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International Journal of Pediatric... Apr 2018Craniofacial microsomia (CFM) is primarily characterized by underdevelopment of the ear and mandible, with several additional possible congenital anomalies. Despite the...
OBJECTIVE
Craniofacial microsomia (CFM) is primarily characterized by underdevelopment of the ear and mandible, with several additional possible congenital anomalies. Despite the potential burden of care and impact of CFM on multiple domains of functioning, few studies have investigated patient and caregiver perspectives. The objective of this study was to explore the diagnostic, treatment-related, and early psychosocial experiences of families with CFM with the aim of optimizing future healthcare delivery.
METHODS
Forty-two caregivers and nine adults with CFM responded to an online mixed-methods survey. Descriptive statistics and qualitative methods were used for the analysis.
RESULTS
Survey respondents reported high rates of subspecialty evaluations, surgeries, and participation in therapies. Some participants reported receiving inaccurate or incomplete information about CFM and experienced confusion about etiology. Communication about CFM among family members included mostly positive messages. Self-awareness of facial differences began at a mean age of three years and teasing at mean age six, with 43% of individuals four years or older reporting teasing. Teasing often involved name-calling and frequent reactions were ignoring and negative emotional responses. Participants ranked "understanding diagnosis and treatment" as a top priority for future research and had the most questions about etiology and treatment guidance.
CONCLUSIONS
The survey results on the healthcare and psychosocial experiences from birth through adulthood of individuals with CFM reinforce the need for ongoing psychological assessment and intervention. Healthcare provision could be improved through establishing diagnostic criteria and standardized treatment guidelines, as well as continued investigation of CFM etiology.
Topics: Adolescent; Adult; Caregivers; Child; Child, Preschool; Culture; Delivery of Health Care; Female; Goldenhar Syndrome; Health Surveys; Humans; Infant; Male; Patients; Physician-Patient Relations
PubMed: 29501301
DOI: 10.1016/j.ijporl.2018.02.007 -
Contemporary Clinical Dentistry Oct 2014Treacher Collins syndrome (TCS) or Franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable phenotypic expression. It presents...
Treacher Collins syndrome (TCS) or Franceschetti syndrome is an autosomal dominant disorder of craniofacial development with variable phenotypic expression. It presents with characteristic facial appearance enabling it to be easily recognizable. A case of a 10-year-old girl having TCS is briefly described in this article. A review of the etiology, clinical features, differential diagnosis, and treatment options are also discussed.
PubMed: 25395774
DOI: 10.4103/0976-237X.142826 -
American Journal of Speech-language... Nov 2019Purpose Youth with craniofacial microsomia (CFM) have anomalies and comorbidities that increase their risk for speech, language, and communication deficits. We examined...
Purpose Youth with craniofacial microsomia (CFM) have anomalies and comorbidities that increase their risk for speech, language, and communication deficits. We examined these outcomes in youth with and without CFM and explored differences as a function of CFM phenotype and hearing status. Method Participants included youth ages 11-17 years with CFM ( = 107) and demographically similar controls ( = 306). We assessed speech intelligibility, articulation, receptive and expressive language, and parent and teacher report measures of communication. Hearing status was also screened at the study visit. Group differences were estimated using linear regression analyses with standardized effect sizes (ES) adjusted for demographic characteristics (adjusted ES) or negative binomial regression. Results Youth with CFM scored lower than unaffected peers on most measures of intelligibility, articulation, expressive language, and parent- and-teacher-rated communication. Differences were most pronounced among participants with CFM who had mandibular hypoplasia plus microtia (adjusted ES = -1.15 to -0.18). Group differences were larger in youth with CFM who failed the hearing screen (adjusted ES = -0.73 to 0.07) than in those who passed the hearing screen (adjusted ES = -0.34 to 0.27). Conclusions Youth with CFM, particularly those with mandibular hypoplasia plus microtia and/or hearing loss, should be closely monitored for speech and language concerns. Further research is needed to identify the specific needs of youth with CFM as well as to document the course of speech and language development in children with CFM.
