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Heliyon Apr 2024gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister-Hall syndrome (PHS, MIM:...
BACKGROUND
gene mutations can result in various forms of polysyndactyly, such as Greig cephalopolysyndactyly syndrome (GCPS, MIM: #175700), Pallister-Hall syndrome (PHS, MIM: #146510), and isolated polydactyly (IPD, MIM: #174200, #174700). Reports on IPD-associated mutations are rare. In this study, a novel mutation was identified in a Chinese family with IPD.
RESULTS
We report a family with six members affected by IPD. The family members demonstrated several special phenotypes, including sex differences, abnormal finger joint development, and different polydactyly types. We identified a novel frameshift variant in the gene (NM_000168.6: c.1820_1821del, NP_000159.3: p.Tyr607Cysfs*9) by whole-exome sequencing. Further analysis suggested that this mutation was the cause of polydactyly in this family.
CONCLUSIONS
The discovery of this novel frameshift variant in our study further solidifies the relationship between IPD and and expands the previously established spectrum of mutations and associated phenotypes.
PubMed: 38571622
DOI: 10.1016/j.heliyon.2024.e28638 -
Frontiers in Nephrology 2023CAKUT is the leading cause of end-stage kidney disease in children and comprises a broad spectrum of phenotypic abnormalities in kidney and ureter development. Molecular... (Review)
Review
CAKUT is the leading cause of end-stage kidney disease in children and comprises a broad spectrum of phenotypic abnormalities in kidney and ureter development. Molecular mechanisms underlying the pathogenesis of CAKUT have been elucidated in genetic models, predominantly in the mouse, a paradigm for human renal development. Hedgehog (Hh) signaling is critical to normal embryogenesis, including kidney development. Hh signaling mediates the physiological development of the ureter and stroma and has adverse pathophysiological effects on the metanephric mesenchyme, ureteric, and nephrogenic lineages. Further, disruption of Hh signaling is causative of numerous human developmental disorders associated with renal malformation; Pallister-Hall Syndrome (PHS) is characterized by a diverse spectrum of malformations including CAKUT and caused by truncating variants in the middle-third of the Hh signaling effector GLI3. Here, we outline the roles of Hh signaling in regulating murine kidney development, and review human variants in Hh signaling genes in patients with renal malformation.
PubMed: 37675356
DOI: 10.3389/fneph.2023.1176347 -
Frontiers in Neurology 2023Hypothalamic hamartoma (HH) is a rare intracranial disease whose manifestations include gelastic seizures and precocious puberty. The diagnosis and treatment of HH have...
BACKGROUND
Hypothalamic hamartoma (HH) is a rare intracranial disease whose manifestations include gelastic seizures and precocious puberty. The diagnosis and treatment of HH have changed substantially over the past three decades as medical care has improved. Bibliometrics can reveal the evolution and development of a scientific field.
METHODS
Documents on HH were retrieved from the Web of Science Core Collection (WoSCC) database on September 8, 2022. The search terms were as follows: "hypothalamic hamartoma" or "hamartoma of the hypothalamus" or "hypothalamic hamartomas." The types of documents were restricted to articles, case reports, and reviews. VOSviewer, CiteSpace, and the R package "bibliometrix" were used for a bibliometric analysis.
RESULTS
A total of 667 independent documents on HH were obtained from the WoSCC database. The most common types of documents were articles ( = 498, 75%) and reviews ( = 103, 15%). The number of annual publications fluctuated but showed an upward trend overall, and the annual growth rate was 6.85%. The cumulative publication data indicated that the most influential journals in the HH field include , , , , and the . Kerrigan JF, Ng YT, Rekate HL, Regis J, and Kameyama S were among the most prominent authors in the field of HH, with numerous publications and citations. American research institutions, especially the Barrow Neurological Institute, occupied a pivotal position in HH research. Other countries and institutions were catching up and producing considerable research results. Research on HH has steadily switched its emphasis from Pallister-Hall syndrome (PHS) and precocious puberty to epilepsy and new diagnostic and therapeutic techniques, including Gamma Knife, laser ablation, and interstitial thermal therapy.
