-
Pediatric and Developmental Pathology :... 2024Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically...
Coffin-Siris syndrome is an autosomal dominant disorder with neurological, cardiovascular, and gastrointestinal symptoms. Patients with Coffin-Siris syndrome typically have variable degree of developmental delay or intellectual disability, muscular hypotonia, dysmorphic facial features, sparse scalp hair, but otherwise hirsutism and fifth digit nail or distal phalanx hypoplasia or aplasia. Coffin-Siris syndrome is caused by pathogenic variants in 12 different genes including and . Pathogenic gene variants cause Coffin-Siris syndrome 3 whereas pathogenic gene variants cause Coffin-Siris syndrome 2. Here, we present two prenatal Coffin-Siris syndrome cases with autosomal dominant pathogenic variants: gene c.1066_1067del, p.(Leu356AspfsTer4) variant, and a novel gene c.1920+3_1920+6del variant. The prenatal phenotype in Coffin-Siris syndrome has been rarely described. This article widens the phenotypic spectrum of prenatal Coffin-Siris syndrome with severely hypoplastic right ventricle with VSD and truncus arteriosus type III, persisting left superior and inferior caval vein, bilateral olfactory nerve aplasia, and hypoplastic thymus. A detailed clinical description of the patients with ultrasound, MRI, and pictures of the affected fetuses showing the wide phenotypic spectrum of the disease is presented.
Topics: Humans; Intellectual Disability; Abnormalities, Multiple; Face; Phenotype; Hand Deformities, Congenital; Micrognathism; Neck
PubMed: 37981638
DOI: 10.1177/10935266231210155 -
Plastic and Reconstructive Surgery Jul 2024Studies of infants with micrognathia, especially Robin sequence, are limited by its rarity and both phenotypic and diagnostic variability. Most knowledge of this...
BACKGROUND
Studies of infants with micrognathia, especially Robin sequence, are limited by its rarity and both phenotypic and diagnostic variability. Most knowledge of this condition is sourced from small, single-institution samples.
METHODS
This is a cross-sectional study including infants with micrognathia admitted to 38 Children's Hospital Neonatal Consortium centers from 2010 through 2020. Predictor variables included demographic data, birth characteristics, cleft, and syndrome status. Outcome variables included length of stay, death, feeding or respiratory support, and secondary airway operations.
RESULTS
A total of 1289 infants with micrognathia had surgery to correct upper airway obstruction. Mean age and weight at operation were 34.8 ± 1.8 weeks and 3515.4 ± 42 g, respectively. A syndromic diagnosis was made in 150 (11.6%) patients, with Stickler (5.4%) and Treacher Collins (2.2%) syndromes being the most common. Operations included mandibular distraction osteogenesis (MDO) in 66.3%, tracheostomy in 25.4%, and tongue-lip adhesion (TLA) in 8.3%. Patients receiving a tracheostomy had lower birthweight, head circumference, gestational age, and Apgar scores. Patients undergoing MDO were less likely to need a second airway operation compared with patients undergoing TLA (3.5% versus 17.8%; P < 0.001). The proportion of infants feeding exclusively orally at hospital discharge differed significantly, from most to least: MDO, TLA, and tracheostomy. Hospital length of stay was not statistically different for patients who had MDO or TLA, but was longer for those with primary tracheostomy. The mortality rate was low for all operations (0.5%).
CONCLUSIONS
In this surgical patient cohort, MDO was associated with shorter hospital stay, improved oral feeding, and lower rates of secondary airway operations. Prospective multicenter studies are necessary to support these conclusions.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, III.
Topics: Humans; Cross-Sectional Studies; Male; Female; Micrognathism; Infant; Treatment Outcome; Infant, Newborn; Length of Stay; Airway Obstruction; Osteogenesis, Distraction; Tracheostomy
PubMed: 37184511
DOI: 10.1097/PRS.0000000000010639 -
Cranio : the Journal of... Nov 2023To evaluate whether there is a difference between the effects of Bionator and Forsus appliances on airway volume.
OBJECTIVE
To evaluate whether there is a difference between the effects of Bionator and Forsus appliances on airway volume.
METHODS
Forty patients with mandibular retrognathia were divided into two groups. The Bionator appliance was applied to Group 1, while the Forsus FRD EZ2 appliance was applied to Group 2. Three-dimensional images were captured before and after functional appliance use in both groups. Dolphin 3D software was used for airway measurements.
