Cushing proximal symphalangism and the NOG and GDF5 genes

Plett, Sara; Berdon, Walter E.; Cowles, Robert A.; Öklü, Rahmi; Campbell, John B.

doi:10.1007/s00247-007-0675-y

Cited by 13 publications

(15 citation statements)

References 5 publications

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“…At the most severe end of this spectrum is the multiple synostoses syndrome (SYNS1), which causes severe and widespread joint involvement including the hips, vertebrae and the elbows[1,8]. …”

Section: Discussionmentioning

confidence: 99%

“…NOG maps to chromosome 17 and encodes the protein Noggin (NOG), a bone morphogenic protein (BMP) inhibitor expressed at the sites of joint development[1]. In the formation of the human skeleton BMPs induce mesenchymal cell proliferation and differentiation into chondroblasts, recruit chondrocytes and promote cartilage formation[1,9]. NOG inhibits cartilage development, leading to separation of the cartilage and thus joint formation[1,9].…”

Section: Discussionmentioning

confidence: 99%

“…In the formation of the human skeleton BMPs induce mesenchymal cell proliferation and differentiation into chondroblasts, recruit chondrocytes and promote cartilage formation[1,9]. NOG inhibits cartilage development, leading to separation of the cartilage and thus joint formation[1,9]. NOG mutations lead to under expression of NOG resulting in high levels of BMPs, cartilage overgrowth and the absence of joint formation, which affects individuals with SYM1[1,8-11].…”

Section: Discussionmentioning

confidence: 99%

“…Proximal symphalangism (SYM1) is an autosomal dominant developmental disorder affecting joint formation[1]. It is characterized by variable fusions of the proximal interphalangeal joints of the hands, typically of the ring and little finger, with the thumb typically being spared.…”

Section: Introductionmentioning

confidence: 99%

“…It is characterized by variable fusions of the proximal interphalangeal joints of the hands, typically of the ring and little finger, with the thumb typically being spared. SYM1 is frequently associated with coalition both of the tarsal bones and the ear ossicles, resulting in conductive hearing loss[1]. This rare association was first reported by Cushing in 1916 and subsequently by Drinkwater in 1917 for the Brown and Talbot families respectively[2,3].…”

Section: Introductionmentioning

confidence: 99%

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Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family

Leonidou

Irving

Holden

et al. 2016

WJO

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Proximal symphalangism (SYM1B) (OMIM 615298) is an autosomal dominant developmental disorder affecting joint fusion. It is characterized by variable fusions of the proximal interphalangeal joints of the hands, typically of the ring and little finger, with the thumb typically being spared. SYM1 is frequently associated with coalition of tarsal bones and conductive hearing loss. Molecular studies have identified two possible genetic aetiologies for this syndrome, NOG and GDF5. We herein present a British caucasian family with SYM1B caused by a mutation of the GDF5 gene. A mother and her three children presented to the orthopaedic outpatient department predominantly for feet related problems. All patients had multiple tarsal coalitions and hand involvement in the form of either brachydactyly or symphalangism of the proximal and middle phalanx of the little fingers. Genetic testing in the eldest child and his mother identified a heterozygous missense mutation in GDF5 c.1313G>T (p.R438L), thereby establishing SYM1B as the cause of the orthopaedic problems in this family. There were no mutations identified in the NOG gene. This report highlights the importance of thorough history taking, including a three generation family history, and detailed clinical examination of children with fixed planovalgus feet and other family members to detect rare skeletal dysplasia conditions causing pain and deformity, and provides details of the spectrum of problems associated with SYM1B.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family

Leonidou

Irving

Holden

et al. 2016

WJO

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Foot anomalies and proximal symphalangism

et al. 2012

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A 2-week-old girl born at term (by vaginal delivery and without antenatal or perinatal events) was referred as having ''bilateral talipes and bilateral proximal symphalangism of little and ring fingers.'' The ''talipes'' was atypical with marked equinus and varus, but no cavus or adductus of the midfoot. Her mother had both symphalangism (absence of proximal interphalangeal joints) of middle, ring, and little fingers bilaterally and fixed pes planus with a rigid fixed hindfoot-and these deformities had also been present from birth. The maternal grandmother was similarly affected. However, the neonatal subject has an unaffected older sibling; maternal siblings are also unaffected. The three affected people did not have other obvious musculoskeletal abnormalities (elbow examination of the girl and her mother were normal and there were no peripheral stigmata of spinal anomalies). There was no history of musculoskeletal anomalies on the father's side. IMAGESRadiographs of the mother's left hand and foot are given in Figures 1 and 2, respectively. The radiographs of the mother's left foot (Fig. 2) show fusions of the middle and distal phalanges of the 3rd, 4th, and 5th toes. The distal aspect of the navicular is dome-shaped ( Fig. 2A).There are fusions of (i) the second metatarsal base to the intermediate cuneiform, (ii) the lateral cuneiform to the cuboid, and (iii) the talus with the navicular-these are best seen on the oblique view (Fig.2B). The lateral view (Fig. 2C) shows a planus (¼flat) deformity with no calcaneal pitch and absence of the lateral longitudinal arch.The pes planus causes the rays of the foot to be superimposed on the lateral view (Fig. 2C) which can cause confusion in the interpretation, e.g., a shadow at the base of the third metatarsal lies across the medial cuneiform, which makes its definition awkward.Tarsal and other foot coalitions thus co-exist with symphalangism in the mother.2. The deformity of the feet in the child was atypical for talipes given the lack of midfoot cavus and adductus. This reflects the likely underlying cause-as being due to a syndrome involving symphalangism and multiple foot coalitions. The feet of our patient were therefore treated with a modified Kite's method (as opposed to the Ponseti regime (Ponseti, 1996) which is dependent on the absence of coalitions) with serial casting and pressure under the calcaneo-

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Interstitial duplication of 20q11.22q13.11: A case report and review of literature

Goetzinger

Starks

Dillahunt

et al. 2021

Molec Gen & Gen Med

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Background Reports of interstitial duplication of chromosome 20q11 are rare with only nine published patients to date. Methods We performed karyotype and chromosomal microarray analysis on a peripheral blood sample for our patient and reviewed the genes in the region to provide genotype–phenotype correlation. Results Clinical features of the patient include minor dysmorphic facial features, shorthands and feet, bilateral conductive hearing loss, global developmental delay, and behavioral issues with attention deficit hyperactivity disorder. Together with previously published cases of 20q11 duplication, we show that patients with overlapping duplications share a similar clinical phenotype of dysmorphic craniofacial features and developmental delay. Conclusion We report an 8‐year‐old girl with a 9.1 Mb interstitial duplication of chromosome 20q11.22q13.11. Our observations suggest that a novel duplication syndrome and documentation of similar cases will further help clarify the phenotype.

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Cushing proximal symphalangism and the NOG and GDF5 genes

Cited by 13 publications

References 5 publications

Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family

Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family

Foot anomalies and proximal symphalangism

Interstitial duplication of 20q11.22q13.11: A case report and review of literature

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