The expanding panorama of split hand foot malformation (original) (raw)
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Autosomal recessive split-hand/split-foot malformation
Split-hand/split-foot malformation (SHFM), a congenital limb malformation, occurs due to the absence of the central rays of autopod that results in a deep median cleft of the hand and/or foot. It is also known as ectrodactyly or lobster claw hand. Although SHFM is mostly autosomal dominant, there are isolated case reports which indicate that it can be autosomal recessive. We are reporting a case of ectrodactyly with autosomal recessive mode of inheritance. KEYWORDS: Autosomal recessive, ectrodactyly, split-hand/split-foot malformation
Split hand/split-foot malformations: a report of four cases in a family with variable presentations
International Journal of Research in Medical Sciences, 2015
Split hand/split-foot malformation is a congenital anomaly with failure of development of the central digital rays of hand or foot to a variable extent. It is characterized by hypoplasia/aplasia of the phalanges, toes, metacarpals and metatarsals. The presentation may be an isolated anomaly or may be associated with syndrome and thus have variable pattern of inheritance. We report a family of 10 members; four of which are affected with autosomal recessive pattern of inheritance. We discuss here the clinical presentation, genetic inheritance, prenatal diagnosis and treatment for the malformation.
Mouse model of split hand/foot malformation type I
Genesis, 2002
Split hand/foot malformation type I (SHFM1) disease locus maps to chromosome 7q21.3-q22, a region that includes the distal-less-related (dll) genes DLX5 and DLX6. However, incomplete penetrance, variable expressivity, segregation distortion, and syndromic association with other anomalies have so far prevented the identification of the SHFM1 gene(s) in man. Here we show that the targeted double inactivation of Dlx5 and Dlx6 in the mouse causes in homozygous mutant animals bilateral ectrodactyly with a severe defect of the central ray of the hindlimbs, a malformation typical of SHFM1. This is the first evidence that the role of dll/Dlx genes in appendage development is conserved from insects to mammals and proves their involvement in SHFM1. genesis 33:97–101, 2002. © 2002 Wiley-Liss, Inc.
Split Hand/Foot Malformation about Two Family Cases
Open Journal of Pediatrics, 2023
Split hand/foot malformation (SHFM), formerly known as ectrodactyly is a rare congénital anomaly, its incidence varies from 1/8.500 to 1/25.000 live birth. It mainly affects the development of the limbs, its clinical variability is standard, can present as an isolated feature or as a syndrome associated with other congenital anomalies. Our objective was to present the two cases of SHFM, and to review the literature on the clinical aspects and discuss a probable origin. The father went to school and is a driver because the malformations concerned only the fingers, were less severe, and did not prevent the realization of certain simple gestures of the daily life. On the other hand, the malformations of the fingers of the newborn were severe and the absence of the thumbs compromised the later prehension function. Also the association of a microglossia and a cleft palate contributed to a weight loss that justified hospitalization. The clinical presentation of split hands and feet is variable and the prognosis depends on the type of anomaly. Familial cases suggest a probable genetic origin. Genetic testing is necessary to establish genetic counseling.
Copy-number variants and candidate gene mutations in isolated split hand/foot malformation
Journal of human genetics, 2017
Split hand/foot malformation (SHFM) is a congenital limb deficiency with missing or shortened central digits. Some SHFM genes have been identified but the cause of many SHFM cases is unknown. We used single-nucleotide polymorphism (SNP) microarray analysis to detect copy-number variants (CNVs) in 25 SHFM cases without other birth defects from New York State (NYS), prioritized CNVs absent from population CNV databases, and validated these CNVs using quantitative real-time polymerase chain reaction (qPCR). We tested for the validated CNVs in seven cases from Iowa using qPCR, and also sequenced 36 SHFM candidate genes in all the subjects. Seven NYS cases had a potentially deleterious variant: two had a p.R225H or p.R225L mutation in TP63, one had a 17q25 microdeletion, one had a 10q24 microduplication and three had a 17p13.3 microduplication. In addition, one Iowa case had a de novo 10q24 microduplication. The 17q25 microdeletion has not been reported previously in SHFM and included tw...
