-
Wounds : a Compendium of Clinical... Mar 2023Dubowitz syndrome is a rare genetic disease with only a few cases reported in the literature. It is characterized by growth retardation, microcephaly, facial dysmorphism...
INTRODUCTION
Dubowitz syndrome is a rare genetic disease with only a few cases reported in the literature. It is characterized by growth retardation, microcephaly, facial dysmorphism and higher risk of developing cancer and cardiomyopathies. PG is an autoinflammatory disorder that causes painful ulcers to develop on the skin and has not been previously associated with Dubowitz syndrome.
CASE PRESENTATION
The authors report the case of a 50-year-old female with Dubowitz syndrome who developed painful ulcerative lesions. An incisional biopsy was performed to rule out other diagnoses, and a subsequent clinical diagnosis of PG was made. The patient was treated with specialized wound dressings and oral glucocorticoids. The clinical picture improved consistently after 7 weeks of therapy.
CONCLUSIONS
This case report, to the authors' knowledge, is the first to suggest a possible association between Dubowitz syndrome and PG and also to indicate an effective treatment.
Topics: Female; Humans; Middle Aged; Comorbidity; Growth Disorders; Microcephaly; Pyoderma Gangrenosum; Facies; Intellectual Disability; Ulcer; Glucocorticoids
PubMed: 37023352
DOI: 10.25270/wnds/22051 -
Molecular Genetics & Genomic Medicine May 2021Dubowitz syndrome (DS) is a complex and rare condition characterized by postnatal growth retardation, microcephaly, short stature, mild developmental delay, facial...
BACKGROUND
Dubowitz syndrome (DS) is a complex and rare condition characterized by postnatal growth retardation, microcephaly, short stature, mild developmental delay, facial dysmorphism, skin eruption and bone marrow failure. Though approximately 200 cases have been described so far, no specific genetic analysis, laboratory tests or radiological exams are available to confirm the diagnosis which is still based on clinical and facial features. Although short stature is a major feature of the syndrome, no endocrine alterations have been reported so far and scant data are available about the efficacy and safety of GH treatment in these patients.
METHODS
A 13-year-old male patient was referred to our attention for short stature. Endocrinological evaluation including GH axis, adrenal and gonadal functions were assessed. aCGH was performed.
RESULTS
14q terminal microdeletion associated with Dubowitz phenotype was found. Endocrinological investigations revealed the presence of hypopituitarism which showed a satisfactory response to short-term growth hormone therapy. The subject also started glucocorticoid replacement therapy. Disorders in pubertal progression and gonadal function were noted.
CONCLUSIONS
Dubowitz syndrome (DS) includes different clinical findings variably occurring. Subjects with a Dubowitz phenotype should be carefully monitored for endocrinological anomalies. The prompt recognition of potential life-threatening endocrinological condition for example adrenal insufficiency is mandatory in order to start an adequate and early treatment.
Topics: Chromosome Deletion; Chromosomes, Human, Pair 14; Eczema; Facies; Growth Disorders; Growth Hormone; Hormone Replacement Therapy; Humans; Intellectual Disability; Male; Microcephaly; Phenotype; Young Adult
PubMed: 33788412
DOI: 10.1002/mgg3.1644 -
Journal of Cerebrovascular and... Mar 2020Cerebral cavernous malformations (CCMs) are proliferative sinusoidal vascular lesions and are the most common vascular malformations of the brain. They can occur...
Cerebral cavernous malformations (CCMs) are proliferative sinusoidal vascular lesions and are the most common vascular malformations of the brain. They can occur sporadically or secondary to an underlying genetic predisposition where multiple lesions are commonly seen. Dubowitz syndrome is a clinically-diagnosed rare genetic disorder with an unknown molecular basis. An association between these conditions has not been reported previously. A 30-year-old woman with a Dubowitz-like syndrome presented with acute left leg weakness, gait ataxia and transient loss of consciousness. Imaging revealed five CCMs with recent hemorrhage in relation to one lesion in the left middle cerebellar peduncle. A recurrent hemorrhage from the same lesion occurred ten weeks later and she underwent microsurgical excision of this malformation. Genetic analysis revealed an unbalanced chromosomal rearrangement involving partial deletion of chromosome 7q21, the locus of the CCM1/KRIT1 gene known to be associated with familial CCMs. This is the first description of CCMs in association with the Dubowitz phenotype. The genetic basis of Dubowitz syndrome may be heterogeneous but, for the first time, overlap is demonstrated between this condition and multiple CCMs, with a possible common genetic etiology. Knowledge of this association may be of help in the management of acute neurological presentations in Dubowitz-like syndromes. Keywords: Hemangioma, Cavernous, Central nervous system, Dubowitz syndrome, Genetics.