Topics: Adolescent; Child; Child Language; Communication; Communication Disorders; Female; Goldenhar Syndrome; Hearing Loss; Humans; Male; Phenotype; Regression Analysis; Speech Intelligibility
PubMed: 31580699
DOI: 10.1044/2019_AJSLP-19-0089 -
Cureus Feb 2023Objective Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) has a reported incidence of 1 in 3500 live births and requires intensive care and...
Objective Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) has a reported incidence of 1 in 3500 live births and requires intensive care and surgery. To evaluate the prevalence of a molecularly confirmed genetic etiology of EA/TEF in a level IV neonatal intensive care unit (NICU), focusing on genetic evaluation, diagnostic yield, and clinical outcomes of these neonates. Study design A retrospective cohort study over a period of seven years was performed for all patients admitted with a diagnosis of EA/TEF. Automated data was extracted for demographic information and manual extraction was done to evaluate the frequency of associated anomalies, type of genetic evaluations and diagnoses, and outcomes at NICU discharge. Results Sixty-eight infants met the inclusion criteria. The majority were male (n=42; 62%), born at >37 weeks' gestation (n=36; 53%), and had EA with distal TEF (n=54; 79%). Most (n=53; 78%) had additional associated congenital anomalies, but only 47 (69%) patients had a genetics evaluation performed and genetic testing was sent for 44 (65%) of those patients. The most common genetic testing performed was chromosomal microarray analysis (n=40; 59%), followed by chromosome analysis (n=11; 16%), and whole exome/genome sequencing (n=7; 10%). Five unique genetic diagnoses including CHARGE Syndrome, Fanconi Syndrome, EFTUD2-related mandibulofacial dysostosis, and two different chromosomal deletion syndromes were made for a total of nine (13%) patients in our cohort. The cohort suffered a high rate of morbidity and mortality during their NICU stay with important differences noted in isolated vs non-isolated EA/TEF. Twelve infants (18%) died prior to NICU discharge. Of those surviving, 40 (71%) infants had a primary repair, 37 (66%) infants required G or GJ feedings at NICU discharge, and eight (14%) patients were discharged on some type of respiratory support. Conclusion In this high-risk cohort of EA/TEF patients cared for at a quaternary NICU, a majority were non-isolated and had some form of a genetic evaluation, but a minority underwent exome or genome sequencing. Given the high prevalence of associated anomalies, high mortality, and genetic disease prevalence in this cohort, we recommend standardization of phenotyping and genetic evaluation to allow for precision care and appropriate risk stratification.
PubMed: 36909054
DOI: 10.7759/cureus.34779 -
BMJ Case Reports Aug 2019Mandibulofacial dysostosis with microcephaly (MFDM) is a rare condition that causes abnormalities of the head and face. Other major extracranial malformations may also...
Mandibulofacial dysostosis with microcephaly (MFDM) is a rare condition that causes abnormalities of the head and face. Other major extracranial malformations may also be found. The authors present a case of an MFDM in a 35 weeks newborn with antenatal growth restriction. The patient required resuscitation at birth and was diagnosed with oesophageal atresia with tracheoesophageal fistula at day 1. At physical examination he presented multiple congenital malformations including prominent forehead, plagiocephaly, low-set ears, malformed auricles, hypertelorism, downward-slanting eyes, micrognathia, everted lower lip, short neck, wide-spaced nipples and inguinal hernia. Imaging investigation showed dysplasia of the inner ear with agenesis of the vestibular-cochlear nerves and global cerebral atrophy. Analysis of the EFTUD2 gene revealed that the patient was a heterozygous carrier of a pathogenic mutation (c.831_832del[p.Lys277Asnsf*7]), which has not been previously described. This case illustrates the challenges faced in diagnosing and treating MFDM patients.