CONCLUSION
HH remains a special neurological disease with significant research prospects. The development of novel technologies, including MRI-guided laser-induced thermal therapy (MRg-LiTT) and stereotactic radiofrequency thermocoagulation (RF-TC), has enabled the efficient treatment of gelastic seizures in HH while minimizing the risks associated with craniotomies. Through bibliometric analysis, this study points out the direction for future HH research.
PubMed: 37416311
DOI: 10.3389/fneur.2023.1176459 -
Cureus Apr 2023Bifid epiglottis is a rare congenital laryngeal anomaly that is most commonly a syndromic rather than an isolated entity. It has been associated with specific...
Bifid epiglottis is a rare congenital laryngeal anomaly that is most commonly a syndromic rather than an isolated entity. It has been associated with specific syndromes, such as Pallister-Hall syndrome, Bardet-Biedl syndrome, and other related syndromes. Bardet-Biedl syndrome is a rare autosomal-recessive disorder characterized by hand and/or feet polydactyly, obesity, short stature, mental retardation, renal anomalies, and genital anomaly. Here we report a case involving a 25-year-old Saudi male patient who presented with hoarseness of voice since birth with no diurnal or diet association or other associated symptoms. On examination, he was noted to have craniofacial dysmorphism and polydactyly of the right hand and left foot. Fiberoptic nasopharyngolaryngoscopy (NPLS) revealed a laryngeal pedunculated rounded glottic mass and subglottic bulging with expiration and involuting with inspiration along with an abnormal-looking epiglottis having a separate cartilaginous framework with space in-between and bilateral mobile vocal cords. Computed tomography (CT) showed the vocal cord mass and a bifid epiglottis. Other investigations and labs were within normal range. The patient underwent vocal cord mass excision and soft tissue histopathology revealed a benign growth. On follow-up, the patient showed clinical improvement. In conclusion, this is a rare case of bifid epiglottis associated with Bardet-Biedl syndrome, which serves to highlight the significance of such anomalies in any syndromic patient presenting with airway symptoms. Our aim is to add more cases to the literature and to consider it as a differential diagnosis.
PubMed: 37214040
DOI: 10.7759/cureus.37849 -
Clinical Pediatric Endocrinology : Case... 2023Pallister-Hall syndrome (PHS) is defined as a group of characteristic manifestations caused by a monoallelic pathogenic variant. A two-month-old infant was referred to...
Pallister-Hall syndrome (PHS) is defined as a group of characteristic manifestations caused by a monoallelic pathogenic variant. A two-month-old infant was referred to our institution because of undetermined sex. The infant had atypical genitalia with postaxial polysyndactyly, a hypothalamic mass, and an imperforate anus. We identified a known pathogenic variant of the gene within one week and diagnosed the infant with PHS. The parents assigned the infant as male, considering the 46,XY karyotype, normal testosterone secretion, possible male identity, and the natural history of PHS. In infants with atypical genitalia and other malformations, such as polydactyly, a hypothalamic mass, or an imperforate anus, rapid testing may provide information for planning lifelong management, including sex assignment.
PubMed: 37020703
DOI: 10.1297/cpe.2022-0065 -
Clinical Case Reports Aug 2022Pallister-Hall syndrome (PHS) is a very rare genetic disorder. The diagnosis is usually suspected at the young age when a hypothalamic hamartoma is associated with...
Pallister-Hall syndrome (PHS) is a very rare genetic disorder. The diagnosis is usually suspected at the young age when a hypothalamic hamartoma is associated with polydactyly. Endocrine manifestations are mostly related to hypothalamic hamartoma and rarely reveal the disease. We report the case of an 18-year-old young man in whom the diagnosis of PHS was delayed until his hospitalization in the endocrinology department for acute adrenal insufficiency.
