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Pallister-Hall Syndrome

PHS

Pallister-Hall syndrome is a very rare genetic disorder characterized by polydactyly, nail dysplasia, a bifid epiglottis, and hypothalamic hamartomas producing specific forms of epilepsy. First signs are seen at birth. The prognosis depends on the severity of the disease, ranging from mild to severe and life-threatening. The diagnosis rests on a thorough clinical assessment, followed by imaging studies and molecular genetic testing.


Presentation

Pallister-Hall syndrome, firstly described 40 years ago, is an extremely rare genetic disorder [1] [2] [3] [4]. The pathogenesis stems from mutations in the GLI3 gene on chromosome 7p13, which is involved in the sonic hedgehog pathway, a key signaling process of cell maturation [1] [3] [5]. So far, the majority of cases have been described as familial with an autosomal dominant pattern of inheritance [1] [3]. The nature of the disorder causes signs and symptoms to be evident from birth. Several key features comprise Pallister-Hall syndrome [1] [2] [3] [4] [5] [6]:

  • Polydactyly - The presence of additional fingers arising from the ulnar/fibular parts of the limbs is a crucial clinical finding in this patient population, often accompanied by dysplasia of the nails [1].
  • Hypothalamic hamartoma - Hamartomas can be quite large (up to several centimeters in length) and produce seizures. The term "gelastic epilepsy" is used to describe a specific type of a partial complex seizure that presents with clonic movements of the diaphragm and chest and mimic laughing [1]. Other neurological deficits, growth hormone deficiency, or even precocious puberty has been attributed to hamartomas, but many patients are surprisingly asymptomatic [1] [6]. In fact, surgical treatment is often contraindicated due to consequent hypopituitarism and several other complications. In rare patients who develop Pallister-Hall syndrome in a sporadic fashion, deficiency of cortisol might be encountered [1].
  • Bifid epiglottis - In the majority of cases, this anatomical abnormality is asymptomatic, but severe derangements lead to dangerous airway obstruction and death without early treatment [1] [3].

Additional signs and symptoms include renal malformation (hypoplasia, agenesis, ectopic kidneys, or development of cysts), genitourinary changes (imperforate anus, hydrometrocolpos), and skeletal changes such as short limbs [1] [3] [6].

Short Stature
  • We conclude that children with Pallister-Hall syndrome and short stature be evaluated carefully for spontaneous somatotropic function and, if necessary, treated with growth hormone.[ncbi.nlm.nih.gov]
  • Growth hormone (GH) deficiency follows; in children, this causes short stature, delayed growth, and delayed puberty.[checkorphan.org]
  • Idiopathic short stature (ISS) Idiopathic short stature is characterized by significant short stature ( rd percentile for height will be found to be growth hormone deficient or have mutations involving growth hormone releasing hormone (GHRH), GH, IGF-[hormones.gr]
  • stature, and intellectual disabilities) 759.89 Rud's (mental deficiency, epilepsy, and infantilism) 759.89 Russell (-Silver) (congenital hemihypertrophy and short stature) 759.89 Seckel's 759.89 sick Silver's (congenital hemihypertrophy and short stature[icd9data.com]
  • Hall specialized in the genetic factors that affect lack of children’s growth, including the mechanism of neural tube defects, the genetics of short stature and the genetics of connective tissue disorders such as arthrogryposis, dwarfism, and monozygotic[cdnmedhall.org]
Progressive Mental Retardation
  • The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures.[ncbi.nlm.nih.gov]
Kidney Failure
  • Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with gastrointestinal obstruction. Iodine is considered to be safe in recommended doses for pregnant or breastfeeding women.[livingnaturallyonline.com]