Topics: Abnormalities, Multiple; Diagnosis, Differential; Esophageal Atresia; Humans; Infant, Newborn; Infant, Premature; Magnetic Resonance Imaging; Male; Mandibulofacial Dysostosis; Microcephaly; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear; Syndrome
PubMed: 31413053
DOI: 10.1136/bcr-2019-229831 -
BMC Medical Genetics Sep 2020Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major...
BACKGROUND
Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant genetic disease characterized by intellectual and growth retardations, as well as major microcephaly, induced by missense and splice site variants or microdeletions in the EFTUD2 gene.
CASE PRESENTATION
Here, we investigate the case of a young girl with symptoms of MFDM and a normal karyotype. Whole-exome sequencing of the family was performed to identify genetic alterations responsible for this phenotype. We identified a de novo synonymous variant in the EFTUD2 gene. We demonstrated that this synonymous variant disrupts the donor splice-site in intron 9 resulting in the skipping of exon 9 and a frameshift that leads to a premature stop codon.
CONCLUSIONS
We present the first case of MFDM caused by a synonymous variant disrupting the donor splice site, leading to exon skipping.
Topics: Base Sequence; Child; Female; Humans; Karyotype; Mandibulofacial Dysostosis; Microcephaly; Mutation; Peptide Elongation Factors; Phenotype; RNA Splicing; Ribonucleoprotein, U5 Small Nuclear
PubMed: 32943010
DOI: 10.1186/s12881-020-01121-y -
European Journal of Human Genetics :... Oct 2022Oculo-auriculo-vertebral syndrome (OAVS) is a clinically heterogeneous disorder, with both genetic and environmental contributors. Multiple genes have been associated...
Oculo-auriculo-vertebral syndrome (OAVS) is a clinically heterogeneous disorder, with both genetic and environmental contributors. Multiple genes have been associated with OAVS and common molecular pathways, such as retinoic acid and the PAX-SIX-EYA-DACH (PSED) network, are being implicated in the disease pathophysiology. Biallelic homozygous nonsense or hypomorphic missense mutations in PAX1 cause otofaciocervical syndrome type 2 (OTFCS2), a similar but more severe multi-system disorder that can be accompanied by severe combined immunodeficiency due to thymic aplasia. Here we have identified a multi-generational family with mild features of OAVS segregating a heterozygous frameshift in PAX1. The four base duplication is expected to result in nonsense-mediated decay, and therefore cause a null allele. While there was full penetrance of the variant, expressivity of facial and ear features were variable. Our findings indicate there can be monoallelic and biallelic disorders associated with PAX1, and further implicate the PSED network in OAVS.
Topics: Goldenhar Syndrome; Homozygote; Humans; Mutation, Missense; Paired Box Transcription Factors; Severe Combined Immunodeficiency; Tretinoin
PubMed: 35879406
DOI: 10.1038/s41431-022-01154-2 -
American Journal of Human Genetics May 2015We report three individuals with a cranioskeletal malformation syndrome that we define as acrofacial dysostosis, Cincinnati type. Each individual has a heterozygous...
We report three individuals with a cranioskeletal malformation syndrome that we define as acrofacial dysostosis, Cincinnati type. Each individual has a heterozygous mutation in POLR1A, which encodes a core component of RNA polymerase 1. All three individuals exhibit varying degrees of mandibulofacial dysostosis, and two additionally have limb anomalies. Consistent with this observation, we discovered that polr1a mutant zebrafish exhibited cranioskeletal anomalies mimicking the human phenotype. polr1a loss of function led to perturbed ribosome biogenesis and p53-dependent cell death, resulting in a deficiency of neural-crest-derived skeletal precursor cells and consequently craniofacial anomalies. Our findings expand the genotypic and phenotypic heterogeneity of congenital acrofacial disorders caused by disruption of ribosome biogenesis.