PubMed: 36017114
DOI: 10.1002/ccr3.6249 -
Pediatric Neurology Jun 2022GLI3 encodes a zinc finger transcription factor that plays a role in the sonic hedgehog pathway. Germline pathogenic GLI3 variants are associated with Greig...
BACKGROUND
GLI3 encodes a zinc finger transcription factor that plays a role in the sonic hedgehog pathway. Germline pathogenic GLI3 variants are associated with Greig cephalopolysyndactyly and Pallister-Hall syndromes, two syndromes involving brain malformation and polydactyly.
METHODS
We identified patients with pathogenic GLI3 variants and brain malformations in the absence of polydactyly or other skeletal malformation.
RESULTS
Two patients were identified. Patient #1 is a 4-year-old boy with hypotonia and global developmental delay. Brain MRI showed a focal cortical dysplasia, but he had no history of seizures. Genetic testing identified a de novo likely pathogenic GLI3 variant: c.4453A>T, p.Asn1485Tyr. Patient #2 is a 4-year-old boy with hypotonia, macrocephaly, and global developmental delay. His brain MRI showed partial agenesis of the corpus callosum, dilatation of the right lateral ventricle, and absent hippocampal commissure. Genetic testing identified a de novo pathogenic GLI3 variant: c.4236_4237del, p.Gln1414AspfsTer21. Neither patient had polydactyly or any apparent skeletal abnormality.
CONCLUSIONS
These patients widen the spectrum of clinical features that may be associated with GLI3 pathogenic variants to include hypotonia, focal cortical dysplasia, and other brain malformations, in the absence of apparent skeletal malformation. Further study is needed to determine if GLI3 pathogenic variants are a more common cause of focal cortical dysplasia or corpus callosum agenesis than presently recognized.
Topics: Brain; Child, Preschool; Hedgehog Proteins; Humans; Male; Malformations of Cortical Development; Muscle Hypotonia; Nerve Tissue Proteins; Phenotype; Polydactyly; Syndrome; Zinc Finger Protein Gli3
PubMed: 35436645
DOI: 10.1016/j.pediatrneurol.2022.03.005 -
BMC Neurology Mar 2022Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is... (Review)
Review
BACKGROUND
Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects.
CASE PRESENTATION
We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins.
DISCUSSION AND CONCLUSIONS
We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas' sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.
Topics: Hamartoma; Humans; Hypothalamic Diseases; Infant, Newborn; Neuroimaging; Pallister-Hall Syndrome; Twins, Monozygotic
PubMed: 35331151
DOI: 10.1186/s12883-022-02618-0 -
Cureus Jan 2022Pallister-Hall syndrome (PHS) is an extremely rare genetic disorder for which the diagnosis is often overlooked. The objective of this case report is to highlight how...
Pallister-Hall syndrome (PHS) is an extremely rare genetic disorder for which the diagnosis is often overlooked. The objective of this case report is to highlight how clinical features used in conjunction with brain MRI findings can lead to an expeditious diagnosis without the need for invasive measures or genetic test results. We present the case of a three-day-old infant delivered at 34 and 4/7 weeks gestation who presented with mild respiratory distress and bilious emesis in the setting of an uncomplicated gestational course and vaginal delivery with no known teratogen exposure. A diagnosis of Pallister-Hall syndrome was made on the basis of physical exam findings, hormonal abnormalities and the identification of a hypothalamic hamartoma on brain MRI. The patient underwent multiple procedures for diagnosis and management of PHS complications, including a diverting jejunostomy for a long-segment Hirschsprung's and a laryngoscopy which identified a bifid epiglottis. The patient tolerated the interventions and did not have seizures on admission. The MRI brain detection of a hypothalamic hamartoma led to an earlier diagnosis of Pallister-Hall syndrome and thus further screening and identification of complications associated with this disorder were performed before genetic analyses or brain biopsies were obtained. Given the unique MRI features of hypothalamic hamartomas, brain MRI can be a useful tool for making an early PHS diagnosis when taken with clinical features concerning possible PHS.
PubMed: 35251807
DOI: 10.7759/cureus.21735