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Molecular Genetics & Genomic Medicine Apr 2024Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain...
BACKGROUND
Mandibulofacial dysostosis with microcephaly (MFDM, OMIM# 610536) is a rare monogenic disease that is caused by a mutation in the elongation factor Tu GTP binding domain containing 2 gene (EFTUD2, OMIM* 603892). It is characterized by mandibulofacial dysplasia, microcephaly, malformed ears, cleft palate, growth and intellectual disability. MFDM can be easily misdiagnosed due to its phenotypic overlap with other craniofacial dysostosis syndromes. The clinical presentation of MFDM is highly variable among patients.
METHODS
A patient with craniofacial anomalies was enrolled and evaluated by a multidisciplinary team. To make a definitive diagnosis, whole-exome sequencing was performed, followed by validation by Sanger sequencing.
RESULTS
The patient presented with extensive facial bone dysostosis, upward slanting palpebral fissures, outer and middle ear malformation, a previously unreported orbit anomaly, and spina bifida occulta. A novel, pathogenic insertion mutation (c.215_216insT: p.Tyr73Valfs*4) in EFTUD2 was identified as the likely cause of the disease.
CONCLUSIONS
We diagnosed this atypical case of MFDM by the detection of a novel pathogenetic mutation in EFTUD2. We also observed previously unreported features. These findings enrich both the genotypic and phenotypic spectrum of MFDM.
Topics: Humans; Microcephaly; Mandibulofacial Dysostosis; Phenotype; Mutation; Intellectual Disability; Peptide Elongation Factors; Ribonucleoprotein, U5 Small Nuclear
PubMed: 38562046
DOI: 10.1002/mgg3.2426 -
Pediatric Neurosurgery 2024The association between trigonocephaly and Sylvian fissure arachnoid cysts (ACs) has been occasionally reported in the literature. However, the real incidence of this...
INTRODUCTION
The association between trigonocephaly and Sylvian fissure arachnoid cysts (ACs) has been occasionally reported in the literature. However, the real incidence of this association and its clinical relevance remain unknown.
METHODS
The authors collected and retrospectively reviewed all clinical charts and CT scans of patients surgically treated for trigonocephaly at the Pediatric Neurosurgical Department of Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS from January 2014 to June 2023.
RESULTS
During the study period, 136 patients with trigonocephaly underwent surgery. Analysis of the clinical charts revealed that in 39.7% of the cases (54/136), preoperative CT scan depicted the presence of a Sylvian fissure AC. Of these, AC was bilateral in 23 cases and unilateral in the remaining 31. All unilateral ACs were on the left side. The ACs were classified as Galassi grade I in 52 cases (96.3%) and Galassi grade II in 2 cases (3.7%). Interestingly, in 1 case we reported a Galassi grade I AC enlargement during follow-up, thereby necessitating surgical fenestration.
CONCLUSION
ACs and trigonocephaly are well-known conditions for pediatric neurosurgeons; however, their association is poorly defined. Despite the lack of reports on the incidence and clinical significance of this association, it is worth knowing that radiological follow-up is essential in monitoring AC evolution.
Topics: Humans; Arachnoid Cysts; Retrospective Studies; Male; Female; Infant; Craniosynostoses; Child, Preschool; Tomography, X-Ray Computed; Child
PubMed: 38531328
DOI: 10.1159/000538559 -
Nagoya Journal of Medical Science Feb 2024The basket-weave method is an orbicularis oris muscle reconstruction method used in primary unilateral cleft lip repair. We compared the long-term results of the...
The basket-weave method is an orbicularis oris muscle reconstruction method used in primary unilateral cleft lip repair. We compared the long-term results of the basket-weave method with those of a conventional method. For primary unilateral cleft lip repair, we compared the long-term results of 7 cases in which the orbicularis oris muscle was reconstructed by use of the basket-weave method, and of 7 cases in which the reconstruction was performed by use of the conventional method. The average postoperative follow-up period was 12 years and 7 months for the basket-weave method, and 11 years and 9 months for the conventional method. Using photographs of the front and elevation angle views, we evaluated the results as good if the philtrum ridge was formed on the fissure side and was almost symmetrical in height; as fair if the philtrum ridge was lower than the normal side; and as poor if the philtrum ridge had disappeared. For the basket-weave method, the results were good in 6 cases (85.7%), fair in 1 case (14.3%), and poor in 0 cases. For the conventional method, the results were good in 2 cases (28.6%), fair in 4 cases (57.1%), and poor in 1 case (14.3%). A significant difference was found between the 2 groups (Mann-Whitney U test, P = 0.0417). The philtrum ridge shape could be reconstructed by use of the basket-weave method, which gave better results in the long-term than did the conventional method for orbicularis oris muscle reconstruction in primary unilateral cleft lip repair.
Topics: Humans; Lip; Cleft Lip; Facial Muscles; Postoperative Period
PubMed: 38505716
DOI: 10.18999/nagjms.86.1.64 -
BMC Medical Genomics Mar 2024Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder.
BACKGROUND
Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder.
METHODS
To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed.