Workup

Because of the very rare occurrence of Pallister-Hall syndrome in general practice, the diagnosis may be difficult to attain. For this reason, an early clinical workup is critical in order to recognize the key elements of this disorder. Physicians should first obtain a detailed patient history that will cover the onset of symptoms and their progression. A detailed family history must not be overlooked because of the autosomal dominant pattern of inheritance. After history taking, the physical examination can discover polydactyly and additional anatomical changes, but in order to solidify the diagnosis and obtain additional evidence toward Pallister-Hall syndrome, imaging studies are necessary. The cardinal feature, hypothalamic hamartoma, is best seen through magnetic resonance imaging (MRI), as neither computed tomography (CT) nor cranial ultrasonography are able to detect it [1]. A non-calcified and non-enhancing mass, usually located behind the optic chiasm and on the third ventricle floor, exhibits an isointense signal on T1 and T2-weighted studies [1] [3]. Molecular genetic techniques, which are able to detect the mutated GLI3 gene on chromosome 7, serve as the definitive method for diagnosing Pallister-Hall syndrome [1].

Hypsarrhythmia
  • We describe a male infant with Pallister-Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [(18)F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated[ncbi.nlm.nih.gov]

Treatment

  • Bifid epiglottis - In the majority of cases, this anatomical abnormality is asymptomatic, but severe derangements lead to dangerous airway obstruction and death without early treatment.[symptoma.com]
  • Standard treatment of anal atresia or stenosis; symptomatic treatment of seizures; elective repair of polydactyly; developmental intervention or special education for developmental delays.[ncbi.nlm.nih.gov]
  • Make the best clinical decisions with an enhanced emphasis on evidence-based practice and expert opinions on treatment strategies. Zero in on the most relevant and useful references with the aid of a more focused, concise bibliography.[books.google.com]
  • The webbing between some fingers or toes may also be joined together Treatment of the condition is based on the severity and type of symptoms presented Prognosis is dependent on many factors, including the signs and symptoms and access to early treatment[dovemed.com]

Prognosis

  • This patient's phenotype was complex with unusual gastrointestinal features ultimately leading to a unfavorable prognosis and outcome, highlighting the range of clinical severity in patients with Pallister-Hall syndrome.[ncbi.nlm.nih.gov]
  • Prognosis Because of the broad range and severity of Pallister-Hall signs and symptoms, the prognosis varies widely from case to case.[encyclopedia.com]
  • Prognosis - Pallister-Hall syndrome Because of the broad range and severity of Pallister-Hall signs and symptoms, the prognosis varies widely from case to case.[checkorphan.org]
  • Prognosis The prognosis for an individual with PHS and no known family history of PHS is based on the malformations present in the individual.[atlasgeneticsoncology.org]
  • The prognosis depends on the severity of the disease, ranging from mild to severe and life-threatening. The diagnosis rests on a thorough clinical assessment, followed by imaging studies and molecular genetic testing.[symptoma.com]

Etiology

  • The known genetic parallels between these conditions is discussed briefly in terms of etiology.[ncbi.nlm.nih.gov]
  • We aim to use the power of modern molecular genetics and clinical research to delineate the range of severity, natural history, molecular etiology, and pathophysiology of a number of congenital anomaly syndromes.[clinicaltrials.gov]
  • The original reference is provided for historical interest, and review articles are included to show recent advances in etiology and treatment.[books.google.com]
  • […] polydactyly midline facial capillary hemangioma nail dysplasia cerebral anomalies holoprosencephaly hypothalamic hamartoblastoma pituitary aplasia or dysplasia endocrine anomalies pan hypopituitarism adrenal gland hypoplasia thyroid dysplasia/aplasia Etiology[humpath.com]
  • (Etiology) Pallister-Hall Syndrome is inherited as an autosomal dominant condition An error in gene (GLI3 gene) mutation, leading to the defective production of a protein by the body causes PHS.[dovemed.com]