RESULTS
No statistically significant difference was found between the groups in terms of volumetric and area measurements. There was a statistically significant difference between the minimum axial T and O-N border T measurements of the groups.
CONCLUSION
The use of functional appliances may contribute to an increase in oropharyngeal airway dimensions, but there was no difference between the Bionator and Forsus groups in terms of volumetric measurements.
Topics: Humans; Activator Appliances; Orthodontic Appliances, Functional; Retrognathia; Mandible; Malocclusion, Angle Class II; Cephalometry; Micrognathism
PubMed: 36394427
DOI: 10.1080/08869634.2022.2147283 -
European Journal of Medical Genetics Jun 2024Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly... (Review)
Review
Anorectal malformations (ARMs) represent a wide spectrum of congenital anomalies of the anus and rectum, of which more than half are syndromic. Their etiology is highly heterogeneous and still poorly understood. We report a 4-year-old girl who initially presented with an isolated ARM, and subsequently developed a global developmental delay as part of an ARID1B-related Coffin-Siris syndrome (CSS). A co-occurrence of ARMs and CSS in an individual by chance is unexpected since both diseases are very rare. A review of the literature enabled us to identify 10 other individuals with both CSS and ARMs. Among the ten individuals reported in this study, 8 had a variant in ARID1A, 2 in ARID1B, and 1 in SMARCA4. This more frequent than expected association between CSS and ARM indicates that some ARMs are most likely part of the CSS spectrum, especially for ARID1A-related CSS.
Topics: Humans; Female; Micrognathism; Child, Preschool; Intellectual Disability; Transcription Factors; Neck; Hand Deformities, Congenital; Abnormalities, Multiple; DNA-Binding Proteins; Anorectal Malformations; Face; DNA Helicases; Nuclear Proteins; Anal Canal; Phenotype
PubMed: 38735569
DOI: 10.1016/j.ejmg.2024.104948 -
Journal of the College of Physicians... Feb 2024To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and...
OBJECTIVE
To evaluate the correlation of cerebrospinal fluid total protein and serum neutrophil-to-lymphocyte ratio with the clinical outcomes and the various clinical and electrophysiological variants of Guillain-Barre syndrome.
STUDY DESIGN
Cross-sectional study. Place and Duration of the Study: Department of Neurology, Mayo Hospital and King Edward Medical University, Lahore, Pakistan, from November 2022 to April 2023.
METHODOLOGY
Fourty-six Guillain-Barre syndrome patients, aged 12-70 years, were included in the study diagnosed by using the Brighton's criteria. Functional disability and respiratory insufficiency were assessed by using the modified Hughes disability score and the Erasmus Guillain-Barre syndrome respiratory insufficiency score, respectively. Serum neutrophil-to-lymphocyte ratio and cerebrospinal fluid total protein were calculated for each patient at the time of admission.
RESULTS
Axonal variants had a higher mean neutrophil-to-lymphocyte ratio (5.29 ± 4.38) than demyelinating variants (4.71 ± 3.4) and Miller-Fischer syndrome (3 ± 2.828). This ratio was positively correlated with the modified Hughes's disability score (r = 0.790, p = 0.001) and the Erasmus Guillain-Barre syndrome respiratory insufficiency score (r = 0.936, p = 0.002). Mean cerebrospinal fluid total protein was higher for demyelinating (218 ± 136 mg/dl) than axonal variants (86 ± 56 mg/dl) and Miller-Fischer syndrome (34 ± 21 mg/dl). However, higher modified Hughes disability score (4-6) (r = 0.020, p = 0.117) and a high Erasmus Guillain-Barre syndrome respiratory insufficiency score (5-7) (r = 0.115, p = 0.302) did not significantly affect mean cerebrospinal fluid total proteins.
CONCLUSION
Serum neutrophil-to-lymphocyte ratio can be regarded as a reliable biomarker to assess disease severity and clinical outcome in Guillain-Barre syndrome. Cerebrospinal fluid total protein is a poor predictor of the prognosis and severity of Guillain-Barre syndrome.
KEY WORDS
Guillain-Barre syndrome (GBS), Clinical outcome, Cerebrospinal fluid total protein (CSF-TP), Neutrophil-to-lymphocytic ratio (NLR), Prognostic biomarker.
