-
European Journal of Anaesthesiology Aug 2019
PubMed: 31274551
DOI: 10.1097/EJA.0000000000000959 -
Cureus Aug 2023Pyoderma gangrenosum (PG) is a challenging cutaneous manifestation associated with Dubowitz syndrome, a rare genetic disorder characterized by multiple congenital... (Review)
Review
Pyoderma gangrenosum (PG) is a challenging cutaneous manifestation associated with Dubowitz syndrome, a rare genetic disorder characterized by multiple congenital anomalies, developmental delay, and distinctive facial features. This review article aims to provide a comprehensive overview of the association between Dubowitz syndrome and pyoderma gangrenosum, emphasizing the clinical presentation, challenges in diagnosis and management, and potential underlying mechanisms. A comprehensive literature search was conducted to gather relevant studies, and inclusion and exclusion criteria were applied to select appropriate articles. The association between Dubowitz syndrome and pyoderma gangrenosum has been documented in reported cases and studies. Clinical characteristics of Pyoderma gangrenosum in Dubowitz syndrome include painful necrotic ulcers with undermined borders. Diagnosing pyoderma gangrenosum in the context of Dubowitz syndrome can be challenging due to the overlapping clinical features and complexities associated with the syndrome. Managing pyoderma gangrenosum involves a multidisciplinary approach, with general principles of wound care, systemic therapy, and pain management. Specific considerations for treating pyoderma gangrenosum in Dubowitz syndrome include collaboration among specialists and careful monitoring. Future directions for management include further research to understand the underlying mechanisms and develop targeted therapies. Recognizing and addressing pyoderma gangrenosum in Dubowitz syndrome is crucial for optimal patient care. This review enhances awareness among healthcare professionals and provides insights for improving diagnosis, management, and treatment outcomes for individuals with this challenging combination of conditions.
PubMed: 37706150
DOI: 10.7759/cureus.43408 -
Cureus Nov 2023Dubowitz syndrome (DS) is a rare genetic disorder characterized by multiple morphological abnormalities, short stature, and different degrees of mental disability....
Dubowitz syndrome (DS) is a rare genetic disorder characterized by multiple morphological abnormalities, short stature, and different degrees of mental disability. Endocrinological evaluation should be done for these subjects, as they can suffer from multiple hormonal derangements. We present a case of a 12-year-old Lebanese girl, diagnosed with Dubowitz syndrome, who presented to our clinic for short stature. She had received growth hormones (GHs) and improved her height. More investigations showed the presence of Hashimoto thyroiditis with normal thyroid stimulating hormone, so hormonal follow-up was recommended. The association between Dubowitz syndrome and Hashimoto thyroiditis has not been described so far. Thus, in the setting of this syndrome, it is worthwhile to check for growth hormone deficiency and Hashimoto's thyroiditis.
PubMed: 38074036
DOI: 10.7759/cureus.48440 -
American Journal of Medical Genetics.... Jan 2021Dubowitz syndrome (DubS) is considered a recognizable syndrome characterized by a distinctive facial appearance and deficits in growth and development. There have been...
Dubowitz syndrome (DubS) is considered a recognizable syndrome characterized by a distinctive facial appearance and deficits in growth and development. There have been over 200 individuals reported with Dubowitz or a "Dubowitz-like" condition, although no single gene has been implicated as responsible for its cause. We have performed exome (ES) or genome sequencing (GS) for 31 individuals clinically diagnosed with DubS. After genome-wide sequencing, rare variant filtering and computational and Mendelian genomic analyses, a presumptive molecular diagnosis was made in 13/27 (48%) families. The molecular diagnoses included biallelic variants in SKIV2L, SLC35C1, BRCA1, NSUN2; de novo variants in ARID1B, ARID1A, CREBBP, POGZ, TAF1, HDAC8, and copy-number variation at1p36.11(ARID1A), 8q22.2(VPS13B), Xp22, and Xq13(HDAC8). Variants of unknown significance in known disease genes, and also in genes of uncertain significance, were observed in 7/27 (26%) additional families. Only one gene, HDAC8, could explain the phenotype in more than one family (N = 2). All but two of the genomic diagnoses were for genes discovered, or for conditions recognized, since the introduction of next-generation sequencing. Overall, the DubS-like clinical phenotype is associated with extensive locus heterogeneity and the molecular diagnoses made are for emerging clinical conditions sharing characteristic features that overlap the DubS phenotype.
Topics: Adolescent; Child; Child, Preschool; DNA Copy Number Variations; Eczema; Exome; Facies; Female; Genetic Predisposition to Disease; Genome, Human; Genomics; Growth Disorders; Histone Deacetylases; Humans; Infant; Intellectual Disability; Male; Microcephaly; Phenotype; Repressor Proteins; Exome Sequencing
PubMed: 33098347
DOI: 10.1002/ajmg.a.61926 -
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 -
Cureus Jul 2021Dubowitz syndrome is a relatively rare genetic and developmental disorder. An eight-year-old female presented with a complaint of drooping in her left eye since...
