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Human Mutation May 2020Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioral abnormalities, and seizures....
Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioral abnormalities, and seizures. Only 11 affected individuals have been reported to date, and the phenotype associated with pathogenic variants in this gene have not been fully defined. Here, we present 16 additional patients with predicted pathogenic heterozygous variants in including four individuals from the same family, to further delineate and expand the genotypic and phenotypic spectrum of ZMYND11-related syndromic intellectual disability. The associated phenotype includes developmental delay, particularly affecting speech, mild-moderate intellectual disability, significant behavioral abnormalities, seizures, and hypotonia. There are subtle shared dysmorphic features, including prominent eyelashes and eyebrows, a depressed nasal bridge with bulbous nasal tip, anteverted nares, thin vermilion of the upper lip, and wide mouth. Novel features include brachydactyly and tooth enamel hypoplasia. Most identified variants are likely to result in premature truncation and/or nonsense-mediated decay. Two ZMYND11 variants located in the final exon-p.(Gln586*) (likely escaping nonsense-mediated decay) and p.(Cys574Arg)-are predicted to disrupt the MYND-type zinc-finger motif and likely interfere with binding to its interaction partners. Hence, the homogeneous phenotype likely results from a common mechanism of loss-of-function.
Topics: Alleles; Cell Cycle Proteins; Child; Child, Preschool; Co-Repressor Proteins; DNA-Binding Proteins; Facies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Haploinsufficiency; Humans; Intellectual Disability; Male; Mutation; Nonsense Mediated mRNA Decay; Phenotype; Syndrome; Zinc Fingers
PubMed: 32097528
DOI: 10.1002/humu.24001 -
Genes Feb 20232q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is... (Review)
Review
UNLABELLED
2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type E, short stature, obesity, hypotonia in infancy, and abnormal behavior with autism spectrum disorder. Although numerous cases have been described so far, the exact mapping of the genotype and phenotype have not yet been achieved.
MATERIALS AND METHODS
In this study we analyzed nine newly diagnosed cases with 2q37 deletion (3 male/6 female, aged between 2 and 30 years old), and followed up at the Iasi Regional Medical Genetics Centre. All patients were tested first with MLPA using combined kits P036/P070 subtelomeric screening mix and follow-up mix P264; after, the deletion size and location were confirmed via CGH-array. We compared our findings with the data of other cases reported in the literature.
RESULTS
From nine cases, four had pure 2q37 deletions of variable sizes, and five presented deletion/duplication rearrangements (with chromosomes 2q, 9q, and 11p). In most cases, characteristic phenotypic aspects were observed: 9/9 facial dysmorphism, 8/9 global developmental delay and ID, 6/9 hypotonia, 5/9 behavior disorders, and 8/9 skeletal anomalies-especially brachydactyly type E. Two cases had obesity, one case had craniosynostosis, and four had heart defects. Other features found in our cases included translucent skin and telangiectasias (6/9), and a hump of fat on the upper thorax (5/9).
CONCLUSIONS
Our study enriches the literature data by describing new clinical features associated with 2q37 deletion, and possible genotype-phenotype correlations.
Topics: Humans; Male; Female; Brachydactyly; Autism Spectrum Disorder; Muscle Hypotonia; Genetic Association Studies; Intellectual Disability; Obesity
PubMed: 36833393
DOI: 10.3390/genes14020465 -
Hand (New York, N.Y.) Sep 2016Symbrachydactyly is a unilateral congenital hand malformation characterized by failure of formation of fingers and the presence of rudimentary digit nubbins. The... (Review)
Review
Symbrachydactyly is a unilateral congenital hand malformation characterized by failure of formation of fingers and the presence of rudimentary digit nubbins. The management is variable and are investigated in this review. A detailed review of the literature was compiled into succinct clinically relevant categories. Etiology, classification, non-surgical management, surgical intervention, and patient oriented outcomes are discussed. All interventions should prioritize realistic, evidence-supported appearance and functional gains. Studies of the baseline function and quality of life of children with symbrachydactyly would allow surgeons to better understand functional changes associated with various interventions and would help surgeons and parents to make the best treatment decisions.
Topics: Brachydactyly; Fingers; Humans; Photography; Quality of Life; Treatment Outcome
PubMed: 27698626
DOI: 10.1177/1558944715614857 -
Orphanet Journal of Rare Diseases Jun 2008Brachydactyly ("short digits") is a general term that refers to disproportionately short fingers and toes, and forms part of the group of limb malformations... (Review)
Review
Brachydactyly ("short digits") is a general term that refers to disproportionately short fingers and toes, and forms part of the group of limb malformations characterized by bone dysostosis. The various types of isolated brachydactyly are rare, except for types A3 and D. Brachydactyly can occur either as an isolated malformation or as a part of a complex malformation syndrome. To date, many different forms of brachydactyly have been identified. Some forms also result in short stature. In isolated brachydactyly, subtle changes elsewhere may be present. Brachydactyly may also be accompanied by other hand malformations, such as syndactyly, polydactyly, reduction defects, or symphalangism. For the majority of isolated brachydactylies and some syndromic forms of brachydactyly, the causative gene defect has been identified. In isolated brachydactyly, the inheritance is mostly autosomal dominant with variable expressivity and penetrtance. Diagnosis is clinical, anthropometric and radiological. Prenatal diagnosis is usually not indicated for isolated forms of brachydactyly, but may be appropriate in syndromic forms. Molecular studies of chorionic villus samples at 11 weeks of gestation and by amniocentesis after the 14th week of gestation can provide antenatal diagnosis if the causative mutation in the family is known. The nature of genetic counseling depends both on the pattern of inheritance of the type of brachydactyly present in the family and on the presence or absence of accompanying symptoms. There is no specific management or treatment that is applicable to all forms of brachydactyly. Plastic surgery is only indicated if the brachydactyly affects hand function or for cosmetic reasons, but is typically not needed. Physical therapy and ergotherapy may ameliorate hand function. Prognosis for the brachydactylies is strongly dependent on the nature of the brachydactyly, and may vary from excellent to severely influencing hand function. If brachydactyly forms part of a syndromic entity, prognosis often depends on the nature of the associated anomalies.
Topics: Child, Preschool; Fingers; Foot; Foot Deformities, Congenital; Hand; Hand Deformities, Congenital; Humans; Infant; Pedigree; Radiography; Toes
PubMed: 18554391
DOI: 10.1186/1750-1172-3-15