the integration of your citations. I believe the format for Wikipedia should look more like citation #3 where the author and title are visible. I also noted where the same DOI is listed for multiple numbered citations. You will want to clean this up (i.e., you cite the article one time and the number aligns to that one citation each time you use it in text).

The TCF4 gene can be affected without changing the phenotype to that of Pitt-Hopkins. [19] I would recommend revising this statement. I understand you what you are trying to say, essentially that the TCF4 gene can experience mutations or alterations that don't result in Pitt-Hopkins. This needs to be clearer.

Response to Peer-Reviews for Anna Harden:

The only peer-review that suggests changes to my article is the one by Kiara44D. I will post a summary of what Kiara wrote below along with my response. Kiara, thank you for your detailed feedback. See my responses below.

Retitle subheadings to Intro, Clinical Features, Genetic Basis, Treatment Options, and Conclusion for clarity. While I like the titles you provided, I believe the ones listed currently are still clear, and I would prefer not to change them because I do not have a good reason to justify changing what the other authors of the article have worked on.

Give specific examples ways Pitt-Hopkins is similar to other disorders. The other authors have provided this information under Differential Diagnosis.

Expand upon anxiety, autism, ADHD, sensory disorders. I think this would be too much detail for the lead section and is outside the scope of my research as of now. I will keep an eye out for this information, however, and add something if it seems relevant.

Add more about current treatment and management strategies. This is a good point. I will look into this.

Prevalence: Liz - I am finding different numbers depending upon the source. I am unsure how to account for this. I do believe the number 1:11,000 to 1:41,000 people is probably dated, however. Any suggestions on how to get a more accurate number?


Response to Peer Reviews for Ri'Sheba Brown:

User Maria.arriaga22 suggested changing the wording of the draft because there are sections that look similar to how the original current version of the article is. I think these changes will be made as we progress through making edits before the final draft of the article. Most peer-reviews were based on Anna's contributions as it appears that she has contributed more to the article than I have. I will admit that I am slightly confused on this portion of the Wiki assignments, and it is especially confusing since I share this sandbox with another student.

  1. ^ a b Sweetser, David A.; Elsharkawi, Ibrahim; Yonker, Lael; Steeves, Marcie; Parkin, Kimberly; Thibert, Ronald (2018-04-12), "Pitt-Hopkins Syndrome", GeneReviews® [Internet], University of Washington, Seattle, PMID 22934316, retrieved 2024-07-06
  2. ^ Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, et al. (May 2007). "Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome)". American Journal of Human Genetics. 80 (5): 994–1001. doi:10.1086/515583. PMC 1852727. PMID 17436255.
  3. ^ a b Watkins A, Bissell S, Moss J, Oliver C, Clayton-Smith J, Haye L, et al. (October 2019). "Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes". Journal of Neurodevelopmental Disorders. 11 (1): 24. doi:10.1186/s11689-019-9282-0. PMC 6778364. PMID 31586495.
  4. ^ Dean, Laura (2018-08-01), "Pitt-Hopkins Syndrome", Medical Genetics Summaries [Internet], National Center for Biotechnology Information (US), PMID 28520343, retrieved 2024-07-06
  5. ^ Whalen S, Héron D, Gaillon T, Moldovan O, Rossi M, Devillard F, et al. (January 2012). "Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum". Human Mutation. 33 (1): 64–72. doi:10.1002/humu.21639. PMID 22045651. S2CID 9559486.
  6. ^ a b c d e Goodspeed, Kimberly; Newsom, Cassandra; Morris, Mary Ann; Powell, Craig; Evans, Patricia; Golla, Sailaja (2018-01-10). "Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series". Journal of Child Neurology. 33 (3): 233–244. doi:10.1177/0883073817750490. ISSN 0883-0738. PMC 5922265. PMID 29318938.{{cite journal}}: CS1 maint: PMC format (link)
  7. ^ "Pitt-Hopkins syndrome may point the way to autism treatments". Daniel R. Weinberger. May 2019.
  8. ^ "Pitt-Hopkins". National Center for Biotechnology Information. Retrieved 2009-12-08.
  9. ^ "A drug for autism? Potential treatment for Pitt-Hopkins syndrome offers clues; PTHS". The Conversation. 26 April 2019. Retrieved 2019-07-10.
  10. ^ a b c d e f g Sweetser DA, Elsharkawi I, Yonker L, Steeves M, Parkin K, Thibert R (1993). "Pitt-Hopkins Syndrome". In MP, Ardinger HH, Pagon RA, Wallace SE (eds.). GeneReviews. University of Washington, Seattle. PMID 22934316. Cite error: The named reference "Sweetser_1993" was defined multiple times with different content (see the help page).
  11. ^ a b c d Dean L (2012). "Pitt-Hopkins Syndrome". In Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 28520343. Bookshelf ID: NBK66129.
  12. ^ a b c "Pitt-Hopkins Syndrome". Definitions. Qeios. 2020-02-02. doi:10.32388/nb53oy. S2CID 161843893. Retrieved 2022-10-16.
  13. ^ "Pitt-Hopkins syndrome", Definitions, Qeios, 2020-02-10, retrieved 2024-07-26
  14. ^ "Pitt-Hopkins syndrome", Definitions, Qeios, 2020-02-10, retrieved 2024-07-26
  15. ^ a b c d e Zollino, Marcella; Zweier, Christiane; Van Balkom, Ingrid D.; Sweetser, David A.; Alaimo, Joseph; Bijlsma, Emilia K.; Cody, Jannine; Elsea, Sarah H.; Giurgea, Irina; Macchiaiolo, Marina; Smigiel, Robert; Thibert, Ronald L.; Benoist, Ingrid; Clayton‐Smith, Jill; De Winter, Channa F. (2019-02-18). "Diagnosis and management in Pitt‐Hopkins syndrome: First international consensus statement". Clinical Genetics. 95 (4): 462–478. doi:10.1111/cge.13506. ISSN 0009-9163.
  16. ^ Sweetser, David A.; Elsharkawi, Ibrahim; Yonker, Lael; Steeves, Marcie; Parkin, Kimberly; Thibert, Ronald (1993), Adam, Margaret P.; Feldman, Jerry; Mirzaa, Ghayda M.; Pagon, Roberta A. (eds.), "Pitt-Hopkins Syndrome", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID 22934316, retrieved 2024-07-26
  17. ^ a b Sweatt JD (May 2013). "Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription". Experimental & Molecular Medicine. 45 (5): e21. doi:10.1038/emm.2013.32. PMC 3674405. PMID 23640545.
  18. ^ a b Cite error: The named reference Marangi_2015 was invoked but never defined (see the help page).
  19. ^ Zollino, Marcella; Zweier, Christiane; Van Balkom, Ingrid D.; Sweetser, David A.; Alaimo, Joseph; Bijlsma, Emilia K.; Cody, Jannine; Elsea, Sarah H.; Giurgea, Irina; Macchiaiolo, Marina; Smigiel, Robert; Thibert, Ronald L.; Benoist, Ingrid; Clayton‐Smith, Jill; De Winter, Channa F. (2019-02-18). "Diagnosis and management in Pitt‐Hopkins syndrome: First international consensus statement". Clinical Genetics. 95 (4): 462–478. doi:10.1111/cge.13506. ISSN 0009-9163.
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