Symphalangism

Pasha, Amirala S.; Weimer, Melissa

doi:10.1002/art.39752

Cited by 2 publications

(2 citation statements)

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“…Babies with the classic, infantile form of Farber's disease present with symptoms within the first months of life and rarely survive beyond age 2-3 years. In infants, Farber's disease may present as an acute inflammatory condition mimicking JIA (4,9). Hand radiographs of a boy described by Kostik et al (4) showed thinning of the diaphysis and osteopenia, and it is likely that skeletal involvement in that boy may have progressed to look like the osteolysis in our patients.…”

Section: Discussionmentioning

confidence: 63%

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Bonafé

Kariminejad²,

et al. 2016

Arthritis & Rheumatology

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Objective. To establish a diagnosis and provide counseling and treatment for 3 adult patients from one family presenting with peripheral osteolysis.Methods. Following clinical and radiographic assessment, exome sequencing, targeted gene resequencing, and determination of enzyme activity in cultured fibroblasts were performed.Results. The proband (age 40 years) had a history of episodic fever and pain in childhood that subsided around puberty. He and 2 of his older sisters (ages 58 and 60 years, respectively) showed adult-onset progressive shortening of fingers and toes with redundancy of the overlying skin. Radiographs showed severe osteolysis of the distal radius and ulna, carpal bones, metacarpal bones, and phalanges. Sequencing of the known genes for recessively inherited osteolysis, MMP2 and MMP14, failed to show pathogenic mutations. Exome sequencing revealed compound heterozygosity for mutations c.505T>C (p.Trp169Arg) and c.760A>G (p.Arg254Gly) in ASAH1, the gene coding for acid ceramidase. Sanger sequencing confirmed correct segregation in the family, and enzyme activity in fibroblast cultures from the patients was reduced to~8% of that in controls, confirming a diagnosis of Farber's disease.Conclusion. Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long-term skeletal manifestations of acid ceramidase deficiency (Farber's disease) in what appear to be the oldest affected individuals known so far.

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Section: Discussionmentioning

confidence: 63%

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Bonafé

Kariminejad²,

et al. 2016

Arthritis & Rheumatology

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“…Proximal symphalangism is a rare genetic disorder of congenital limb malformation, characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and, in some cases, conductive deafness and premature ovarian failure [1, 2]. The typical features of proximal symphalangism are reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger [3, 4]. As early as in 1916, Cushing has described an American family with ankylosis of the proximal interphalangeal joints, and he named this heterozygote autosomal dominant disease as symphalangism [5].…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling

Liu

Wang

et al. 2019

BMC Med Genet

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BackgroundProximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants in Noggin (NOG), another is proximal symphalangism-1B (SYM1B), which is resulted from Growth Differentiation Factor 5 (GDF5) mutations.Case presentationHere, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygous NOG mutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing.ConclusionIn this study, we identified a novel NOG mutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum of NOG mutations and contributed to genetic diagnosis and counseling of families with SYM1A.

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Symphalangism

Cited by 2 publications

References 1 publication

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Identification of a novel mutation of NOG in family with proximal symphalangism and early genetic counseling

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