Polyalanine repeat expansion mutation of the HOXD13 gene in a Chinese family with unusual clinical manifestations of synpolydactyly

Synpolydactyly (SPD) is an autosomal dominant limb malformation caused by mutations in the gene HOXD13. We investigated a Chinese family in which three individuals across three generations were affected with distinctive limb malformations. We extracted genomic DNA from the affected and three unaffected individuals from this family as well as 100 unrelated controls, for mutation detection by DNA sequencing. The family was characterized by camptodactyly and symphalangism of fingers two to five, transverse phalanx and osseous fusion of the third metacarpal with the proximal phalanx, as well as the coexistence of mild and more severe bilateral phenotypes. We identified a duplication mutation, c. 186-212dup, in exon 1 of the HOXD13 gene in the affected individuals from this family; it was not present in the unaffected individuals or the 100 unrelated individuals. And we also did not find polymorphism among the controls. This study has expanded the phenotypic spectrum of known HOXD13 polyalanine repeat mutations and provided more information about the polymorphic nature of the polyalanine repeat. In addition, new clinical manifestations have been added to the spectrum of possible synpolydactyly phenotypes.     

De novo complete trisomy 5p: clinical and neuroradiological findings

A Thai mother and son with distal symphalangism and other associated abnormalities are reported. Distal and middle phalanges of fingers and toes 2-5 were either aplastic/hypoplastic or fused between the corresponding digits. The second fingers and fourth fingernails were most severely affected in both patients. The mother's hands were less severely affected; the middle and distal phalanges of her hands were malformed and fused. Besides the absence of fusion lines, the shape of the fused middle and distal phalanges was quite different from that of other types of fusion, i.e., fused bones in both patients did not maintain the normal configuration of bone, referring to as "middle-distal phalangeal complex". Distal symphalangism was observed in toes 2-5 of the mother and in toe 3 of the son. Both patients had additional clinical manifestations such as narrowing of the zygomatic arch, dental pulp stone, microdontia of a mandibular permanent central incisor, cone-shaped epiphyses of middle phalanges of fingers, and absence of scaphoid, trapezium, trapezoid, and pisiform bones. Mutation analysis of NOG and ROR2, the genes responsible for proximal symphalangism and brachydactyly type B, respectively, was negative.     

De novo complete trisomy 5p: Clinical and neuroradiological findings

A Thai mother and son with distal symphalangism and other associated abnormalities are reported. Distal and middle phalanges of fingers and toes 2–5 were either aplastic/hypoplastic or fused between the corresponding digits. The second fingers and fourth fingernails were most severely affected in both patients. The mother's hands were less severely affected; the middle and distal phalanges of her hands were malformed and fused. Besides the absence of fusion lines, the shape of the fused middle and distal phalanges was quite different from that of other types of fusion, i.e., fused bones in both patients did not maintain the normal configuration of bone, referring to as “middle‐distal phalangeal complex”. Distal symphalangism was observed in toes 2–5 of the mother and in toe 3 of the son. Both patients had additional clinical manifestations such as narrowing of the zygomatic arch, dental pulp stone, microdontia of a mandibular permanent central incisor, cone‐shaped epiphyses of middle phalanges of fingers, and absence of scaphoid, trapezium, trapezoid, and pisiform bones. Mutation analysis of NOG and ROR2, the genes responsible for proximal symphalangism and brachydactyly type B, respectively, was negative. © 2002 Wiley‐Liss, Inc.     

Proximal symphalangism with "coarse" facial appearance, mixed hearing loss, and chronic renal failure: new malformation syndrome?

A 25-year-old man is described with short stature, moderate mental retardation, an abnormal facial appearance, a webbed neck, skeletal abnormalities including proximal symphalangism of bilateral second through fifth fingers, mixed hearing loss, and slowly progressive, sclerosing nephropathy. He was large at birth with generalized edema, more pronounced around the jaw, neck and the upper part of the body, but became short with increasing age, and currently measures 143 cm (-4.9 SD). He had intermittent proteinuria and slowly progressive deterioration of the renal function. A biopsy of the left kidney showed global glomerular sclerosis with interstitial fibrosis. He was placed on maintenance peritoneal dialysis at age 17 years, and now on hemodialysis. His skeletal abnormalities included, in addition to proximal symphalangism, stenosis of the cervical canal, scoliosis, brachydactyly of the hands, hypoplastic hip joints, and pes valgus. Other abnormalities noted were a communicating defects of the diaphragm (surgically corrected), bilateral inguinal hernia and cryptorchidism. These clinical manifestations indicate a hitherto undescribed combination of manifestations and nephropathy.     