PubMed: 32596139
DOI: 10.7461/jcen.2020.22.1.15 -
Case Reports in Dentistry 2022Oligodontia is a dental abnormality in which the patient is missing teeth. It is a hereditary disorder characterized by agenesis of more than six primary or permanent...
INTRODUCTION
Oligodontia is a dental abnormality in which the patient is missing teeth. It is a hereditary disorder characterized by agenesis of more than six primary or permanent teeth, excluding the wisdom teeth. Oligodontia is often related with an abnormal size of teeth, conical shape, taurodontism, frequent enamel abnormalities, and delayed eruption. Oligodontia may be clinically isolated or associated with ectodermal dysplasia, a large group of rare diseases, and other syndromes. Dental characteristics of a six-and-a-half-year-old Moroccan boy with oligodontia and in apparent good health were described. Three syndromes associated with oligodontia have been discussed. Above all, based on the facial phenotype, Dubowitz syndrome has been retained as the most likely diagnostic hypothesis. This case could be the first reported case described in Morocco, but a thorough examination with genetic analysis must be carried out.
CONCLUSION
Oligodontia could clinically be isolated or associated with ectodermal dysplasia, a large group of rare diseases, and other syndromes.
PubMed: 36601644
DOI: 10.1155/2022/1045327 -
Journal of Human Genetics Apr 2017Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology,...
Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay allowed us to make a diagnosis of KOS. In conclusion, our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.
Topics: Abnormalities, Multiple; Adult; Carrier Proteins; Child; Child, Preschool; Diagnosis, Differential; Eczema; Eye Abnormalities; Face; Facies; Female; GTPase-Activating Proteins; Growth Disorders; Hand Deformities, Congenital; Humans; Intellectual Disability; Karyotype; Limb Deformities, Congenital; Male; Membrane Proteins; Microcephaly; Micrognathism; Mutation; Neck; Nerve Tissue Proteins; Pathology, Molecular; Sequence Analysis, DNA; Ubiquitin-Protein Ligases
PubMed: 28003643
DOI: 10.1038/jhg.2016.151 -
Nucleic Acids Research Sep 2019Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs...
Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs and 11 mRNAs and their post-transcriptional modification constitutes one of the key regulatory steps during mitochondrial gene expression. Cytosine-5 methylation (m5C) has been detected in mitochondrial transcriptome, however its biogenesis has not been investigated in details. Mammalian NOP2/Sun RNA Methyltransferase Family Member 2 (NSUN2) has been characterized as an RNA methyltransferase introducing m5C in nuclear-encoded tRNAs, mRNAs and microRNAs and associated with cell proliferation and differentiation, with pathogenic variants in NSUN2 being linked to neurodevelopmental disorders. Here we employ spatially restricted proximity labelling and immunodetection to demonstrate that NSUN2 is imported into the matrix of mammalian mitochondria. Using three genetic models for NSUN2 inactivation-knockout mice, patient-derived fibroblasts and CRISPR/Cas9 knockout in human cells-we show that NSUN2 is necessary for the generation of m5C at positions 48, 49 and 50 of several mammalian mitochondrial tRNAs. Finally, we show that inactivation of NSUN2 does not have a profound effect on mitochondrial tRNA stability and oxidative phosphorylation in differentiated cells. We discuss the importance of the newly discovered function of NSUN2 in the context of human disease.
Topics: 5-Methylcytosine; Animals; CRISPR-Cas Systems; Eczema; Facies; Fibroblasts; Gene Editing; Gene Knockout Techniques; Growth Disorders; HEK293 Cells; Humans; Intellectual Disability; Methylation; Methyltransferases; Mice; Mice, Knockout; Microcephaly; Mitochondria; Nucleic Acid Conformation; Oxidative Phosphorylation; Primary Cell Culture; Protein Transport; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Mitochondrial; RNA, Transfer
PubMed: 31276587
DOI: 10.1093/nar/gkz559 -
The Tokai Journal of Experimental and... Jul 2011Dubowitz syndrome was first described in 1965 by the English physician Dr. Victor Dubowitz. This genetic disorder causes growth retardation both before and after birth....
