Phenotypic and Molecular Heterogeneity in Mandibulofacial Dysostoses: A Case Series From India

2021 ◽  
pp. 105566562110500
Author(s):  
Rathika D. Shenoy ◽  
Vikram Shetty ◽  
Annelies Dheedene ◽  
Björn Menten ◽  
Dechamma Pandyanda Nanjappa ◽  
...  
Keyword(s):  
Outcome Measure ◽  
Collaborative Study ◽  
Case Series ◽  
Lower Eyelid ◽  
Treacher Collins Syndrome ◽  
Molecular Heterogeneity ◽  
Term Care ◽  
Aural Atresia ◽  
Pathogenic Variants ◽  
Mandibulofacial Dysostosis

Objective Facial dysostosis is a group of rare craniofacial congenital disabilities requiring multidisciplinary long-term care. This report presents the phenotypic and genotypic information from South India. Design The study is a case series. Setting This was an international collaborative study involving a tertiary craniofacial clinic and medical genetics unit. Patients, Participants The participants were 9 families with 17 affected individuals of facial dysostosis. Intervention Exome analysis focused on known genes associated with acrofacial and mandibulofacial syndromes. Main Outcome Measure The outcome measure was to report phenotyptic and genetic heterogeneity in affected individuals. Results A Tessier cleft was seen in 7 (41%), lower eyelid coloboma in 12 (65%), ear anomalies in 10 (59%), uniolateral or bilateral aural atresia in 4 (24%), and deafness in 6 (35%). The facial gestalt of Treacher Collins syndrome (TCS) showed extensive phenotypic variations. Pathogenic variants in TCOF1 (Treacher Collins syndrome) were seen in six families, POLR1A (acrofacial dysostosis, Cincinnati type) and EFTUD2 (mandibulofacial dysostosis with microcephaly) in one each. One family (11.1%) had no detectable variation. Five out of six probands with Treacher Collins syndrome had other affected family members (83.3%), including a non-penetrant mother, identified after sequencing. Conclusion Our report illustrates the molecular heterogeneity of mandibulofacial dysostosis in India.

scholarly journals Tail flap for eyelid reconstruction: An alternative to the Tenzel flap

2021 ◽  
pp. 21-28
Author(s):  
Golam Haider ◽  
Syeed Mehbub UI Kadir ◽  
Mukti Rani Mitra ◽  
Tanjila Hossain
Keyword(s):  
Reconstructive Surgery ◽  
Case Series ◽  
Lower Eyelid ◽  
Treacher Collins Syndrome ◽  
Juvenile Xanthogranuloma ◽  
Upper Eyelid ◽  
Eyelid Reconstruction ◽  
Triangular Flap ◽  
Case Series Study ◽  
Upper Lid

Purpose: To describe a technique of eyelid reconstruction with the tail flap method and also to evaluate the post-surgical outcome in a group of patients. Methods: This was a prospective case series study on nine patients who had undergone an eyelid reconstruction with the tail flap method. The study had been conducted from July 2014 to July 2019. The follow-up continued for six months to one year. Results: A total of nine patients with ten eyelid defects, 2 (22%) patients had unilateral eyelid coloboma, 1 (11%) had lower lid defect associated with Treacher-Collins syndrome,1 (11%)with bilateral upper eyelid coloboma, only one eyelid undergone lid reconstructive surgery associated with craniofacial anomalies,1 (11%) with Juvenile xanthogranuloma of the left upper eyelid,1(11%) with Basal cell carcinoma in the right upper lid, 3(34%) with Meibomian gland carcinoma 2 in lower eyelid and 1 in upper lid undergone lid reconstructive surgery with triangular flap. Among nine patients, a total of ten eyelid defects were repaired with the triangular flap technique, 5 (50%) in the upper eyelid and 5 (50%) in the lower eyelid. The eyelid defects were completely repaired with tail flap in all patients. All patients were evaluated preoperatively and postoperatively. The cosmetic outcomes of surgical intervention were excellent in 5(50%) cases, good in 3(30%) cases, fair enough in 2(20%) cases. Conclusions: Tail flap is an alternative surgical method to the well-established Tenzel flap in eyelid reconstruction. Keywords: Tail Flap; Tenzel Flap; Eyelid Defect; Lid reconstruction

S153 – Radiological Balloon Dilatation of Neo-Pharyngeal Strictures

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P127-P128
Author(s):  
Robert L Harris ◽  
Grundy Alan ◽  
Tunde A Odutoye
Keyword(s):  
Total Laryngectomy ◽  
Balloon Dilatation ◽  
Malignant Disease ◽  
Outcome Measure ◽  
Tertiary Care ◽  
Case Series ◽  
Stent Insertion ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Main Outcome Measure