Proximal symphalangism with “coarse” facial appearance,mixed hearing loss,and chronic renal failure: New malformation syndrome?

A 25‐year‐old man is described with short stature, moderate mental retardation, an abnormal facial appearance, a webbed neck, skeletal abnormalities including proximal symphalangism of bilateral second through fifth fingers, mixed hearing loss, and slowly progressive, sclerosing nephropathy. He was large at birth with generalized edema, more pronounced around the jaw, neck and the upper part of the body, but became short with increasing age, and currently measures 143 cm (−4.9 SD). He had intermittent proteinuria and slowly progressive deterioration of the renal function. A biopsy of the left kidney showed global glomerular sclerosis with interstitial fibrosis. He was placed on maintenance peritoneal dialysis at age 17 years, and now on hemodialysis. His skeletal abnormalities included, in addition to proximal symphalangism, stenosis of the cervical canal, scoliosis, brachydactyly of the hands, hypoplastic hip joints, and pes valgus. Other abnormalities noted were a communicating defects of the diaphragm (surgically corrected), bilateral inguinal hernia and cryptorchidism. These clinical manifestations indicate a hitherto undescribed combination of manifestations and nephropathy. © 2001 Wiley‐Liss, Inc.     

Distal arthrogryposis type 1: Clinical analysis of a large kindred

We describe the clinical findings of 15 individuals in a large kindred affected with distal arthrogryposis type 1A (DA1A). The most consistent findings among individuals were overlapping fingers at birth, abnormal digital flexion creases, and foot deformities, including talipes equinovarus and vertical talus. There was marked intrafamilial variation in the expression of DA1A. Linkage mapping of the locus for DA1A suggests that the use of strict diagnostic criteria excludes unaffected individuals rigorously, but can produce incomplete ascertainment of affected individuals. In the context of an affected family, the range of phenotypes consistent with a diagnosis of DA1A needs to be expanded. © 1996 Wiley-Liss, Inc.     

Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome

Proximal symphalangism is an autosomal-dominant disorder with ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive deafness. These symptoms are shared by another disorder of joint morphogenesis, multiple synostoses syndrome. Recently, it was reported that both disorders were caused by heterozygous mutations of the human noggin gene (NOG). To date, seven mutations of NOG have been identified from unrelated families affected with joint morphogenesis. To characterize the molecular lesions of proximal symphalangism, we performed analyses of NOG in three Japanese individuals with proximal symphalangism. We found three novel mutations: g.551G>A (C184Y) in a sporadic case of symphalangism, g.386T>A (L129X) in a familial case of symphalangism, and a g.58delC (frameshift) in a family with multiple synostosis syndrome. Characteristic genotype-phenotype correlations have not been recognized from the mutations in the NOG gene.     

Herrmann multiple synostosis syndrome with neurological complications caused by spinal canal stenosis

A young man was found to have multiple synostosis syndrome type I after presenting with a neck injury causing a cervical spinal cord contusion. Neurological symptoms and signs suggested spinal cord compression. Magnetic resonance (MR) and computerized tomography (CT) imaging of the spine showed spinal canal stenosis with cord compression at C3-C6, a deformed spinal canal flattened in the anteroposterior dimension, vertebral fusions and deformed lateral processes of the vertebrae. He had a long broad nose with hypoplasia of the alae nasi, conductive hearing loss requiring hearing aids, muscular build, stiff spine, prominent acromia, pectus excavatum, ischial prominences, short fifth fingers, fusion at the proximal interphalangeal joints of the fifth fingers with indistinct overlying creases, and toe syndactyly. Spinal cord stenosis is a serious complication of multiple synostosis syndrome, that should be kept in mind in considering the risk of neck or back injury associated with certain sports or other activities. In both the multiple synostosis syndrome and the less severe proximal symphalangism deafness syndrome, mutations have been detected in the human homologue of the noggin gene on chromosome 17q21-q22.     

