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Fetal Diagnosis and Therapy 2023Gómez-López-Hernández syndrome (GLHS), also known as cerebello-trigeminal-dermal dysplasia, is an extremely rare neurocutaneous disease, classically described by the...
INTRODUCTION
Gómez-López-Hernández syndrome (GLHS), also known as cerebello-trigeminal-dermal dysplasia, is an extremely rare neurocutaneous disease, classically described by the triad of rhombencephalosynapsis (RES), bilateral focal alopecia, and trigeminal anesthesia. The clinical and radiographic spectrum of GLHS is now known to be broader, including craniofacial and supratentorial anomalies, as well as neurodevelopmental issues.
CASE PRESENTATION
Here, we present a case of antenatally diagnosed GLHS with RES, hydrocephaly, and craniofacial anomalies identified on ultrasound (low-set ears with posterior rotation, hypertelorism, midface hypoplasia, micrognathia, and anteverted nares) which were confirmed by autopsy after termination of pregnancy at 23 weeks of gestation.
DISCUSSION
As no known genetic causes have been identified and the classical triad is not applicable to prenatal imaging, prenatal diagnosis of GLHS is based on neuroimaging and the identification of supporting features. In presence of an RES associated with craniofacial abnormalities in prenatal (brachycephaly, turricephaly, low-set ears, midface retrusion, micrognathia), GLHS should be considered as "possible" according to postnatal criteria.
Topics: Female; Pregnancy; Humans; Micrognathism; Cerebellum; Craniofacial Abnormalities; Alopecia; Prenatal Diagnosis
PubMed: 37062278
DOI: 10.1159/000530643 -
Genetics in Medicine : Official Journal... Jun 2022This study aimed to describe the phenotypic and molecular characteristics of ARCN1-related syndrome.
PURPOSE
This study aimed to describe the phenotypic and molecular characteristics of ARCN1-related syndrome.
METHODS
Patients with ARCN1 variants were identified, and clinician researchers were connected using GeneMatcher and physician referrals. Clinical histories were collected from each patient.
RESULTS
In total, we identified 14 cases of ARCN1-related syndrome, (9 pediatrics, and 5 fetal cases from 3 families). The clinical features these newly identified cases were compared to 6 previously reported cases for a total of 20 cases. Intrauterine growth restriction, micrognathia, and short stature were present in all patients. Other common features included prematurity (11/15, 73.3%), developmental delay (10/14, 71.4%), genitourinary malformations in males (6/8, 75%), and microcephaly (12/15, 80%). Novel features of ARCN1-related syndrome included transient liver dysfunction and specific glycosylation abnormalities during illness, giant cell hepatitis, hepatoblastoma, cataracts, and lethal skeletal manifestations. Developmental delay was seen in 73% of patients, but only 3 patients had intellectual disability, which is less common than previously reported.
CONCLUSION
ARCN1-related syndrome presents with a wide clinical spectrum ranging from a severe embryonic lethal syndrome to a mild syndrome with intrauterine growth restriction, micrognathia, and short stature without intellectual disability. Patients with ARCN1-related syndrome should be monitored for liver dysfunction during illness, cataracts, and hepatoblastoma. Additional research to further define the phenotypic spectrum and possible genotype-phenotype correlations are required.
Topics: Cataract; Child; Dwarfism; Female; Fetal Growth Retardation; Hepatoblastoma; Humans; Intellectual Disability; Liver Neoplasms; Male; Micrognathism; Phenotype; Syndrome
PubMed: 35300924
DOI: 10.1016/j.gim.2022.02.005 -
NeoReviews Nov 2023
Topics: Pregnancy; Female; Humans; Micrognathism; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 37907406
DOI: 10.1542/neo.24-11-e753 -
Epileptic Disorders : International... Dec 2021Coffin-Siris syndrome (CSS) is a rare congenital malformation syndrome, caused by mutations in the ARID1B gene in over half of the cases. While the clinical...
Coffin-Siris syndrome (CSS) is a rare congenital malformation syndrome, caused by mutations in the ARID1B gene in over half of the cases. While the clinical characteristics of the syndrome have been increasingly described, a detailed evaluation of the epileptic phenotype in patients with ARID1B alterations and CSS has not been approached yet. We report seven patients with ARID1B-related CSS, focusing on epilepsy and its electroclinical features. The evolution of epilepsy and EEG findings of children with CSS are described and compared with patients previously reported in the literature. The patients described here reveal common features, consistent with those of patients previously described in the literature. The epilepsy phenotype of CSS due to ARID1B pathogenic variants may be described as focal epilepsy with seizures, variable in frequency, arising from motor areas, with onset in the first years of life and susceptibility to fever, and interictal perisylvian (centrotemporal) epileptiform abnormalities that are enhanced during sleep with possible evolution to an EEG pattern of continuous spike and wave during sleep (without documented developmental regression). Additional information emerging from other patients is needed to confirm this definition.