RESULTS
The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5_4342 + 8delGTGA (NM_001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5_4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115_4342del: p.Gly1373_Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant.
CONCLUSIONS
In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions.
Topics: Male; Humans; Child; Mandibulofacial Dysostosis; Mutation; Exons; Introns; China; Nuclear Proteins; Phosphoproteins
PubMed: 38500116
DOI: 10.1186/s12920-024-01828-4 -
Cureus Mar 2024Cerebral infarction due to post-traumatic cerebral vasospasm is rare. Although some modalities are recommended to detect post-traumatic cerebral vasospasm, its diagnosis...
Cerebral infarction due to post-traumatic cerebral vasospasm is rare. Although some modalities are recommended to detect post-traumatic cerebral vasospasm, its diagnosis remains controversial and challenging. Therefore, in this report, we will use a case report to highlight challenges and to delineate the characteristics of post-traumatic cerebral vasospasm in pediatric patients, including the diagnostic and treatment options. A 12-year-old female was admitted to our hospital following a motor vehicle collision. Her consciousness was severely impaired. Initial computed tomography (CT) revealed an acute subdural hematoma along the tentorium, and a focal subarachnoid hemorrhage was observed in the Sylvian fissure. The patient underwent the insertion of an intracranial pressure sensor and received therapy for increased intracranial pressure (ICP) control under sedation. On the second day, CT angiography (CTA) revealed no signs of arterial abnormality. A patient who is comatose or under sedation has masked neurological symptoms. Thus, new neurological events could only be detected via an intracranial pressure sensor. Her ICP increased on the seventh day, and a CT scan showed a new cerebral infarction in the right middle cerebral artery (MCA) region. We performed decompressive craniectomy to reduce ICP. Postoperative CTA confirmed severe vasospasm in the right MCA. The severe cerebral vasospasm induced the cerebral infarction. Our review suggests that physicians in trauma departments should frequently perform vascular evaluations by CTA, magnetic resonance angiography (MRA), transcranial Doppler ultrasound, or digital subtraction angiography (DSA), especially within two weeks from onset, to detect post-traumatic cerebral vasospasm.
PubMed: 38495962
DOI: 10.7759/cureus.56275 -
International Medical Case Reports... 2024Coloboma means curtailed in Greek language. It is mainly used when normal tissue of the eye or another organ is not present since birth. Coloboma is a congenital...
BACKGROUND
Coloboma means curtailed in Greek language. It is mainly used when normal tissue of the eye or another organ is not present since birth. Coloboma is a congenital abnormality mainly caused by incomplete closure of the embryonic fissure of the choroid part of eye.
PURPOSE
The aim of this case report is to share the clinical findings in a patient with bilateral iris coloboma, low vision, and headache.
PATIENTS AND METHODS
Case report.
RESULTS
An eleven-year-old boy with low vision and headache visited the University Eye Hospital of Kabul University of Medical Science (UEHKUMS) for consultation. Ophthalmic examination revealed a bilateral iris coloboma without concomitant chorioretinal defect, refractive error, and high intraocular pressure in both eyes. The refractive error of the patient was corrected by advising proper glasses, and the high intraocular pressure was controlled by anti-glaucoma drops. After several follow-up visits, the patient no longer complained of headache and low vision.
CONCLUSION
Visiting patients with iris coloboma should be considered for intraocular pressure (IOP) check, and screening of other family members is mandatory.
PubMed: 38495805
DOI: 10.2147/IMCRJ.S453954 -
Narra J Dec 2023Harlequin ichthyosis is a severe and fatal presentation of ichthyosis with an autosomal recessive inheritance. Infants with Harlequin ichthyosis have a high mortality...
Harlequin ichthyosis is a severe and fatal presentation of ichthyosis with an autosomal recessive inheritance. Infants with Harlequin ichthyosis have a high mortality rate, and a dismal prognosis; therefore the majority of neonates die shortly after birth from infection, heat loss, dehydration, electrolytic imbalances, or respiratory distress. The aim of this case report was to present a fatal case of Harlequin ichthyosis with no family history of any inherited skin disorder. A 3-day-old baby was presented to the emergency room with congenital abnormalities at birth, fissured hyperkeratotic skin, and thick yellow plates of scales. The parents had no history of consanguineous marriage, no relevant past medical history, and no family history of the same condition. The patient was unwell, pulse 162 times/minute, respiratory rate 48 times/minute, and axillary temperature 36.9oC. APGAR score was 8 in the 1st minute and 9 in the 5th minute. Based on the typical clinical appearance, the patient was diagnosed with Harlequin ichthyosis. Due to a lack of facility, a mutation analysis was not carried out. The patient was then transferred to the neonatal intensive care unit (NICU) and treated in a humidified incubator and medicated with intravenous antibiotics (ampicillin sulbactam 125 mg/12 hour and gentamicin 13 mg/24 hour), topically fusidic acid and mild emollients. A central venous catheter was used for intravenous access. The poor prognosis resulted in the patient dying at the age of 5-day-old. This case highlights that prenatal diagnosis is critical for early detection and disease prevention. Mutation screening for the gene is suggested for consanguinity marriages and with a history of ichthyosis.