Kindling phenomena induced by the repeated short-term high potassium stimuli in the ventral hippocampus of rats: on-line monitoring of extracellular glutamate overflow

Recent research indicates that areas of the primary somatosensory (SI) and primary motor cortex show massive cortical reorganization after amputation of the upper arm, forearm or fingers. Most of these studies were carried out months or several years after amputation. In the present study, we describe cortical reorganization of areas in the SI of a patient who underwent amputation of the traumatized middle and ring fingers of his right hand 10 days before cortical magnetic source imaging data were obtained. Somatosensory-evoked magnetic fields (SEF) to mechanical stimuli to the finger tips were recorded and single moving dipoles were calculated using a realistic volume conductor model. Results reveal that the dipoles representing the second and fifth fingers of the affected hand were closer together than the comparable dipoles of the unaffected hand. Our findings demonstrate that neural cell assemblies in SI which formerly represented the right middle and ring fingers of this amputee became reorganized and invaded by neighbouring cell assemblies of the index and little finger of the same hand. These results indicate that functional plasticity occurs within a period of 10 days after amputation.     

A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families

Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal bones. We identified and characterized two five-generation Chinese families with SYM1. The two families share some similarities (e.g., osseous fusion of interphalangeal joints of the 2-4 fingers) with SYM1 families with mutations in the NOG gene or the family with mutation R438L recently reported in the GDF5 gene (encoding a bone morphogenetic protein family member). However, they show some unique features including the absence of cuboid bone, the lack of shortness of the first and fifth metacarpal bones, and manifestation of flat feet. Genome-wide linkage analysis of the two families mapped the disease gene to marker D20S112 with a combined LOD score of 4.32. Mutational analysis revealed a novel E491K mutation in the GDF5 gene in both families. The mutation occurs at a highly conserved residue in the TGF-beta domain of GDF5 and represents the second GDF5 mutation identified for SYM1 to date. The E491K mutation co-segregated with the affected individuals in the two families, and did not exist in unaffected family members or 200 normal controls. These results indicate that defects in GDF5 can cause SYM1 in the Chinese population, and expand the spectrum of clinical phenotypes associated with mutant GDF5.     

Differential impairment of individuated finger movements in humans after damage to the motor cortex or the corticospinal tract

The purpose of this study was to quantify the long-term loss of independent finger movements in humans with lesions relatively restricted to motor cortex or corticospinal tract. We questioned whether damage to the motor cortex or corticospinal tract would permanently affect the ability to move each finger to the same degree or would affect some fingers more than others. People with pure motor hemiparesis due to ischemic cerebrovascular accident were used as our experimental sample. Pure motor hemiparetic and control subjects were tested for their ability to make cyclic flexion/extension movements of each finger independently. We recorded their finger joint motion using an instrumented glove. The fingers of control subjects and of the unaffected hands (ipsilateral to the lesion) of hemiparetic subjects moved relatively independently. The fingers of the affected hands (contralateral to the lesion) of hemiparetic subjects were differentially impaired in their ability to make independent finger movements. The independence of the thumb was normal; the independence of the index finger was slightly impaired, while the independence of the middle, ring, and little fingers was substantially impaired. The differential long-term effects of motor cortical or corticospinal damage on finger independence may result from rehabilitative training emphasizing tasks requiring independent thumb and index movements, and from a greater ability of the spared components of the neuromuscular system to control the thumb independently compared with the other four fingers.     