Topics: Humans; Guillain-Barre Syndrome; Neutrophils; Cross-Sectional Studies; Biomarkers; Lymphocytes; Respiratory Insufficiency; Chromosome Deletion; WAGR Syndrome; Abnormalities, Multiple; Limb Deformities, Congenital; Mandibulofacial Dysostosis; Micrognathism; Chromosomes, Human, Pair 11
PubMed: 38342870
DOI: 10.29271/jcpsp.2024.02.187 -
The Laryngoscope Apr 2024Surgically assisted rapid palatal expansion (SARPE) addresses transverse maxillary deficiency, a known contributor to nasal obstruction. The purpose of this study was to...
OBJECTIVE
Surgically assisted rapid palatal expansion (SARPE) addresses transverse maxillary deficiency, a known contributor to nasal obstruction. The purpose of this study was to assess the feasibility, preliminary outcomes, and safety of posterior palatal expansion via subnasal endoscopy (2PENN), a modified SARPE procedure, aimed at achieving anterior and posterior maxillary expansion.
METHODS
This prospective case series included consecutive adult patients with findings of transverse maxillary deficiency that underwent the 2PENN procedure from 4/2021 to 4/2022. Patients completed pre- and post-operative clinical evaluations, Nasal Obstruction and Septoplasty Effectiveness (NOSE) questionnaires, and computed tomography (CT), with measures including expansion at the level of the posterior nasal spine (PNS), first maxillary inter-molar distance (IMD), and anterior nasal spine (ANS).
RESULTS
The cohort (N = 20) was middle-aged (39 ± 11 years), predominantly male (80%), and overweight (BMI 28 ± 4 kg/m ). The majority (85%) of patients had sleep breathing issues, of which 10 (59%) had polysomnography-confirmed obstructive sleep apnea (OSA). Full anterior-posterior separation of the mid-palatal suture line was evident on all post-operative CT scans, with mean expansion at the PNS of 3.6 ± 1.3 mm, IMD of 6.1 ± 1.6 mm and ANS of 7.0 ± 1.6 mm (p < 0.001). Following surgery, mean NOSE scores improved from 57 ± 23 to 14 ± 13 (p < 0.001). One patient required maxillary antrostomy for post-operative sinusitis.
CONCLUSION
2PENN is an effective and safe technique for achieving both anterior and posterior maxillary expansion in patients with transverse maxillary deficiency. Further study is warranted to better understand the effect of 2PENN in patients with OSA, particularly as it relates to improving pharyngeal patency.
LEVEL OF EVIDENCE
4 Laryngoscope, 134:1970-1977, 2024.
Topics: Adult; Middle Aged; Humans; Male; Female; Palatal Expansion Technique; Pilot Projects; Nasal Obstruction; Sleep Apnea, Obstructive; Endoscopy, Gastrointestinal; Micrognathism; Maxilla
PubMed: 37772955
DOI: 10.1002/lary.31060 -
Morphologie : Bulletin de L'Association... May 2024In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary...
OBJECTIVES
In addition to bone fragility, patients with osteogenesis imperfecta (OI) type III have typical craniofacial abnormalities, such as a triangular face and maxillary micrognathism. However, in the osteogenesis imperfecta mouse (oim), a validated model of OI type III, few descriptions exist of craniofacial phenotype. Treatment of OI mostly consists of bisphosphonate administration. Cathepsin K inhibition has been tested as a promising therapeutic approach for osteoporosis and positive results were observed in long bones of cathepsin K knocked out oim (oim/CatK). This craniometry study aimed to highlight the craniofacial characteristics of oim and Cathepsin K KO mouse.
MATERIALS AND METHODS
We analyzed the craniofacial skeleton of 51 mice distributed in 4 genotype groups: Wt (control), oim, CatK, oim/CatK. The mice were euthanized at 13 weeks and their heads were analyzed using densitometric (pQCT), X-ray cephalometric, and histomorphometric methods.
RESULTS
The craniofacial skeleton of the oim mouse is frailer than the Wt one, with a reduced thickness and mineral density of the cranial vault and mandibular ramus. Different cephalometric data attest a dysmorphism similar to the one observed in humans with OI type III. Those abnormalities were not improved in the oim/CatK group.