Dubowitz syndrome was first described in 1965 by the English physician Dr. Victor Dubowitz. This genetic disorder causes growth retardation both before and after birth. It is primarily diagnosed through the distinctive facial features of affected individuals, including a small triangular-shaped face with a high forehead and wide-set, slitted eyes. The main method of diagnosis is through identification of facial phenotype. Esophageal mass biopsy revealed squamous cell carcinoma type. Both malignancy and IgA deficiency have been reported literature in patients with Dubowitz syndrome. However, Esophagus cancer has not been reported among the malignant tumors. Herein, we reported a patient with Dubowitz syndrome, IgA deficiency and Esophagus cancer.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Eczema; Esophageal Neoplasms; Facies; Fatal Outcome; Growth Disorders; Humans; IgA Deficiency; Intellectual Disability; Male; Microcephaly; Young Adult
PubMed: 21769769
DOI: No ID Found -
Korean Journal of Anesthesiology May 2010Dubowitz syndrome is a rare autosomal recessive disorder that leads to growth retardation (intrauterine, postnatal), mental retardation, a peculiar face, microcephaly,...
Dubowitz syndrome is a rare autosomal recessive disorder that leads to growth retardation (intrauterine, postnatal), mental retardation, a peculiar face, microcephaly, behavioral problems and eczema. The peculiar face of individuals with Dubowitz syndrome includes sparse hair and eyebrows, low-set ears, blepharophimosis, bilateral ptosis, a flat nasal bridge with a broad nasal root and micrognathia. Airway management of such individuals might be difficult due to craniofacial anomalies, such as micrognathia, cleft palate, tooth problems and craniocervical anomalies. In addition, anesthetic management may be complicated by other systemic illnesses. We report the uneventful anesthetic management of a 16-year-old girl with Dubowitz syndrome who underwent a total abdominal hysterectomy after a pelvic examination under general anesthesia. We report this case of Dubowitz syndrome with a review of the relevant literature.
PubMed: 20532061
DOI: 10.4097/kjae.2010.58.5.495 -
The Journal of Clinical Pediatric... 2012Dubowitz syndrome is a rare genetic condition characterized by microcephaly, dysmorphic facial features and delayed general growth. It is transmitted through autosomal...
Dubowitz syndrome is a rare genetic condition characterized by microcephaly, dysmorphic facial features and delayed general growth. It is transmitted through autosomal recessive inheritance. The purpose of this report is to describe the oral, craniofacial and systemic characteristics of a 7-year 11-month-old boy with Dubowitz syndrome and the dental management provided. The pediatric dentist should possess the ability to recognize this rare alteration, to provide dental treatment and to refer for the necessary medical and multidisciplinary treatment.
Topics: Airway Obstruction; Cephalometry; Child; Dental Caries; Dental Restoration, Permanent; Eczema; Facial Bones; Facies; Growth Disorders; Humans; Hypertelorism; Intellectual Disability; Male; Malocclusion; Microcephaly; Micrognathism; Open Bite; Pit and Fissure Sealants; Retrognathia; Syndrome
PubMed: 23534331
DOI: 10.17796/jcpd.37.2.y5w316j142314073 -
PloS One 2013Dubowitz Syndrome is an autosomal recessive disorder with a unique set of clinical features including microcephaly and susceptibility to tumor formation. Although more...
Dubowitz Syndrome is an autosomal recessive disorder with a unique set of clinical features including microcephaly and susceptibility to tumor formation. Although more than 140 cases of Dubowitz syndrome have been reported since 1965, the genetic defects of this disease has not been identified. In this study, we systematically analyzed the DNA damage response and repair capability of fibroblasts established from a Dubowitz Syndrome patient. Dubowitz syndrome fibroblasts are hypersensitive to ionizing radiation, bleomycin, and doxorubicin. However, they have relatively normal sensitivities to mitomycin-C, cisplatin, and camptothecin. Dubowitz syndrome fibroblasts also have normal DNA damage signaling and cell cycle checkpoint activations after DNA damage. These data implicate a defect in repair of DNA double strand break (DSB) likely due to defective non-homologous end joining (NHEJ). We further sequenced several genes involved in NHEJ, and identified a pair of novel compound mutations in the DNA Ligase IV gene. Furthermore, expression of wild type DNA ligase IV completely complement the DNA repair defects in Dubowitz syndrome fibroblasts, suggesting that the DNA ligase IV mutation is solely responsible for the DNA repair defects. These data suggests that at least subset of Dubowitz syndrome can be attributed to DNA ligase IV mutations.
Topics: Adult; Antineoplastic Agents; DNA Breaks, Double-Stranded; DNA Damage; DNA Ligase ATP; DNA Ligases; DNA Repair; Eczema; Facies; Fatal Outcome; Female; Fibroblasts; Gamma Rays; Growth Disorders; Humans; Intellectual Disability; Microcephaly; Mutation; Radiation Tolerance
PubMed: 23372718
DOI: 10.1371/journal.pone.0054389