指深屈肌腱及指伸肌腱止点的解剖研究

目的　通过解剖研究指深屈肌腱及指伸肌腱在远节指骨基底掌侧和背侧止点平面的差别，为西摩骨折发生机制提供解剖学依据。 方法　手部残肢10具，其中左手3例，右手7例，均为男性患者，年龄24~58岁。2~5指分别有10指，全部手指无外伤手术史、无畸形。自远节指间关节水平掌侧及背侧分别切开，于末节指骨水平分离各指的指深屈肌腱及指伸肌腱，记录其与末节指骨掌侧及背侧关节面的距离，比较指深屈肌腱及指伸肌腱在末节指骨掌、背侧的止点水平。 结果　指深屈肌腱止点近端至关节面距离：示指（2.19±0.27）mm，中指（2.50±0.14）mm，环指（2.23±0.16）mm，小指（1.83±0.19）mm；指伸肌腱止点近端至关节面距离：示指（0.12±0.02）mm，中指（0.18±0.02）mm，环指（0.12±0.05）mm，小指（0.06±0.01）mm；各指差异有统计学意义（P＜0.05）。指深屈肌腱止点中点至关节面距离：示指（3.73±0.45）mm，中指（4.33±0.45）mm，环指（3.53±0.46）mm，小指（3.16±0.41）mm；指伸肌腱止点中点至关节面距离：示指（1.77±0.06）mm，中指（1.76±0.20）mm，环指（1.77±0.06）mm，小指（1.47±0.10）mm；各指差异有统计学意义（P＜0.05）。 结论　指伸肌腱在末节指骨基底的止点较指深屈肌腱的止点距关节面更近，为西摩骨折的发生机制提供了解剖依据。     

指深屈肌腱及指伸肌腱止点的解剖研究

目的　通过解剖研究指深屈肌腱及指伸肌腱在远节指骨基底掌侧和背侧止点平面的差别,为西摩骨折发生机制提供解剖学依据。 方法　手部残肢10具,其中左手3例,右手7例,均为男性患者,年龄24~58岁。2~5指分别有10指,全部手指无外伤手术史、无畸形。自远节指间关节水平掌侧及背侧分别切开,于末节指骨水平分离各指的指深屈肌腱及指伸肌腱,记录其与末节指骨掌侧及背侧关节面的距离,比较指深屈肌腱及指伸肌腱在末节指骨掌、背侧的止点水平。 结果　指深屈肌腱止点近端至关节面距离：示指（2.19±0.27）mm,中指（2.50±0.14）mm,环指（2.23±0.16）mm,小指（1.83±0.19）mm;指伸肌腱止点近端至关节面距离：示指（0.12±0.02）mm,中指（0.18±0.02）mm,环指（0.12±0.05）mm,小指（0.06±0.01）mm;各指差异有统计学意义（P＜0.05）。指深屈肌腱止点中点至关节面距离：示指（3.73±0.45）mm,中指（4.33±0.45）mm,环指（3.53±0.46）mm,小指（3.16±0.41）mm;指伸肌腱止点中点至关节面距离：示指（1.77±0.06）mm,中指（1.76±0.20）mm,环指（1.77±0.06）mm,小指（1.47±0.10）mm;各指差异有统计学意义（P＜0.05）。 结论　指伸肌腱在末节指骨基底的止点较指深屈肌腱的止点距关节面更近,为西摩骨折的发生机制提供了解剖依据。     

Selective entrapment palsy of the posterior interosseous nerve: A case report

A 27-year-old woman developed a paralysis of her right hand, which affected the power of extension of her middle, ring, and little fingers, but spared the index finger and the thumb. There was a past history of injury of the elbow and dislocation of the head of the radius, and compression of the posterior interosseous nerve was suspected. After confirmation of the diagnosis by nerve conduction tests, the course of the nerve was explored surgically in the antecubital fossa. Compression seemed to be a result of two small vessels put under tension by subluxation of the head of the radius. Division of the vessels led to rapid recovery of function. The affected and unaffected muscles in this paralysis are supplied by separate branches of the posterior interosseous nerve. It seems likely that the fibers of the affected branch had been selectively compressed within the trunk of the posterior interosseous nerve. This suggests that there is sharp topographical localization of branches within the trunk of the nerve.     