Objectives Radiological balloon dilatation of lower oesophageal strictures is common practice. Other than some early reports from our own centre, there is little published regarding radiological dilatation of pharyngeal and upper oesophageal strictures and less still on radiological balloon dilatation of post-total laryngectomy and pharyngolaryngectomy neo-pharyngeal strictures. Standard practise is bouginage under general anaesthaesia. The objective of this study is to assess the efficacy of radiological balloon dilatation for the treatment of dysphagia secondary to neopharyngeal strictures in patients who have undergone laryngectomy. Methods A tertiary care centre case series of 20 consecutive patients (17 males and 3 females aged 40 to 84) with pharyngeal stricture and dysphagia post-total laryngectomy or pharyngolaryngectomy who underwent balloon dilatation of the stricture under radiological guidance. Maintenance of swallowing was the main outcome measure. Results 5 patients gained relief of their dysphagia with 1 balloon dilatation only. 9 patients required more than 1 dilatation to maintain swallowing. 2 patients had balloon dilatation procedures and stent insertion for palliative relief of dysphagia from known recurrent malignant disease. 3 patients failed to maintain swallowing with repeat dilatations. No patients suffered any significant complications such as perforation. Conclusions Balloon dilatation is minimally invasive and less traumatic than rigid pharyngoscopy with bouginage dilatation. It is well tolerated. It may be repeated frequently and can successfully relieve strictures of the pharynx in patients who have undergone total laryngectomy or pharyngolaryngectomy.

Psychotic disorders in young adults with perinatally acquired HIV: a UK case series

2020 ◽  
pp. 1-7
Author(s):  
I. Mallik ◽  
T. Pasvol ◽  
G. Frize ◽  
S. Ayres ◽  
A. Barrera ◽  
...  
Keyword(s):  
Mental Health ◽  
Young Adults ◽  
Young People ◽  
Case Series ◽  
Psychotic Episode ◽  
Published Data ◽  
Growing Up ◽  
Term Care ◽  
Perinatally Acquired

Abstract Background Increasing numbers of children with perinatally acquired HIV (PaHIV) are transitioning into adult care. People living with behaviourally acquired HIV are known to be at more risk of psychosis than uninfected peers. Young adults living with PaHIV face numerous risk factors; biological: lifelong exposure to a neurotrophic virus, antiretroviral medication and immune dysfunction during brain development, and environmental; social deprivation, ethnicity-related discrimination, and migration-related issues. To date, there is little published data on the prevalence of psychotic illness in young people growing up with PaHIV. Methods We conducted a retrospective case note review of all individuals with PaHIV aged over 18 years registered for follow up at a dedicated clinic in the UK (n = 184). Results In total, 12/184 (6.5%), median age 23 years (interquartile range 21–26), had experienced at least one psychotic episode. The presentation and course of the psychotic episodes experienced by our cohort varied from short-lived symptoms to long term illness and nine (75%) appear to have developed a severe and enduring mental illness requiring long term care. Conclusion The prevalence of psychosis in our cohort was clearly above the lifetime prevalence of psychosis in UK individuals aged 16–34 years, which has been reported to be 0.5–1.0%. This highlights the importance of clinical vigilance regarding the mental health of young people growing up with PaHIV and the need to integrate direct access to mental health services within the HIV centres providing medical care.

scholarly journals Validating the wheelchair outcome measure for residents in long-term care

2013 ◽  
Vol 9 (3) ◽  
pp. 209-212 ◽  
Author(s):  
Shahriar Parvaneh ◽  
William B. Mortenson ◽  
William C. Miller
Keyword(s):  
Long Term Care ◽  
Outcome Measure ◽  
Term Care

Phenotype Analysis and Genetic Study of Chinese Patients With Treacher Collins Syndrome

2021 ◽  
pp. 105566562110375
Author(s):  
Meng Lu ◽  
Bin Yang ◽  
Zixiang Chen ◽  
Haiyue Jiang ◽  
Bo Pan
Keyword(s):  
Rare Variants ◽  
Clinical Care ◽  
Treacher Collins Syndrome ◽  
Chinese Patients ◽  
Pathogenic Variants ◽  
Premature Termination Codons ◽  
Whole Exome ◽  
Exome Aggregation Consortium ◽  
Phenotype Analysis ◽  
Sporadic Cases

Objective The aim of this study was to confirm the pathogenic variants, explore the genotype–phenotype correlation and characteristics of Chinese patients with Treacher Collins syndrome (TCS). Design Clinical details of 3 TCS family cases and 2 sporadic cases were collected and analyzed. Whole-exome sequencing and Sanger sequencing were conducted to detect causative variants. Setting Tertiary clinical care. Patients This study included 8 patients clinically diagnosed with TCS who were from 3 familial cases and 2 sporadic cases. Main Outcome Measures When filtering the database, variants were saved as rare variants if their frequency were less than 0.005 in the 1000 Genomes Project Database, the Exome Aggregation Consortium (ExAC) browser, and the Novogene database, or they would be removed as common ones. The pathogenic variants identified were verified by polymerase chain reaction. The sequencing results were analyzed by Chromas 2.1 software. Results Two novel pathogenic variants (NM_000356.3: c.537del and NM_000356.3: c.1965_1966dupGG) and 2 known pathogenic variants (NM_000356.3: c.1535del, NM_000356.3: c.4131_4135del) were identified within TCOF1 which are predicted to lead to premature termination codons resulting in a truncated protein. There was a known missense SNP (NM_015972.3: c.139G>A) within POLR1D. No phenotype–genotype correlation was observed. Instead, these 8 patients demonstrated the high genotypic and phenotypic heterogeneity of TCS. Conclusions This study expands on the pathogenic gene pool of Chinese patients with TCS. Besides the great variation among patients which is similar to international reports, Chinese patients have their own characteristics in clinical phenotype and pathogenesis mutations.