Dubowitz syndrome is a relatively rare genetic and developmental disorder. An eight-year-old female presented with a complaint of drooping in her left eye since birth. She had undergone ptosis surgery two years back. There was a history of delayed speech and delayed dentition. She was of moderate built appropriate to her age. There was microcephaly, sparse hair, flat bridge of the nose with a prominent rounded tip, short stature, low-set ears, and micrognathia with subsequent protrusion of upper two incisors. Based on the clinical features a diagnosis of Dubowitz syndrome with left recurrent ptosis was made. She underwent frontalis sling surgery and had a satisfactory outcome.
PubMed: 34422468
DOI: 10.7759/cureus.16436 -
American Journal of Medical Genetics.... Sep 2021Now in its 7th edition, Smith's Recognizable Patterns of Human Malformation was first published in 1970. This 1st edition comprised 135 "dysmorphic syndromes of multiple... (Review)
Review
Now in its 7th edition, Smith's Recognizable Patterns of Human Malformation was first published in 1970. This 1st edition comprised 135 "dysmorphic syndromes of multiple primary defects" and 12 "single syndromic malformations resulting in secondary defects." Of the former, other than a few chromosomal and environmental disorders, most were heritable conditions of then unknown etiology. In 2021, the majority of these conditions are now "solved," a notable exception is Hallermann-Streiff syndrome. The "solved" conditions were typically clinically delineated decades prior to understanding the underlying etiology, which rarely required recent technologies such as exome sequencing (ES) to elucidate. The 7th edition includes nearly 300 syndromes, sequences, and associations. An increasing number of conditions first appearing in the latest editions are sporadic, with many solved using either array CGH or ES. We have reviewed all syndromes that have appeared in "Smith's" with a focus on inheritance, heterogeneity, and year and method of etiologic discovery. Several themes emerge. Genetic heterogeneity and pleiotropy of genes are frequent. Several of the currently "unresolved" syndromes are clinically diverse such as Dubowitz syndrome. Multiple recurrent constellations of embryonic malformations, with VACTERL association as a paradigm, are increasingly likely to have a shared pathogenesis requiring further study.
Topics: Abnormalities, Multiple; Chromosomes, Human; Congenital Abnormalities; Gene-Environment Interaction; Genetic Predisposition to Disease; History, 20th Century; History, 21st Century; Humans
PubMed: 33951288
DOI: 10.1002/ajmg.a.62240 -
Clinical & Experimental Ophthalmology Jul 2021To determine the frequency of isolated blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) versus systemic genetic disorders in patients presenting with...
BACKGROUND
To determine the frequency of isolated blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) versus systemic genetic disorders in patients presenting with blepharophimosis.
METHODS
Retrospective clinical records review. The records of all patients with blepharophimosis seen in the Division of Ophthalmology at the Children's Hospital of Philadelphia during a 12-year-period (2009-2020) were reviewed for medical history, clinical examination findings and results of genetic analyses.
RESULTS
The 135 patients identified with blepharophimosis included 72 females (53%) and 63 males (47%) whose mean ± standard deviation age at first visit was 3.5 ± 6.4 years (range 0-39.8 years). Sixty-seven of the patients (50%) had undergone genetic testing for FOXL2 gene mutation. Fifty-four (81%) harboured FOXL2 gene mutations and 13 (19%) did not. Altogether, 126 patients (93%) had a final diagnosis of isolated BPES. The remaining nine (7%) had syndromic diagnoses ("blepharophimosis-plus"), including Dubowitz syndrome (n = 2), Ohdo syndrome (n = 1), 22q11.2 duplication (n = 1) and 3q22 deletion (n = 2). Three patients with multiple congenital anomalies remain undiagnosed.
CONCLUSIONS
Blepharophimosis is an eyelid feature occurring most commonly in isolation due to FOXL2 gene mutation, but can also be a harbinger of multisystem disease not exclusive to isolated BPES, as observed in 7% of cases in this series. The ophthalmologist is often the first to recognise these unique features, and must consider and rule out non-BPES syndromes before establishing a diagnosed classic BPES. A comprehensive genetic evaluation is, therefore, indicated in all cases.
Topics: Adolescent; Adult; Blepharophimosis; Child; Child, Preschool; Female; Forkhead Box Protein L2; Forkhead Transcription Factors; Humans; Infant; Infant, Newborn; Male; Mutation; Pedigree; Phenotype; Retrospective Studies; Syndrome; Young Adult
PubMed: 33882191
DOI: 10.1111/ceo.13933 -
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 -
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