Congenital stapes ankylosis, broad thumbs, and hyperopia: report of a family and refinement of a syndrome

We report on a family with conductive hearing loss due to congenital stapes ankylosis, and with hyperopia, broad thumbs, and broad first toes. Neither of the studied relatives had symphalangism, possibly distinguishing this syndrome as an entity separate from the facio-audio-symphalangism and proximal symphalangism syndromes. An alternative possibility is that this family falls within the spectrum of the facioaudio-symphalangism and proximal symphalangism syndromes. Visualization of the ossicular chain, and ophthalmologic and radiologic studies are important in the evaluation of families with congenital conductive hearing loss. A characteristic physiognomy in our patients is present; this autosomal dominant syndrome was first described by Teunissen and Cremers [1990: Laryngoscope 100:380-384].     

Alport syndrome with diffuse leiomyomatosis

A Thai girl with a unique combination of limb and craniofacial anomalies is reported. Manifestations include blepharoptosis; prominent nose; hypodontia; multiple, hyperplastic frenula; and dysplastic ears. Limb anomalies include short stature, postaxial polydactyly of both hands and the left foot, proximal and distal symphalangism of fingers, and congenital absence of the distal phalanges of toes 2-5. Mutation analyses of NOG and GDF5, the genes responsible for symphalangism-related syndromes, were negative.     

Distal symphalangism associated with camptodactyly.

A Japanese family in which four patients in three generations had distal symphalangism associated with camptodactyly is reported. All of these patients had extension limitation of the proximal interphalangeal joints of the toes of both feet. Radiographs of the hands and feet, undertaken in three cases, showed no bone fusion of the distal and proximal interphalangeal joints. This malformation is caused by an autosomal dominant gene. To our knowledge, no previous case of distal symphalangism with extension limitation of the proximal interphalangeal joints has been reported.     

Leiomyoma of uterus in a patient with ring chromosome 12: Case presentation and literature review

We report on a 30-year-old woman with de novo ring chromosome 12 mosaicism, 46,XX,r(12)(p13.3q24.3)/46,XX. In addition to the clinical manifestations generally observed in “ring syndrome” cases such as growth retardation, short stature, microcephaly, and mental deficiency, she had a broad nasal bridge, micrognathia with overbite, under-developed breasts, mild dorsal scoliosis, clinodactyly of the fifth fingers with a single interdigital crease, symphalangism of thumbs, tapering fingers, mild cutaneous syndactyly between the second and third toes, multiple café-au-lait spots, sebaceous acne on the face and back, and mild dystrophic toenails. She developed a large, pedunculated uterine leiomyoma at age 28 years. To our knowledge, uterine leiomyoma in association with r(12) has not been reported previously. However, a gain of chromosome 12 and translocations involving 12q14-15 have been described. © 1996 Wiley-Liss, Inc.     

Differential control of the digits of the human hand: evidence from digital anaesthesia and weight matching

The present study assessed changes in perceived heaviness of weights lifted by the thumb, index, ring and little fingers during anaesthesia of the “lifting” digit. Subjects (n = 19) lifted weights solely by flexion of the distal joint of the digit, using a bilateral weight-matching paradigm. Changes in perceived heaviness during anaesthesia differed in both their sign and magnitude for the different digits. Anaesthesia of the thumb and index finger produced large increases in perceived heaviness (median, thumb: +41%; index finger: +13%), whereas anaesthesia of the ring finger decreases perceived heaviness (–14%). Anaesthesia of the little finger also reduced perceived heaviness (median, –21%; n = 6). Because perceived heaviness is biased by signals of motor commands, these findings suggest a nett facilitatory reflex effect of the digital nerve inputs from the thumb and index fingers onto their respective flexor motoneurones with the corresponding effect for the ring and little fingers being inhibitory. Received: 19 May 1997 / Accepted: 30 June 1997     

An anomalous muscle in children with congenital talipes

An anomalous calf flexor muscle has been observed in five children (involving 7 feet) in 125 surgical corrections of congenital talipes equinovarus deformity (5.6%). The sex, frequency of bilateral to unilateral deformity, position of the child in the family, maternal age, birth weight, gestation period, and type of delivery did not distinguish these children from those without the anomalous muscle, but they did have a greater frequency of first-degree relatives with talipes. © 1996 Wiley-Liss, Inc.