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The Cleft Palate-craniofacial Journal :... Mar 2020Children with Pierre Robin sequence (PRS) and cleft palate have a high rate of velopharyngeal insufficiency (VPI) following primary palatoplasty. Our purpose was to...
OBJECTIVE
Children with Pierre Robin sequence (PRS) and cleft palate have a high rate of velopharyngeal insufficiency (VPI) following primary palatoplasty. Our purpose was to determine the long-term incidence of speech-correcting surgeries (SCSs) and fistula rates in PRS after primary palatoplasty and the influence of possible causal factors.
DESIGN
A retrospective single-center, observational chart review study.
PARTICIPANTS
After exclusion, the study cohort comprised 78 nonsyndromic PRS children (48 females) born between 1990 and 2009 and treated at the Cleft Palate and Craniofacial Center of Helsinki University Hospital, Finland. Causal factors included gender, surgeon, age at primary palatoplasty, surgical technique, airway obstruction in infancy, and cleft severity. We analyzed the outcome at age 8 years and at data retrieval, with a median follow-up of 14 years (range: 8-27 years).
RESULTS
Thirty-four (43.6%) children received SCS by age 8 years, and of the 19 (24.4%) postoperative fistulas, 6 (7.7%) underwent closure. At data retrieval, 37 (47.4%) children had undergone SCS and 8 (10.3%) had a fistula closure. Median age at SCS was 6 years. The results showed no significant association for gender, surgeon, age at primary palatoplasty, surgical technique, cleft severity, or airway obstruction in infancy regarding incidence of SCS, fistulas, or repaired fistulas.
CONCLUSION
Pierre Robin sequence in children is associated with a high incidence of SCS and fistula formation, which necessitates accurate clinical follow-up and observation of speech development. The development of VPI in PRS is complex and most likely involving multiple factors.
Topics: Adolescent; Adult; Child; Cleft Palate; Female; Finland; Fistula; Humans; Incidence; Pierre Robin Syndrome; Postoperative Complications; Retrospective Studies; Speech; Treatment Outcome; Velopharyngeal Insufficiency; Young Adult
PubMed: 31530001
DOI: 10.1177/1055665619874991 -
The Journal of Craniofacial Surgery Sep 2020After a failed mandibular osteodistraction, the wrong positioned mandible of a few patients with Pierre Robin sequence returned in the most functional position and...
After a failed mandibular osteodistraction, the wrong positioned mandible of a few patients with Pierre Robin sequence returned in the most functional position and regained a proper symmetry, without external intervention. The study aims to explain this self-adjustment and introduce the floating bone phenomenon.The inclusion criteria were severe micrognathia, Fast and Early Mandibular Distraction Osteogenesis protocol, postoperative mandibular wrong positioning, presurgery, immediate postsurgery, and long-term computed tomography scan. Five patients were included. The considered parameters were the distance between mandibular dental centerline and midsagittal facial axis, the rotation of the mandibular body, the magnitude of elongation, and the lowering of the mandibular body.Three patients went from a decentralization >4 mm in the activation phase to a normalization of the said value in the follow-up. In the same period, the interincisal point of 2 patients moved respectively from 0.5 mm on the left and 0.8 mm on the right to 1.2 mm and 1.6 mm on the right, respectively. The rotation of the mandibular body was meanly 25.6° among all patients. The mean value of the distraction was 14.1 mm. A difference of about 4.4 mm between the left and the right side was measured. The lowering of the mandible varied between 2.8 and 12.6 mm.All patients improved their symmetry. Four of them improved in all the measured parameters, while 1 patient presented a worsening in the decentralization of the interincisal point.The floating bone phenomenon could break new grounds in the management of patients with Pierre Robin sequence.
Topics: Humans; Mandible; Osteogenesis, Distraction; Pierre Robin Syndrome; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32282671
DOI: 10.1097/SCS.0000000000006405 -
Archives of Disease in Childhood. Fetal... Mar 2020Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin...
OBJECTIVE
Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS.
DESIGN/SETTING
This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011.
PATIENTS
Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview.
RESULTS
Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2).
CONCLUSIONS
These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.
Topics: Adult; Case-Control Studies; Cleft Palate; Comorbidity; Europe; Female; Gestational Age; Humans; Infant, Newborn; Male; Methadone; Opioid-Related Disorders; Pierre Robin Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Risk Assessment
PubMed: 31229957
DOI: 10.1136/archdischild-2019-316804 -
Seminars in Fetal & Neonatal Medicine Dec 2021Approximately 5% of children experience difficulty with the complex coordination of sucking, swallowing and breathing required for feeding. Infants with craniofacial... (Review)
Review
Approximately 5% of children experience difficulty with the complex coordination of sucking, swallowing and breathing required for feeding. Infants with craniofacial malformations may have anatomic and neurologic contributions to feeding problems. Examples include cleft lip and/or palate, micrognathia, maxillary hypoplasia, and pharyngeal dysfunction. Interventions may facilitate weight gain and avoid failure-to-thrive in these infants. An interdisciplinary approach to address feeding challenges in children with craniofacial differences is necessary. Positional changes, latching maneuvers, specialized feeder nipples, squeezable bottles, and cup feeding can be implemented early. Surgical intervention, including gastrostomy tube placement, tongue lip adhesion, mandibular distraction osteogenesis and tracheostomy, may be required in more severe cases.