CONCLUSION
These results suggest that oim mouse could serve as a complete model of the human OI type III, including the craniofacial skeleton. They also suggest that invalidation of cathepsin K has no impact on the craniofacial abnormalities of the oim model.
PubMed: 38788496
DOI: 10.1016/j.morpho.2024.100785 -
European Journal of Human Genetics :... Aug 2023
Topics: Humans; Growth Disorders; Micrognathism; Congenital Microtia; Patella
PubMed: 37248383
DOI: 10.1038/s41431-023-01397-7 -
European Journal of Medical Genetics Jun 2024To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants...
To date 11 patients with Coffin-Siris syndrome type 7 (OMIM 618027) have been described since the first literature report. All reported patients carried de novo variants with presumed dominant negative effect, which localized in the PHD1/PHD2 domains of DPF2. Here we report on the first familial case of Coffin-Siris syndrome type 7. The index patient presented during the 1st year of life with failure to thrive and ectodermal anomalies. The genetic analysis using whole exome sequencing showed a likely pathogenic missense variant in the PHD1 region. The family analysis showed that the mother as well as the older brother of the index patient also carried the detected DPF2 variant in heterozygous state. The mother had a history of school difficulties but no history of failure to thrive and was overall mildly affected. The brother showed developmental delay with autistic features, ectodermal anomalies and overlapping morphologic features but did not have a history of growth failure problems. To our knowledge this is the first report of an inherited likely pathogenic variant in DPF2, underlining the variability of the associated phenotype as well as the importance of considering inherited DPF2 variants during the variant filtering strategy of whole exome data.
Topics: Adult; Female; Humans; Infant; Male; Abnormalities, Multiple; DNA-Binding Proteins; Face; Hand Deformities, Congenital; Intellectual Disability; Micrognathism; Mutation, Missense; Neck; Pedigree; Phenotype; Transcription Factors
PubMed: 38697389
DOI: 10.1016/j.ejmg.2024.104945 -
American Journal of Perinatology May 2024This study aimed to explore the efficiency of ultrasound (US) in prenatal diagnosis and prognosis of Pierre Robin sequence (PRS) of 18 cases.
OBJECTIVE
This study aimed to explore the efficiency of ultrasound (US) in prenatal diagnosis and prognosis of Pierre Robin sequence (PRS) of 18 cases.
STUDY DESIGN
A total of 79,305 women admitted for prenatal US examinations were recruited from January 2017 to December 2020. Eighteen cases of PRS fetuses were selected form the cohort and 40 cases of isolated micrognathia were recruited randomly as control group. All the clinical and imaging results were retrospectively reviewed. General condition, US measurements, and prognosis of fetuses were compared between groups.
RESULTS
Cleft palate, glossoptosis, and micrognathia were found in all 18 fetuses with PRS by prenatal US. Compared with the isolated micrognathia group, there were no significant differences in the PRS group in examination of maternal age, gestational weeks at assessment, and gender of fetuses, but significant lower measures in inferior facial angle, jaw index, and frontal nasal-mental angle (each < 0.05). Twelve fetuses were defined to have other associated malformations. Ear malformations were the most common associated malformations with a prevalence of 44.4% (8/18). All of the18 cases were confirmed with PRS after delivery or autopsy. Two delivered infants were found bucking easily, one baby was spitting up frequently but growth showed normal.
CONCLUSION
Prenatal detection of PRS with US examination is highly efficient. Even with the triad of malformations, isolated PRS had good outcomes following initial stabilization and management in the neonatal period. Prenatal detection of Pierre Robin syndrome with targeted US examination is efficient in discerning characteristics of this rare syndrome. Even with the triad of malformations, isolated PRS had good outcomes following initial stabilization and management in the neonatal period.
KEY POINTS
· Prenatal diagnosis of fetal PRS is of great clinical importance.. · Micrognathia has been identified as the primary feature of PRS.. · Posterior displacement of the tongue may cause acute neonatal respiratory distress.. · Even with triad malformation, isolated PRS seemed to have good outcomes..
Topics: Humans; Pierre Robin Syndrome; Female; Retrospective Studies; Pregnancy; Ultrasonography, Prenatal; Prognosis; Infant, Newborn; Micrognathism; Adult; Cleft Palate; Male; Glossoptosis; Gestational Age
PubMed: 37068514
DOI: 10.1055/s-0043-1768233