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Journal of Pediatric Hematology/oncology Mar 2024Bloom syndrome (BS) is a rare autosomal recessive inherited disorder. Patients with BS have photosensitivity, telangiectatic facial erythema, and stunted growth. They...
Bloom syndrome (BS) is a rare autosomal recessive inherited disorder. Patients with BS have photosensitivity, telangiectatic facial erythema, and stunted growth. They usually have mild microcephaly, and distinctive facial features such as a narrow, slender face, micrognathism, and a prominent nose. Kostmann disease (KD) is a subgroup of severe congenital neutropenias. The diagnosis of severe congenital neutropenia is based on clinical symptoms, bone marrow findings, and genetic mutation. Here, we report a female patient with a triangular face, nasal prominence, and protruding ears presenting with recurrent infections and severe neutropenia. Molecular genetic testing revealed a compound heterozygous variant in the HCLS-1-associated protein X-1 gene [(c.130_131insA) p.(trp44*), c.430 dup(p.Val144fs)] and a new homozygous variant in Bloom Syndrome RecQ like helicase gene [c.2074+2T>C p.(?)]. She was diagnosed with both BS and KD. To the best of our knowledge, this is the first case of coexisting BS and KD in a patient ever reported.
Topics: Humans; Female; Bloom Syndrome; Congenital Bone Marrow Failure Syndromes; Neutropenia; Mutation
PubMed: 38113221
DOI: 10.1097/MPH.0000000000002798 -
Clinical Genetics Apr 2024Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra-rare skeletal dysplasia caused by heterozygous intragenic RUNX2... (Review)
Review
Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra-rare skeletal dysplasia caused by heterozygous intragenic RUNX2 duplications, comprising either exons 3 to 5 or exons 3 to 6 of RUNX2. In this study, we describe a 14-year-old Belgian boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly. Clinical and radiographic examination revealed mild facial dysmorphism, dental anomalies, enlarged clavicles, genua valga and metaphyseal flaring and thin cortices with an osteoporotic skeletal appearance. Exome sequencing led to the identification of a de novo heterozygous tandem duplication within RUNX2, encompassing exons 3 to 7. This duplication is larger than the ones previously reported in MDMHB cases since it extends into the C-terminal activation domain of RUNX2. We review previously reported cases with MDMHB and highlight the resemblance of this disorder with Pyle disease, which may be explained by intersecting molecular pathways between RUNX2 and sFRP4. This study expands our knowledge on the genotypic and phenotypic characteristics of MDMHB and the role of RUNX2 in rare bone disorders.
Topics: Male; Humans; Adolescent; Brachydactyly; Core Binding Factor Alpha 1 Subunit; Osteochondrodysplasias; Micrognathism; Cleidocranial Dysplasia; Proto-Oncogene Proteins
PubMed: 38108099
DOI: 10.1111/cge.14474 -
Paediatric Anaesthesia Mar 2024Micrognathic neonates are at risk for upper airway obstruction, and many require intubation in the delivery room. Ex-utero intrapartum treatment is one technique for... (Observational Study)
Observational Study
INTRODUCTION
Micrognathic neonates are at risk for upper airway obstruction, and many require intubation in the delivery room. Ex-utero intrapartum treatment is one technique for managing airway obstruction but poses substantial maternal risks. Procedure requiring a second team in the operating room is an alternative approach to secure the obstructed airway while minimizing maternal risk. The aim of this study was to describe the patient characteristics, airway management, and outcomes for micrognathic neonates and their mothers undergoing a procedure requiring a second team in the operating room at a single quaternary care children's hospital.
METHODS
This was a retrospective descriptive study. Subjects had prenatally diagnosed micrognathia and underwent procedure requiring a second team in the operating room between 2009 and 2021. Collected data included infant characteristics, delivery room airway management, critical events, and medications. Follow-up data included genetic testing and subsequent procedures within 90 days. Maternal data included type of anesthetic, blood loss, and incidence of transfusion.
RESULTS
Fourteen deliveries were performed via procedure requiring a second team in the operating room during the study period. 85.7% were male, and 50% had a genetic syndrome. Spontaneous respiratory efforts were observed in 93%. Twelve patients (85.7%) required an endotracheal tube or tracheostomy. Management approaches varied. Medications were primarily a combination of atropine, ketamine, and dexmedetomidine. Oxygen desaturation was common, and three patients experienced bradycardia. There were no periprocedural deaths. Follow-up at 90 days revealed that 78% of patients underwent at least one additional procedure, and one patient died due to an unrelated cause. All mothers underwent cesarean deliveries under neuraxial anesthesia. Median blood loss was 700 mL [IQR 700 mL, 800 mL]. Only one mother required a blood transfusion for pre-procedural placental abruption.
DISCUSSION
Procedure requiring a second team in the operating room is a safe and effective approach to manage airway obstruction in micrognathic neonates while minimizing maternal morbidity.