scholarly journals Fucosidosis—Clinical Manifestation, Long-Term Outcomes, and Genetic Profile—Review and Case Series

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1383 ◽  
Author(s):  
Karolina M. Stepien ◽  
Elżbieta Ciara ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Neurodegenerative Disorder ◽  
Respiratory Infections ◽  
Clinical Manifestations ◽  
Case Series ◽  
Genetic Profile ◽  
Nonsense Mutations ◽  
Pathogenic Variants ◽  
One Stop ◽  
Stop Loss

Fucosidosis is a neurodegenerative disorder which progresses inexorably. Clinical features include coarse facial features, growth retardation, recurrent upper respiratory infections, dysostosis multiplex, and angiokeratoma corporis diffusum. Fucosidosis is caused by mutations in the FUCA1 gene resulting in α-L-fucosidase deficiency. Only 36 pathogenic variants in the FUCA1 gene are related to fucosidosis. Most of them are missense/nonsense substitutions; six missense and 11 nonsense mutations. Among deletions there were eight small and five gross changes. So far, only three splice site variants have been described—one small deletion, one complete deletion and one stop-loss mutation. The disease has a significant clinical variability, the cause of which is not well understood. The genotype–phenotype correlation has not been well defined. This review describes the genetic profile and clinical manifestations of fucosidosis in pediatric and adult cases.

scholarly journals P.075 Clinical spectrum of POLR3-related leukodystrophy caused by biallelic POLR1C pathogenic variants

2019 ◽  
Vol 46 (s1) ◽  
pp. S34
Author(s):  
L Gauquelin ◽  
FK Cayami ◽  
L Sztriha ◽  
G Yoon ◽  
LT Tran ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Craniofacial Development ◽  
Clinical Spectrum ◽  
Treacher Collins Syndrome ◽  
Cross Sectional ◽  
Related Disorder ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Motor Difficulties ◽  
Hypomyelinating Leukodystrophy

Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

scholarly journals Diagnostic exome sequencing in non-acquired focal epilepsies highlights a major role of GATOR1 complex genes

2020 ◽  
Vol 57 (9) ◽  
pp. 624-633 ◽  
Author(s):  
Martin Krenn ◽  
Matias Wagner ◽  
Christoph Hotzy ◽  
Elisabeth Graf ◽  
Sandrina Weber ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Rare Variants ◽  
Focal Epilepsy ◽  
Diagnostic Yield ◽  
Mammalian Target Of Rapamycin ◽  
High Rate ◽  
Molecular Heterogeneity ◽  
Pathogenic Variants ◽  
Uncertain Significance

BackgroundThe genetic architecture of non-acquired focal epilepsies (NAFEs) becomes increasingly unravelled using genome-wide sequencing datasets. However, it remains to be determined how this emerging knowledge can be translated into a diagnostic setting. To bridge this gap, we assessed the diagnostic outcomes of exome sequencing (ES) in NAFE.Methods112 deeply phenotyped patients with NAFE were included in the study. Diagnostic ES was performed, followed by a screen to detect variants of uncertain significance (VUSs) in 15 well-established focal epilepsy genes. Explorative gene prioritisation was used to identify possible novel candidate aetiologies with so far limited evidence for NAFE.ResultsES identified pathogenic or likely pathogenic (ie, diagnostic) variants in 13/112 patients (12%) in the genes DEPDC5, NPRL3, GABRG2, SCN1A, PCDH19 and STX1B. Two pathogenic variants were microdeletions involving NPRL3 and PCDH19. Nine of the 13 diagnostic variants (69%) were found in genes of the GATOR1 complex, a potentially druggable target involved in the mammalian target of rapamycin (mTOR) signalling pathway. In addition, 17 VUSs in focal epilepsy genes and 6 rare variants in candidate genes (MTOR, KCNA2, RBFOX1 and SCN3A) were detected. Five patients with reported variants had double hits in different genes, suggesting a possible (oligogenic) role of multiple rare variants.ConclusionThis study underscores the molecular heterogeneity of NAFE with GATOR1 complex genes representing the by far most relevant genetic aetiology known to date. Although the diagnostic yield is lower compared with severe early-onset epilepsies, the high rate of VUSs and candidate variants suggests a further increase in future years.

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