The Genetics of Split-Hand/Foot Malformation (SHFM) -A Pakistani Perspective
Split-hand/foot malformation (SHFM) is a multifaceted, congenital malformation of rare limb developments including deep median clefts of hands and feet, and aplasia and/or hypoplasia of the phalanges. Highly diverse in its presentation, SHFM can range from mild abnormalities of a single limb to severe defect of all four limbs and can occur as isolated (non-syndromic) or part of a complex syndrome. To date six forms of isolated SHFM harboring autosomal dominant, autosomal recessive and X-linked inheritance has been reported globally. In Pakistan, only autosomal recessive and X-linked families have been reported. The review aims to systematically read and analyze various types of isolated SHFM prevalent in Pakistani population.
Split-hand/foot malformation - molecular cause and implications in genetic counseling
Journal of Applied Genetics, 2014
Split-hand/foot malformation (SHFM) is a congenital limb defect affecting predominantly the central rays of the autopod and occurs either as an isolated trait or part of a multiple congenital anomaly syndrome. SHFM is usually sporadic, familial forms are uncommon. The condition is clinically and genetically heterogeneous and shows mostly autosomal dominant inheritance with variable expressivity and reduced penetrance. To date, seven chromosomal loci associated with isolated SHFM have been described, i.e., SHFM1 to 6 and SHFM/SHFLD. The autosomal dominant mode of inheritance is typical for SHFM1, SHFM3, SHFM4, SHFM5. Autosomal recessive and X-linked inheritance is very uncommon and have been noted only in a few families. Most of the known SHFM loci are associated with chromosomal rearrangements that involve small deletions or duplications of the human genome. In addition, three genes, i.e., TP63, WNT10B, and DLX5 are known to carry point mutations in patients affected by SHFM. In this review, we focus on the known molecular basis of isolated SHFM. We provide clinical and molecular information about each type of abnormality as well as discuss the underlying pathways and mechanism that contribute to their development. Recent progress in the understanding of SHFM pathogenesis currently allows for the identification of causative genetic changes in about 50 % of the patients affected by this condition. Therefore, we propose a diagnostic flow-chart helpful in the planning of molecular genetic tests aimed at identifying disease causing mutation. Finally, we address the issue of genetic counseling, which can be extremely difficult and challenging especially in sporadic SHFM cases.
Evidence for an additional locus for split hand/foot malformation in chromosome region 8q21.11–q22.3
American Journal of Medical Genetics Part A, 2006
We identified a family where five members had nonsyndromic ectrodactyly. There were three known instances of nonpenetrance. Although four individuals had unilateral cleft hand, one individual had more severe, bilateral and asymmetric absence of the digits. None had foot abnormalities. After exclusion of linkage of SHFM in this family to five known loci, a genome wide scan was performed with DNA from 5 affected and 15 unaffected members of this family. Suggestive evidence for linkage of ectrodactyly to 8q was obtained on the basis of a maximum LOD score of 2.54 at theta (max) ¼ 0 with GAAT1A4. Critical recombinants place the ectrodactyly gene in this family in a 16 cM (21 Mb) interval between D8S1143 and D8S556. Mutational analysis of two candidate genes (FZD6, GDF6) did not identify any mutations in affected members of this family. Our data indicate further genetic heterogeneity for ectrodactyly and suggest the presence of an additional SHFM locus in chromosome region 8q21.11-q22.3. ß
Split-hand/split-foot malformation (SHFM) is a severe form of congenital limb deformitycharacterized by the absence of one or more digits and/or variable degree of median clefts ofhands and feet. The present study describes an investigation of a consanguineous family of Pakistani origin segregating SHFM in an autosomal recessive manner. Human genome scan using SNP markers followed by whole exome sequencing revealed a frameshift deletion (c.409delA, p.Ser137Alafs*19) in the EPS15L1 gene located on chromosome 19p13.11. This is the first biallelic variant identified in the EPS15L1 gene underlying SHFM. Our findings reportthe first direct involvement of EPS15L1 gene in the development of human limbs.