CONCLUSIONS
Though shown to be safe and effective, more data are needed to support the use of procedure requiring a second team in the operating room as an alternative to ex-utero intrapartum treatment for micrognathia outside of highly specialized maternal-fetal centers.
Topics: Infant, Newborn; Infant; Child; Humans; Male; Female; Pregnancy; Micrognathism; Retrospective Studies; Placenta; Airway Management; Airway Obstruction
PubMed: 38069629
DOI: 10.1111/pan.14806 -
Prenatal Diagnosis Dec 2023Trio exome sequencing was performed on a fetus with bilateral mesomelia of the lower limbs with significant angulation of the tibial bones, micrognathia and...
A novel SMOC1 pathogenic homozygous variant in a fetus with mesomelia of the lower limbs, micrognathia and hypertelorism and an incidental finding of CYP21A2-related congenital adrenal hyperplasia.
Trio exome sequencing was performed on a fetus with bilateral mesomelia of the lower limbs with significant angulation of the tibial bones, micrognathia and hypertelorism detected on ultrasound scan at 19 + 0 weeks gestation. The couple is consanguineous. A homozygous pathogenic frameshift variant in the SMOC1 gene (c.339_340del p.(Phe114Cysfs*40)) was detected and both parents were shown to be heterozygous. Pathogenic variants in the SMOC1 gene are associated with microphthalmia with limb anomalies which multidisciplinary team discussion determined to be causal of the scan anomalies detected. The fetus was also a compound heterozygote for CYP21A2 pathogenic variants, confirming a second diagnosis of non-classical congenital adrenal hyperplasia, which was felt incidental to the scan findings. The risk that this couple's next pregnancy would be affected by either of these disorders is 1 in 4 (25%) and demonstrates the importance of genetic diagnoses for the family and implications for future pregnancies.
Topics: Pregnancy; Female; Humans; Adrenal Hyperplasia, Congenital; Micrognathism; Hypertelorism; Incidental Findings; Fetal Diseases; Fetus; Lower Extremity; Mutation; Osteonectin; Steroid 21-Hydroxylase
PubMed: 38059661
DOI: 10.1002/pd.6485 -
Stomatologiia 2023A method for diagnosing, planning and surgical treatment of patients with micrognathia of the mandible with physiological occlusion is proposed, which makes it possible...
A method for diagnosing, planning and surgical treatment of patients with micrognathia of the mandible with physiological occlusion is proposed, which makes it possible to objectively assess the severity of the anomaly and concomitant functional disorders of external respiration in the nasopharynx and oropharynx, as well as to identify the pathophysiological mechanisms of obstructive sleep apnea syndrome (OSAS) and develop an optimal surgical treatment plan with high functional and aesthetic results.
Topics: Humans; Micrognathism; Genioplasty; Sleep Apnea, Obstructive; Mandible; Osteogenesis, Distraction
PubMed: 37997313
DOI: 10.17116/stomat202310206148 -
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 -
Bone Feb 2024Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders associated with decreased fetal movement, with a prevalence between 1/3000 and 1/5200 live... (Review)
Review
INTRODUCTION
Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders associated with decreased fetal movement, with a prevalence between 1/3000 and 1/5200 live births. Typical features of AMC include multiple joint contractures present at birth, and can affect all joints of the body, from the jaw, and involving the upper limbs, lower limbs and spine. The jaws may be affected in 25 % of individuals with AMC, with limited jaw movement and mouth opening. Other oral and maxillofacial deformities may be present in AMC, including cleft palate, micrognathia, periodontitis and delayed teething. To our knowledge, oral and maxillofacial abnormalities have not been systematically assessed in individuals with AMC. Therefore, this scoping review was conducted to identify, collect, and describe a comprehensive map of the existing knowledge on dental and maxillofacial involvement in individuals with AMC.
METHODOLOGY
A scoping review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. The PRISMA guidelines for scoping reviews were followed and databases were searched for empirical articles in English and French published until October 2022. We searched MEDLINE, Embase, Web of Science and ERIC databases. Two authors independently reviewed the articles and extracted the data.
RESULTS
Of a total of 997 studies that were identified, 96 met the inclusion criteria and were subsequently included in this scoping review. These 96 studies collectively provided insights into 167 patients who exhibited some form of oral and/or maxillofacial involvement. Notably, 25 % of these patients were within the age range of 0-6 months. It is worth highlighting that only 22 out of the 96 studies (22.9 %), had the primary objective of evaluating dental and/or maxillofacial deformities. Among the patients studied, a prevalent pattern emerged, revealing that severe anomalies such as micrognathia (56 %), high-arched palate (29 %), cleft palate (40 %), limited mouth opening (31 %), and dental anomalies (28 %) were frequently observed. Importantly, many of these patients were found to have more than one of these anomalies. Even though these maxillofacial impairments are known to be associated with dental problems (e.g., cleft palate is associated with oligodontia, hypodontia, and malocclusion), their secondary effects on the dental phenotype were not reported in the studies.
