Triphalangeal thumb and brachy-ectrodactyly syndrome

Two patients with triphalangeal thumbs-ectrodactyly syndrome are described. The first case is a 4-year-old female with triphalangeal thumbs, preaxial polydactyly with rudimentary polydactyly of the 3rd finger of the right hand and ectro-syndactyly of feet. Her stillborn sister had triphalangeal thumbs and ectrodactyly of feet. The mother has triphalangeal thumbs, brachy-syndactyly of the left foot and ectro-syndactyly of the right one. The maternal grandmother has syndactyly of 1st, 2nd, 3rd toes and hypoplasia of the 3rd toe on the right foot. The second case is sporadic and shows triphalangeal thumbs, preaxial polydactyly of the right hand and bilateral lobster-claw feet. Our observations confirm the variability of clinical expression and support the autosomal dominant inheritance of the syndrome.     

Expanding the clinical spectrum of SOX18-related Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome

Pathogenic variants in SOX18 are associated with hypotrichosis-lymphedema-telangiectasia-renal defects syndrome (HLTRS) and hypotrichosis-lymphedema-telangiectasia syndrome (HLTS). Eleven patients with SOX18 related HLTRS/HLTS have been previously described. Cardinal features include varying degrees of hypotrichosis, lymphedema and telangiectasias. We report a 15-year-old female patient with a likely de novo SOX18 pathogenic variant identified on duo exome sequencing. In addition to the classic features, the currently reported patient presented with novel clinical features including musculoskeletal abnormalities and strikingly poor wound healing. Chronic skin ulcers have been a major cause of morbidity for the patient and have led to significant functional limitation. Further, our experience with wound management has been detailed. We hope to improve understanding of the clinical spectrum of this ultra-rare disorder by reviewing the phenotypic features in all reported patients including our patient.     

Polydactyly: Clinical and molecular manifestations

Polydactyly is a malformation during the development of the human limb, which is characterized by the presence of more than the normal number of fingers or toes. It is considered to be one of the most common inherited hand disorders. It can be divided into two major groups: Non-syndromic polydactyly or syndromic polydactyly. According to the anatomical location of the duplicated digits, polydactyly can be generally subdivided into pre-, post-axial, and mesoaxial forms. Non-syndromic polydactyly is often inherited with an autosomal dominant trait and defects during the procedure of anterior-posterior patterning of limb development are incriminated for the final phenotype of the malformation. There are several forms of polydactyly, including hand and foot extra digit manifestations. The deformity affects upper limbs with a higher frequency than the lower, and the left foot is more often involved than the right. The treatment is always surgical. Since the clinical presentation is highly diverse, the treatment combines single or multiple surgical operations, depending on the type of polydactyly. The research attention that congenital limb deformities have recently attracted has resulted in broadening the list of isolated gene mutations associated with the disorders. Next generation sequencing technologies have contributed to the correlation of phenotype and genetic profile of the multiple polydactyly manifestations and have helped in early diagnosis and screening of most non-syndromic and syndromic disorders.     

GLI基因与肢体发育相关性的研究进展

在肢体发育中,Sonic hedgehog(SHH)蛋白作为极化区(the zone of polarizing actiVity,ZPA)的调节因子,发挥着十分重要的作用。然而SHH是如何沿着肢体的前后轴发挥调控作用的还不是很清楚。最近的报道表明SHH主要是通过阻止转录因子GLI3裂解成抑制形式发挥作用,而后者也能够关闭SHH靶基因的表达。GLI基因家族的成员编码含有锌指结构的转录因子,主要对SHH的靶基因发挥调节作用。现就GLI基因在肢体发育中的表达特点及其临床意义进行综述。     

A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes

Polydactyly is a human inherited disorder caused by to anomalies in the genes involved in autopod development. The disorder segregates in both autosomal recessive and autosomal dominant form. Up till now, eleven genes causing non-syndromic polydactyly, have been identified. This includes ZNF141, GLI3, ZRS in LMBR1, MIPOL1, PITX1, IQCE, GLI1, FMA92A1, KIAA0825, STKLD1, and DACH1. In the present study, we have investigated a large consanguineous family of Pakistani origin segregating polydactyly in autosomal recessive pattern. Clinical examination of affected individuals revealed a non-syndromic form of the disorder. Genetic study based on homozygosity mapping and Sanger sequencing using DNA of the normal and affected individuals found a novel homozygous missense sequence variant [NM_005269.3: c.1133C > T, p.(Ser378Leu)] in the GLI1 located on human chromosome 12q13.3. In silico analysis of the identified variant showed a significant change in the secondary structure of the mutant protein that affects its function. Findings of the present study expand the mutation spectrum of the GLI1. In addition, the study will help in prevention of the disorder through carrier testing and bringing awareness among families affected with polydactyly.     

Polydactyly and fetal hydantoin syndrome: an additional component of the syndrome?

We report a 3-year-old girl with fetal hydantoin syndrome (FHS) whose mother had received phenytoin 600 mg/day throughout gestation. She had growth retardation, mental deficiency, craniofacial dysmorphism and iris colomobata specific to FHS. However, the patient did not have the distal phalangeal hypoplasia which is associated with FHS; instead, she had Polydactyly of the right foot. This seems to be the first FHS case in the literature with Polydactyly.     

复拇指畸形矫治术后的继发性畸形

目的探讨先天性复拇指畸形手术后的继发性畸形和处理方法。方法．对12例先天性复拇指畸形经矫治术后出现拇指侧偏、内收、虎口狭窄、骨骺残留等继发性畸形的患者，进行拇指指间关节融合、掌骨截骨、骨骺切除、虎口成型、拇短展肌止点重建等手术；以纠正畸形、改善拇指的外形及功能。结果术后随访3至6个月，除1例较术前稍有改善外，11例拇指的外形明显改善，拇指对掌、对指功能基本恢复。结论先天性复拇指畸形单纯手术切除后又出现继发性畸形，和过早(2岁以前)手术有关。患儿手指细小，组织结构辨认不清，可导致畸形矫治不彻底而出现继发性畸形。作者认为复拇指畸形的手术时机在2—6岁为好，畸形复杂者在学龄前手术为佳。