Epidemiology

  • These include PhD programs in Epidemiology and Health Services Research, Master's programs in Public Health, Epidemiology, Clinical Investigation, and Health Services Research, and 6 Advanced Certificates in Epidemiology, Health Services Research, Biomedical[urmc.rochester.edu]
  • The protocol for data collection included epidemiological aspects, as well as immediate and late complications. RESULTS: ninety-six patients were enrolled.[ncbi.nlm.nih.gov]
  • Richter 1955 first successful repair by Pettersson 1979 first endoscopic repair by Yamashita 1987 Tucker described submucouscleft 1989 Benjamin and Inglisdeveloped classification system most widely used today 2006 Sandumodified classification system EPIDEMIOLOGY[laryngeal-cleft.com]
  • Epidemiology, genetics, and syndromology, Teratology, 40, 3, (211-235), (2005). John B. Moeschler, Barbara R. Pober, Lewis B. Holmes and John M.[doi.org]
  • Epidemiology Frequency United States Potter syndrome is mostly associated with obstruction of the urinary tract or severe bilateral renal hypoplasia.[emedicine.medscape.com]
Sex distribution
Age distribution

Pathophysiology

  • We aim to use the power of modern molecular genetics and clinical research to delineate the range of severity, natural history, molecular etiology, and pathophysiology of a number of congenital anomaly syndromes.[clinicaltrials.gov]
  • Pathophysiology Prior to 16 weeks' gestations, the amount of amniotic fluid is dependent on the transmembrane flow. After that, fetal urine production is the predominant mechanism that determines the amniotic fluid volume.[emedicine.medscape.com]
  • Kazunori Arita, Hiroshi Tokimura, Ryosuke Hanaya, Sei Sugata, Tomohide Akimitsu, Koji Iida, Kazuhiko Sugiyama and Kaoru Kurisu, Hypothalamic Hamartoma: Pathophysiology and Treatment( New Therapies in Pediatric Neurosurgery), Japanese Journal of Neurosurgery[doi.org]

Prevention

  • This landmark study was begun in the fall of 1982 to test the benefits and risks of aspirin and beta carotene in the primary prevention of cardiovascular disease and cancer.[phs.bwh.harvard.edu]
  • Drug checking is an emerging harm reduction strategy that may help prevent overdose deaths.[phs.ca]
  • […] abnormalities - the pituitary gland produces a number of hormones (chemical messages) polydactyly (extra digits) and syndactyly (webbing between digits) small/unusual growing nails bifid epiglottis - a split in a leaflet of tissue at the back of the throat that prevents[contact.org.uk]
  • Currently, there are no specific methods or guidelines to prevent Pallister-Hall Syndrome genetic condition Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy)[dovemed.com]
  • ., finger nails and toe nails that are flaky and poorly grown) Airway defects that affect the epiglottis, which is the thin membrane structure located at the back of the tongue and which serves to prevent food and liquids from entering the wind pipe Inperforated[brighthub.com]

References

Article

  1. Biesecker LG. Pallister-Hall Syndrome. 2000 May 25 [Updated 2017 May 18]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  2. Azzam A, Lerner DM, Peters KF, Wiggs E, Rosenstein DL, Biesecker LG. Psychiatric and neuropsychological characterization of Pallister-Hall syndrome. Clin Genet. 2005;67(1):87-92.
  3. Kuo JS, Casey SO, Thompson L, Truwit CL. Pallister-Hall syndrome: clinical and MR features. AJNR Am J Neuroradiol. 1999;20(10):1839-1841.
  4. Biesecker LG, Graham JM. Pallister-Hall syndrome. J Med Genet. 1996;33(7):585-589.
  5. Boudreau EA, Liow K, Frattali CM, et al. Hypothalamic hamartomas and seizures: distinct natural history of isolated and Pallister-Hall syndrome cases. Epilepsia. 2005;46:42-47.
  6. Dericioglu N, Saygi S, Akalan N. Transcallosal endoscopic resection of hypothalamic hamartoma in a case with Pallister-Hall syndrome. Epileptic Disord. 2011;13(2):209-213.

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Last updated: 2019-06-28 10:29