Topics: Abnormalities, Multiple; DNA-Binding Proteins; Epilepsy; Face; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Neck; Transcription Factors
PubMed: 34730517
DOI: 10.1684/epd.2021.1356 -
International Journal of Gynaecology... Dec 2023Treacher Collins syndrome (TCS) should be suspected if the triad of micrognathia, glossoptosis, and posterior cleft palate, and deformed external ears are observed... (Review)
Review
Treacher Collins syndrome (TCS) should be suspected if the triad of micrognathia, glossoptosis, and posterior cleft palate, and deformed external ears are observed during prenatal ultrasonography, excepting Pierre Robin sequence. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures are conducive to differentiation. Molecular genetics testing can establish a definite diagnosis. A 28-year-old pregnant Chinese woman was referred for systematic ultrasound examination at 24 weeks. Two-dimensional and three-dimensional ultrasound showed polyhydramnios, micrognathia, absence of nasal bone, microtia, secondary cleft palate, mandibular hypoplasia, glossoptosis, and normal limbs and vertebrae. Pierre Robin sequence was misdiagnosed with the triad of micrognathia, glossoptosis, and posterior cleft palate. Final diagnosis of TCS was confirmed by whole-exome sequencing. Visualization of the fetal zygomatic bone and down-slanting palpebral fissures can facilitate a differential diagnosis between Pierre Robin sequence and TCS, with the triad of micrognathia, glossoptosis, and posterior cleft palate.
Topics: Pregnancy; Female; Humans; Adult; Mandibulofacial Dysostosis; Pierre Robin Syndrome; Micrognathism; Glossoptosis; Cleft Palate; Prenatal Diagnosis
PubMed: 37231986
DOI: 10.1002/ijgo.14881 -
European Journal of Dentistry Oct 2021Previous studies showed that noggin gene () sequence alterations, as well as epigenetic factors, could influence mandibular development. The aim of this study was to...
OBJECTIVES
Previous studies showed that noggin gene () sequence alterations, as well as epigenetic factors, could influence mandibular development. The aim of this study was to analyze clinical characteristics, gene sequences, and promoter methylation sites in patients with mandibular micrognathism.
MATERIALS AND METHODS
A total of 35 individuals of five Colombian families were subject to clinical and cephalometric analysis for mandibular micrognathism. One nonaffected individual of each family was included as a control. DNA was isolated from whole blood sample from all individuals by salting out method. Nine gene fragments were amplified by polymerase chain reaction (PCR) and sequenced. Identification of CpG islands for methylation analysis at the gene promoter was performed by MSP-PCR kit (Qiagen R).
STATISTICAL ANALYSIS
A descriptive statistical analysis was carried out evaluating the presence or absence of genetics variants and the methylation sites in the NOG gene.
RESULTS
sequence results of affected individuals with mandibular micrognathism for one of the families studied demonstrated that they were heterozygous for 672 C/A (new mutation). For a second family, individuals were heterozygous for 567 G/C (single nucleotide polymorphism [SNP] RS116716909). For DNA analyzed from all patients studied, no methylations were observed at the gene promoter region.
CONCLUSION
Our results suggested that 672 C/A and 567 G/C variants could be involved in the presence of mandibular micrognathism. Moreover, lack of methylation sites at the gene promoter region of all individuals studied suggests possibly other epigenetic factors could modulate mandibular growth. The search of genetic variants related with mandibular micrognathism will allow to predict in an integral way the development patterns of the patients and therefore establish a better clinical treatment.
PubMed: 34592770
DOI: 10.1055/s-0041-1726162 -
Frontiers in Pediatrics 2023This study will list the most common comorbidities of congenital facial nerve palsy and how to detect and treat them, with special attention for ENT-problems such as...
OBJECTIVES
This study will list the most common comorbidities of congenital facial nerve palsy and how to detect and treat them, with special attention for ENT-problems such as hearing loss. Congenital facial nerve palsy is a very rare entity but in UZ Brussels hospital there was a follow-up of 16 children in the last 30 years.
METHODS
Literature review has been done, combined with thorough research of our own series of 16 children with congenital facial nerve palsy.
RESULTS
Congenital facial nerve palsy can be part of a known syndrome, most commonly Moebius syndrome, but can also appear solely. It appears often bilateral and with a severe gradation. In our series, hearing loss is frequently seen in association with congenital facial nerve palsy. Other abnormalities are dysfunction of the abducens nerve, ophthalmological problems, retro- or micrognathism and abnormalities of limbs or heart. The majority of the children in our series underwent radiological imaging (CT and/or MRI): the facial nerve but also the vestibulocochlear nerve and middle and inner ear can be evaluated.
CONCLUSION
A multidisciplinary approach of congenital facial nerve palsy is recommended as it can affect various bodily functions. Radiological imaging needs to be done to acquire additional information that can be useful for diagnostic and therapeutic purposes. Although congenital facial nerve palsy may not be treatable itself, its comorbidities can be treated and improve the quality of life of the affected child.
PubMed: 36891227
DOI: 10.3389/fped.2023.1077238 -
Human Genetics Jan 2024Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular...
Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.
Topics: Adult; Humans; Child; Intellectual Disability; Abnormalities, Multiple; Micrognathism; Hand Deformities, Congenital; Neck; Phenotype; DNA Helicases; Nuclear Proteins; Transcription Factors; Chromosomal Proteins, Non-Histone; DNA-Binding Proteins; Face
PubMed: 38117302
DOI: 10.1007/s00439-023-02622-5 -
The New England Journal of Medicine Mar 2022
Topics: Humans; Intellectual Disability; Micrognathism; Ribs
PubMed: 35353972
DOI: 10.1056/NEJMc2117812 -
The New England Journal of Medicine Mar 2022
Topics: Humans; Intellectual Disability; Micrognathism; Ribs
PubMed: 35353971
DOI: 10.1056/NEJMc2117812