PubMed: 38455615
DOI: 10.52225/narra.v3i3.302 -
Cureus Feb 2024We present an interesting case of mediastinal small cell carcinoma (MSCC), an exceedingly rare entity, comorbid with idiopathic pulmonary fibrosis (IPF). A 66-year-old...
We present an interesting case of mediastinal small cell carcinoma (MSCC), an exceedingly rare entity, comorbid with idiopathic pulmonary fibrosis (IPF). A 66-year-old female was first seen in the pulmonology office for abnormal chest computed tomography (CT) findings of right apical bronchiectasis and subpleural fibrotic changes with focal pleural thickening along the fissures, along with a right lower lobe nodule. Pulmonary function testing (PFT) showed an obstructive pattern with modest bronchodilator response, although subsequent PFT showed a worsening restrictive pattern with a worsening DLCO. On a follow-up CT one year later, a soft tissue density with peripheral calcification was found in the anterior mediastinum, later found to be hypermetabolic on a PET scan. Radiographically, fibrosis worsened with the appearance of worsening diffuse bilateral coarse reticular interstitial changes with lower lobe predominance, honeycombing, and areas of ground-glass opacity. A biopsy of the mediastinal lesion showed a high-grade neuroendocrine tumor. Cam5.2, insulinoma-associated protein-1, synaptophysin, and thyroid transcription factor-1 immunostains were positive. She underwent four cycles of chemotherapy with cisplatin and etoposide with a total of 60 Gy of radiation. Mediastinal mass started to decrease in size. Her respiratory status, imaging, and PFTs continued to show evidence of IPF progression. Prednisone resulted in modest clinical and radiographic response. Steroid-sparing therapy with mycophenolate mofetil, although effective, had to be discontinued due to GI bleeding. Anti-fibrotic therapy was deferred due to evidence showing a lack of clinical improvement. We discuss the existing evidence available on IPF management and proceed to highlight the deficiencies in existing data available on the management of IPF and MSCC in these patients. Most of the cases of MSCC reported in the past have managed MSCC using guidance from treatment practices for small cell lung cancer. No reported cases discuss or describe the management of IPF and MSCC in the very rare cohort of patients our case represents.
PubMed: 38449967
DOI: 10.7759/cureus.53578 -
Anatomy & Cell Biology Mar 2024Transverse basilar cleft (TBC) is an extremely rare variation of the clivus or the basilar part of the occipital bone. In this report, a unilateral transverse basilar...
Transverse basilar cleft (TBC) is an extremely rare variation of the clivus or the basilar part of the occipital bone. In this report, a unilateral transverse basilar fissure was found at the clivus in a head computed tomography of an 18-year-old female patient diagnosed with hemifacial microsomia (HFM). Image analysis of this patient showed shortening of the ramus of the right mandible along with medial displacement of the right temporomandibular joint and hypoplastic right maxilla. In addition, observation of the clivus showed a cleft between the basioticum and basioccipital bones at the level of the pharyngeal tubercle on the right side. This cleft was identified as TBC. Clival variations, TBC included, attributed to HFM have never been reported. This report draws attention to the complex relationship between abnormal development of clivus and HFM syndrome, and sheds light on a possible genetic and molecular association between these two conditions.
PubMed: 38449077
DOI: 10.5115/acb.23.289 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Mar 2024To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104). (Review)
Review
OBJECTIVE
To explore the clinical phenotype and genetic etiology of a child with Developmental epileptic encephalopathy type 104 (DEE 104).
METHODS
A child who had presented at the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in February 2021 for recurrent seizures over 1 month was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.
RESULTS
The child, a five-month-old male, had presented with frequent focal seizures with severe developmental retardation from infancy. Physical examination showed emaciation, microcephaly, oblique palpebral fissures, Stahl's ears, and hypotonia in the limbs. Electroencephalogram revealed multi-focal sharp waves, slow waves and slow spinal waves. Cranial magnetic resonance imaging revealed enlargement of bilateral lateral ventricles and the third ventricle, along with widening of brain sulci, fissure and cisterna. WES revealed that he had harbored a heterozygous c.2401C>T (p.His801Tyr) missense variant of the ATP6V0A1 gene. Sanger sequencing showed that both of his parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+PM2_Supporting+PP3). The proband was diagnosed with DEE 104. Early treatment with sodium valproate has failed, but the child had become seizure free after the addition of levetiracetam and topiramate. He still had abnormal EEG discharges and severe psychomotor retardation. Combining our case and a review of literature, DEE104 is mainly caused by de novo heterozygous variants of the ATP6V0A1 gene with an autosomal dominant inheritance. The patients may show refractory epilepsy and severe global developmental delay from infancy.
CONCLUSION
The c.2401C>T (p.His801Tyr) variant probably underlay the DEE104 in this child.
Topics: Humans; Infant; Male; Brain; Drug Resistant Epilepsy; Electroencephalography; Epilepsy, Generalized; Microcephaly; Vacuolar Proton-Translocating ATPases
PubMed: 38448027
DOI: 10.3760/cma.j.cn511374-20221221-00881