Topics: Animals; Cell Death; Genotype; Humans; Limb Deformities, Congenital; Mandibulofacial Dysostosis; Mutation; Neural Crest; RNA Polymerase I; Ribosomes; Zebrafish
PubMed: 25913037
DOI: 10.1016/j.ajhg.2015.03.011 -
The Cleft Palate-craniofacial Journal :... Aug 2019The Craniofacial microsomia: Longitudinal Outcomes in Children pre-Kindergarten (CLOCK) study is a longitudinal cohort study of neurobehavioral outcomes in infants and...
OBJECTIVE
The Craniofacial microsomia: Longitudinal Outcomes in Children pre-Kindergarten (CLOCK) study is a longitudinal cohort study of neurobehavioral outcomes in infants and toddlers with craniofacial microsomia (CFM). In this article, we review the data collection and methods used to characterize this complex condition and describe the demographic and clinical characteristics of the cohort.
SETTING
Craniofacial and otolaryngology clinics at 5 study sites.
PARTICIPANTS
Infants with CFM and unaffected infants (controls) ages 12 to 24 months were recruited from the same geographical regions and followed to age 36 to 48 months.
METHODS
Phenotypic, neurodevelopmental, and facial expression assessments were completed during the first and third waves of data collection (time 1 and time 3, respectively). Medical history data were taken at both of these time points and during an intermediate parent phone interview (time 2).
RESULTS
Our cohort includes 108 cases and 84 controls. Most cases and controls identified as white and 55% of cases and 37% of controls identified as Hispanic. Nearly all cases had microtia (95%) and 59% had mandibular hypoplasia. Cases received extensive clinical care in infancy, with 59% receiving care in a craniofacial clinic and 28% experiencing at least one surgery. Study visits were completed at a study site (92%) or at the participant's home (8%).
CONCLUSIONS
The CLOCK study represents an effort to overcome the challenges of characterizing the phenotypic and neurodevelopmental outcomes of CFM in a large, demographically and geographically diverse cohort.
Topics: Child, Preschool; Cohort Studies; Congenital Microtia; Female; Goldenhar Syndrome; Humans; Infant; Longitudinal Studies; Male; Treatment Outcome; United States
PubMed: 30621445
DOI: 10.1177/1055665618821014 -
The American Journal of Occupational... 2021Knowledge of unmet school participation needs for students with craniofacial microsomia (CFM) can inform decisions regarding intervention support.
IMPORTANCE
Knowledge of unmet school participation needs for students with craniofacial microsomia (CFM) can inform decisions regarding intervention support.
OBJECTIVE
To compare students with and without CFM on school participation (i.e., frequency, involvement, desire for participation to change) and caregivers' perceptions of environmental support for participation in occupations.
DESIGN
Cross-sectional design using secondary analyses of a subset of data.
SETTING
Multisite cohort study.
PARTICIPANTS
Caregivers of students with CFM (n = 120) and of students without CFM (n = 315), stratified by history of education- and health-related service use.
OUTCOMES AND MEASURES
School participation and environmental support, obtained with the Participation and Environment Measure-Children and Youth.
RESULTS
Significant group differences were found in frequency of school participation (effect size [ES] = -0.38, 95% confidence interval [-0.64, -0.12], p = .005), level of involvement (ES = -0.14, p = .029), and desired change (p = .001), with students with CFM exhibiting greater participation restriction than students without CFM and no history of service use. No statistically significant group differences were found in environmental support for participation in the school setting. Item-level findings showed statistically significant higher desire for participation to change in three of five school occupations (odds ratio = 1.77-2.39, p = .003-.045) for students with CFM compared with students without CFM and no history of service use.
CONCLUSIONS AND RELEVANCE
The results suggest that students with CFM experience restriction in participation at school.
WHAT THIS ARTICLE ADDS
Students with CFM may benefit from targeted school-based interventions to optimize their inclusion.
Topics: Adolescent; Caregivers; Child; Cohort Studies; Cross-Sectional Studies; Goldenhar Syndrome; Humans; School Health Services; Schools; Students
PubMed: 33657352
DOI: 10.5014/ajot.2021.041277