Topics: Airway Obstruction; Child; Cleft Lip; Cleft Palate; Humans; Infant; Mandible; Osteogenesis, Distraction; Pierre Robin Syndrome; Retrospective Studies
PubMed: 34561178
DOI: 10.1016/j.siny.2021.101280 -
Oral Diseases Sep 2023This study aims to review the pathogenic mechanisms and clinical manifestations in syndromes with tooth agenesis (TA). Online Mendelian Inheritance in Man and PubMed... (Review)
Review
This study aims to review the pathogenic mechanisms and clinical manifestations in syndromes with tooth agenesis (TA). Online Mendelian Inheritance in Man and PubMed databases were searched for a comprehensive review. Previous publications reported complicated aetiologies of syndromic TA. Gene mutations in conserved signalling pathways (WNT, EDA, SHH, FGF, and TGF-β/BMP) and crucial molecules (PAX9, PIXT2, IRF6, the p53 family, and subunits of RNA polymerase III) are the main causes of syndromic TA. In the process of odontogenesis, antagonistic or synergistic interactions are demonstrated in patients and murine models. Mutations in some genes (WNT10A, WNT10B, AXIN2, ANTXR1, MSX1, EDA, EDAR, and EDARADD) can result in both syndromic and isolated TA. In addition, chromosomal anomalies are also responsible for syndromic TA (Down syndrome, Wolf-Hirschhorn syndrome, Williams syndrome, and Pierre Robin sequence). The causes and manifestations of syndromic TA are highly complex, and this constitutes a clinical challenge. Mutations in signalling pathways and crucial molecules as well as chromosomal anomalies are responsible for syndromic TA. And there are overlaps between the causative genes of syndromic and isolated TA.
Topics: Animals; Mice; Syndrome; Anodontia; Mutation; Chromosome Aberrations; Signal Transduction; Interferon Regulatory Factors
PubMed: 36219525
DOI: 10.1111/odi.14402 -
American Journal of Medical Genetics.... Jan 2022Robin sequence (RS), the triad of micrognathia, glossoptosis, and airway obstruction, is a major cause of respiratory distress and feeding difficulties in neonates....
Robin sequence (RS), the triad of micrognathia, glossoptosis, and airway obstruction, is a major cause of respiratory distress and feeding difficulties in neonates. Robin sequence can be associated with other medical or developmental comorbidities in ~50% of cases ("syndromic" RS). As well, RS is variably associated with cleft palate (CP). Previous studies have not investigated differences in clinical characteristics of children with RS based on presence or absence of CP. We retrospectively reviewed 175 children with RS and compared genetic diagnoses, medical and developmental comorbidities, severity of airway obstruction, and feeding outcomes between those with and without CP. Strikingly, 45 of 45 (100%) children with RS without CP were classified as syndromic due to presence of comorbidities unrelated to RS, while 83 of 130 (64%) children with RS with CP were classified as syndromic. Among 128 children with syndromic RS, there were no differences in severity of airway obstruction, surgical intervention rate or type, or feeding outcome at 12 months based on CP status. Our findings support the conclusion that the pathogenesis of RS without CP is distinct from RS with CP and more likely to cause additional medical or developmental problems. Alternatively, children with RS without CP and without additional anomalies present may be under recognized.
Topics: Airway Obstruction; Child; Cleft Palate; Humans; Infant, Newborn; Micrognathism; Pierre Robin Syndrome; Retrospective Studies
PubMed: 34569146
DOI: 10.1002/ajmg.a.62515 -
American Journal of Human Genetics Jun 2021ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a...
ANKRD17 is an ankyrin repeat-containing protein thought to play a role in cell cycle progression, whose ortholog in Drosophila functions in the Hippo pathway as a co-factor of Yorkie. Here, we delineate a neurodevelopmental disorder caused by de novo heterozygous ANKRD17 variants. The mutational spectrum of this cohort of 34 individuals from 32 families is highly suggestive of haploinsufficiency as the underlying mechanism of disease, with 21 truncating or essential splice site variants, 9 missense variants, 1 in-frame insertion-deletion, and 1 microdeletion (1.16 Mb). Consequently, our data indicate that loss of ANKRD17 is likely the main cause of phenotypes previously associated with large multi-gene chromosomal aberrations of the 4q13.3 region. Protein modeling suggests that most of the missense variants disrupt the stability of the ankyrin repeats through alteration of core structural residues. The major phenotypic characteristic of our cohort is a variable degree of developmental delay/intellectual disability, particularly affecting speech, while additional features include growth failure, feeding difficulties, non-specific MRI abnormalities, epilepsy and/or abnormal EEG, predisposition to recurrent infections (mostly bacterial), ophthalmological abnormalities, gait/balance disturbance, and joint hypermobility. Moreover, many individuals shared similar dysmorphic facial features. Analysis of single-cell RNA-seq data from the developing human telencephalon indicated ANKRD17 expression at multiple stages of neurogenesis, adding further evidence to the assertion that damaging ANKRD17 variants cause a neurodevelopmental disorder.