CONCLUSION
Our findings have uncovered a notable deficiency in existing literature concerning dental and maxillofacial manifestations in AMC. This underscores the need for interdisciplinary collaboration and the undertaking of extensive prospective cohort studies focused on AMC. These studies should assess the oral and maxillofacial abnormalities that can impact daily functioning and overall quality of life.
Topics: Infant, Newborn; Humans; Infant; Arthrogryposis; Cleft Palate; Micrognathism; Prospective Studies; Quality of Life
PubMed: 37951521
DOI: 10.1016/j.bone.2023.116955 -
The Journal of Craniofacial SurgeryRobin sequence (RS) is a congenital clinical condition characterized by micrognathia, glossoptosis, and respiratory distress. Conservative methods could be responsible...
INTRODUCTION
Robin sequence (RS) is a congenital clinical condition characterized by micrognathia, glossoptosis, and respiratory distress. Conservative methods could be responsible for releasing feeding and respiratory impairment but little information about mandibular growth is known in long-term follow-up.
OBJECTIVE
Assessing the longitudinal behavior of the facial profile of individuals with isolated RS who underwent conservative micrognathia treatment using photographs during the whole craniofacial growth.
METHODS
Photographs of the right facial profile of 100 patients were used (50 individuals with isolated RS and 50 individuals without craniofacial anomaly). The individuals with RS were evaluated at 3 different times (T1: infant, T2: mixed dentition, T3: permanent dentition) by measuring the facial convexity angle (FCA; G.Sn.Pog´). A comparison between T3 and control group (C), individuals without craniofacial anomalies and in permanent dentition, was also performed, checking the FCA, nasolabial angle (Ls.Sn.Cm), mentolabial fold (Li.Si.Pog´), facial inferior third (Sn.Gn´.C) angles and the ratio between middle anterior facial height and lower anterior facial height.
RESULTS
The T3 group showed an increased angle of facial convexity and increased facial inferior third angle and middle anterior facial height/lower anterior facial height ratio compared with the control group. In the longitudinal evaluation of individuals with isolated RS, significant differences were identified between T1 and T2 groups and T1 and T3 groups showing that the increased facial convexity was higher in the infants and that did not change significantly between the phases of mixed and permanent dentition.
CONCLUSIONS
RS showed increased facial convexity in all phases evaluated, but their convexity decreased with growth. When compared with individuals without craniofacial anomalies, the individuals continue to exhibit retrognathism in the permanent dentition. The lack of a mandible projection has led to a considerable number of orthognathic surgeries for the correction of discrepancies.
Topics: Infant; Humans; Pierre Robin Syndrome; Micrognathism; Cephalometry; Follow-Up Studies; Mandible
PubMed: 37934950
DOI: 10.1097/SCS.0000000000009749 -
Clinical Oral Investigations Dec 2023The purpose of this study was to evaluate the 3D anatomical features of unilateral (UCLP) and bilateral (BCLP) complete cleft lip and palate with those of skeletal Class...
OBJECTIVE
The purpose of this study was to evaluate the 3D anatomical features of unilateral (UCLP) and bilateral (BCLP) complete cleft lip and palate with those of skeletal Class III dentofacial deformities.
MATERIALS AND METHODS
In total, 92 patients were divided into cleft and noncleft groups. The cleft group comprised 29 patients with UCLP and 17 patients with BCLP. The noncleft group comprised 46 patients with Class III dentofacial deformities. 3D anatomical landmarks were identified and the corresponding measurements were made on the cone-beam computed tomography (CBCT).
RESULTS
The differences between the affected and unaffected sides of the patients with UCLP were nonsignificant. The differences between the patients with UCLP and BCLP were nonsignificant except for the SNA angle. Significant differences between the patients with clefts and Class III malocclusion were identified for the SNA, A-N perpendicular, and A-N Pog line, indicating that the maxillae of the patients in the cleft group were more retrognathic and micrognathic. Relative to the noncleft group patients, the cleft group patients had a significantly smaller ramus height.
CONCLUSION
The affected and unaffected sides of the patients with UCLP did not exhibit significant differences. The maxillae of the patients with UCLP were significantly more retrognathic than those of the patients with BCLP. The maxillae and mandibles of the patients in the cleft group were more micrognathic and retropositioned relative to those of the noncleft Class III patients.
CLINICAL RELEVANCE
The maxillary and mandibular findings indicated greater deficiencies in the patients with UCLP or BCLP than in those with skeletal Class III malocclusion. Appropriate surgical design should be administered.
Topics: Humans; Cleft Lip; Cleft Palate; Dentofacial Deformities; Malocclusion, Angle Class III
PubMed: 37910241
DOI: 10.1007/s00784-023-05345-z -
NeoReviews Nov 2023
Topics: Pregnancy; Female; Humans; Micrognathism; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 37907406
DOI: 10.1542/neo.24-11-e753