Topics: Adolescent; Adult; Child; Child, Preschool; Craniofacial Abnormalities; Female; Haploinsufficiency; Heterozygote; Humans; Infant; Intellectual Disability; Language Development Disorders; Loss of Function Mutation; Male; Pedigree; Phenotype; RNA-Binding Proteins; Signal Transduction; Syndrome; Young Adult
PubMed: 33909992
DOI: 10.1016/j.ajhg.2021.04.007 -
Indian Journal of Otolaryngology and... Sep 2021Hereditary hearing loss accounts for nearly 60% of deafness in developed countries and about 30% of them are syndromic. Pierre Robin Syndrome is one such condition. The...
Hereditary hearing loss accounts for nearly 60% of deafness in developed countries and about 30% of them are syndromic. Pierre Robin Syndrome is one such condition. The patient with this syndrome usually presnts with triad of micrognathia, glossoptosis and cleft palate. Hearing loss is mostly conductive but there can be sensorineural hearing loss also. Here we present a case of Pierre Robin Syndrome who presented with congenital hearing loss. He also had bilateral serous otitis media. He underwent cochlear implant surgery and was prescribed antihistaminics and steroid spray for middle ear effusion. Therefore, proper clinical evaluation is required.
PubMed: 34471629
DOI: 10.1007/s12070-020-02331-9 -
The Cleft Palate-craniofacial Journal :... Jan 2021The aim of this study was to compare the dentoskeletal pattern of Treacher Collins syndrome (TCS) and nonsyndromic Pierre Robin sequence (PRS).
OBJECTIVE
The aim of this study was to compare the dentoskeletal pattern of Treacher Collins syndrome (TCS) and nonsyndromic Pierre Robin sequence (PRS).
DESIGN
Retrospective.
SETTING
Single center.
PATIENTS
Eighteen patients diagnosed with TCS (Group TCS) or PRS (Group PRS) in rehabilitation treatment at a single center. Group TCS was composed of 9 patients (4 male, 5 female) with a mean age of 12.9 years (standard deviation = 4.8). Group PRS was composed of 9 patients paired by age and sex with group TCS.
MAIN OUTCOME MEASURE(S)
Cone beam computed tomography-derived cephalometric images taken before the orthodontic or the orthodontic-surgical treatment were analyzed using Dolphin Imaging (Dolphin Imaging 11.0 & Management Solutions). Variables evaluating the cranial base, the maxillary and mandibular skeletal components, maxillomandibular relationship, the vertical components and the dentoalveolar region were measured. Intergroup comparisons were performed using tests. The significance level considered was 5%.
RESULTS
Intergroup differences in the mandible size and growth pattern were observed. Group TCS showed a smaller mandibular length (Co-Go, Co-Gn) and a higher palatal plane (SN-Palatal Plane) and mandibular plane angles (SN-Go.Gn) compared to group PRS. No differences between TCS and PRS were observed for the sagittal position of the maxilla, maxillomandibular relationship, and dental components.
CONCLUSIONS
Treacher Collins syndrome presented a decreased mandible and a more severe vertical growth pattern compared to PRS.
Topics: Cephalometry; Female; Humans; Male; Mandible; Mandibulofacial Dysostosis; Pierre Robin Syndrome; Retrospective Studies
PubMed: 32613853
DOI: 10.1177/1055665620937499 -
Seminars in Fetal & Neonatal Medicine Dec 2021Robin sequence (RS) is diagnosed in infants born with micrognathia, glossoptosis and varying degrees of upper airway obstruction (UAO). Due to the variable levels of... (Review)
Review
Robin sequence (RS) is diagnosed in infants born with micrognathia, glossoptosis and varying degrees of upper airway obstruction (UAO). Due to the variable levels of hypoxia, severe breathing and feeding problems can occur. Treatment is determined by clinical severity, ranging from conservative interventions for mild cases to surgical interventions for severe cases. Mandibular distraction osteogenesis (MDO) is a surgical technique that gradually lengthens the mandible after an osteotomy by using an internal or external distraction device, directly correcting the micrognathia. This review will focus on advantages and disadvantages of mandibular distraction in infants with RS.
Topics: Airway Obstruction; Humans; Infant; Mandible; Osteogenesis, Distraction; Pierre Robin Syndrome; Retrospective Studies; Treatment Outcome
PubMed: 34663561
DOI: 10.1016/j.siny.2021.101283