Limb Malformations Research Articles

REPRODUCIBILITY OF THE BASIC X-RAY PARAMETERS OF LOWER EXTREMITY DEFORMATIONS IN CHILDREN WITH SKELETAL DYSPLASIA

Introduction: axial deformities in the lower extremities of children lead to an uneven distribution of the load in different compartments of the knee joint, which can contribute to the development of osteoarthritis. Regardless of the cause of their occurrence, the main goal of treatment is the restoration of the mechanical axis. Various calculation methods are used to determine the amount of deformity, its apex and the degree of required correction. The aim: to evaluate the reproducibility of the basic X-ray parameters characterizing the deformities of the lower extremities in the frontal plane in children with skeletal dysplasia based on the calculation of inter-rater reliability.Materials and methods: the article presents calculations of the main angulometric parameters of the knee joint (deviation of the mechanical axis — MAD, distal mechanical angle of the femur — mLDFA, proximal angle of the tibia — MPTA) in 18 patients with skeletal dysplasia (30 lower extremities) that had axial deformities of the lower extremities in the frontal plane at the level of the knee joint. The control group included the results of similar calculations of the angulometric parameters in 19 children (30 lower extremities) with valgus and varus deformities of the knee joint without skeletal dysplasia (idiopathic axial deformations, posttraumatic deformities, malformations of the lower limbs). The estimation of inter-expert reliability was made in the SPSSv. 23.Results: the analysis demonstrated that calculation of reference parameters in children without primary lesion of the growth plate has a high degree of inter-rater reliability: an intra-class correlation coefficient with a 95% confidence interval (ICC [95% CI]) when calculating the reference angles of mMPTA and mLDFA was 0.981% [0.971–0.991] and 0.993% [0.989–0.997] respectively, for MAD 0.996% [0.993–0.998]. When calculating the same parameters in children with skeletal dysplasia, the results differed. Thus, the intra-class correlation coefficient for the deviation of the mechanical axis was 0.861% [0.763–0.926] (which corresponds to the normal reproducibility of this parameter), for mMPTA — 0.586% [0.295–0.781], for mLDFA — 0.796% [0.653–0.892]. This indicates a low reproducibility and may lead to errors in the planning of correction of axial deformities of the lower limbs in children with skeletal dysplasia.Conclusion: when calculating the severity of axial deformities in the lower extremities in children with skeletal dysplasia, the most reproducible parameter is the determination of the deviation of the mechanical axis of the lower extremities as compared to the studied angulometric methods.

Phenotype analysis of Myo10 knockout mice lacking the motorized full‐length, but not the brain‐specific headless isoform

Unconventional myosin‐X (Myo10) is a MyTH4‐FERM and PH domain containing actin‐based motor protein which is widely expressed among vertebrate tissues. MyTH4‐FERM myosins are associated with protrusions enriched in bundled actin filaments. Full‐length (fl) Myo10 is best known for its localization to the tips of filopodia and for its ability to induce and regulate the formation of these dynamic finger‐like structures. At the cellular level, Myo10 has been implicated in diverse functions, including oriented cell migration, axon guidance, melanosome transfer, spindle assembly and phagocytosis. However, the physiological functions at the organismal level of this filopodial cargo carrier are not clear. We studied the phenotypes of Myo10 reporter knockout mice (Myo10tm2), to elucidate Myo10 function in vivo. Using Western blot analysis, we showed that in homozygous knockout Myo10tm2/tm2 mice, the expression of motorized fl Myo10 was deleted, but the brain‐specific headless (hdl) isoform was not abolished. Macroscopic examination of Myo10‐deficient mice revealed ventral coat pigmentation defects (100% penetrance) and a limb malformation, syndactyly, with a high penetrance of >95%. 24% of homozygous KO embryos developed exencephaly, a severe neural tube closure defect that is lethal. Magnetic resonance imaging (MRI) of isolated brains revealed, in contrast to mice lacking the Myo10 cargo protein DCC, intact cerebral commissures. Furthermore, Myo10 KO mice consistently displayed bilateral persistence of the hyaloid vasculature, visualized by MRI and retinal whole mount preparations, whereas retinal vascularization, phagocytosis and chemotactic behavior were not impaired. Confocal spinning disk microscopy confirmed that the hdl isoform of Myo10 does not induce filopodia and we found out that hdl Myo10 strongly localizes to the plasma membrane in dependency of its PH domains, supporting the auto‐inhibition model in which head‐tail interactions of fl Myo10 abolishes inactive monomer binding to PIP3‐rich membranes. In conclusion, Myo10 is important for normal vertebrate development, both prenatal (neural tube closure and digit separation) and postnatal (hyaloid regression).Support or Funding InformationDeutsche Forschungsgemeinschaft (DFG)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Mutations in the fourth β-propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers.

Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani-Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly. LRP4 inhibits LRP6/LRP5-mediated activation of canonical Wnt signaling and mediates sclerostin-dependent inhibition of bone formation. p.D1403H and p.Q1564K are located within the fourth β-propeller of the extracellular protein domain that has yet to be associated with human disease. Functional analyses of p.D1403H and p.Q1564K show that they significantly decrease LRP4's inhibition of Wnt signaling. These results suggest that variants in the fourth β-propeller of the extracellular protein domain may cause a phenotype distinct from previously characterized LRP4 variants.

Orthodontics and Moebius syndrome: an observational study.

Moebius syndrome is a rare condition characterized by bilateral facial and abducens nerve paralysis. The aim of this study is to evaluate the main orthodontic features and the frequency of associated clinical characteristics in patients with Moebius syndrome (MS). According to Terzis classifications, 58 patients with MS aged 8 months to 46 years old underwent orthodontics and clinical examination. Strabismus, upper and lower limb malformations, lip and palatal cleft were frequently associated with MS. Reduced TM movements were noted (48%). Cephalometric analysis did not allow identifying a typical facies and a characteristic cephalometric pattern; we have noticed a higher prevalence of Class II (56%) with micrognathia and excessive maxillary development probably due to the lack of lip seal. Early treatment is recommended, with a multidisciplinary approach to reduce the impact of sequelae on the lives of MS patients or their families. Early treatment is recommended, with a multidisciplinary approach to diminish the impact of sequelae on the lives of MS patients or their families.

Homozygous CHST11 mutation in chondrodysplasia, brachydactyly, overriding digits, clino-symphalangism and synpolydactyly

BackgroundCarbohydrate sulfotransferase 11 (CHST11) is a membrane protein of Golgi that catalyses the transfer of sulfate to position 4 of the N-acetylgalactosamine residues of chondroitin. Chondroitin sulfate is the predominant...

Clinical profile of congenital limb anomalies in neonates

Background: Reported birth prevalence of congenital limb defects vary from country to country. Epidemiological studies permit the timely detection of trends in congenital limb anomalies and the associations with other birth defects. The objective of this study was to know the prevalence and the variety of congenital limb anomalies and their association with other anomalies.Methods: A prospective observational study in which all newborns reported to the neonatal department were surveyed to find out the incidence, diversity and association of limb anomalies. Age of the mother, risk factors and other demographic data of the newborns was analyzed. Babies born less than 28 weeks were excluded from the study.Results: The prevalence was 6.34 per thousand live births. The majority of the neonates were term babies and female. 28 % of the babies were born out of consanguineous marriage. The mean age of the mother was 25. Median parity was 1. 9.52 % of the babies had a history of anomaly in the sibling. 4.76 % had a history of still birth. The most common congenital anomaly was congenital talipo equino varus. The other congenital limb anomalies observed were polydactyly, syndactyly, bifid thumb and absence of the radius. There were multiple congenital anomalies in 28.57 % of the babies.Conclusions: The study has given us an insight into the variety of congenital limb malformations and also into the possible etiological factors. A study done on a larger population would probably help us assess the incidence and pattern of occurrence of limb anomalies and help us counsel the parents.

Syndactyly genes and classification: a mini review

Syndactyly (Syn = together; Dactylos = digits) is the most common limb defect mostly characterized by webbing of digits. It may be webbing with or without bony fusion and inherited mostly in autosomal dominant manner, although also reported as autosomal recessive, X-linked or isolated entity. It also shows diverse clinical and phenotypic heterogeneity and mostly observed as unilateral or bilateral and symmetrical or asymmetrical forms. Syndactyly mostly occurs either as an isolated anomaly or as a part of a complex syndrome (+150 syndromes). Here, non-syndromic syndactyly has been classified according to genetic and molecular basis. The non-syndromic syndactyly has been classified into nine different types. Up till now, the major genes identified to cause hereditary syndactyly are mainly involved in the sonic hedgehog pathway and zone of polarizing activity. The present review mostly focuses on summarizing the recent advances in molecular genetics, including known genes and loci responsible for non-syndromic syndactyly. The present review will contribute to the understanding of the pathogenesis underlying non-syndromic and syndromic syndactyly, improving clinical and molecular diagnosis; thus, making genetic counseling and prenatal testing easier in future. Keywords: Limb malformation, syndactyly, digit webbing, molecular genetics.

Place Value of Chemotherapy during Pregnancy

Approximately, 1 in 1,000-2,000 pregnancies today is complicated by cancers such as Breast, Cervical, Lymphoma or Melanoma; whose treatment is centralized to Chemotherapy via certain cytotoxic and other drugs. BUT, IS CHEMOTHERAPY DURING PREGNANCY REALLY A WISE CHOICE? Depending upon the Impact of pregnancy on the outcome of cancer, Gestational age and risk of metastasis to the placenta and fetus, and Safety of treatment; chemotherapy is suggested which ironically, yields an increased risk of birth defects. Certain cancers like Hodgkin Lymphoma and Breast cancer can have their treatment delayed, until delivery by giving steroids and till the completion of first trimester, respectively. But Cervical and Melanoma cancers require an urgent treatment due to their high metastasis property. In cervical cancer, chemotherapy starts only after the termination of pregnancy as the Uterus itself gets affected. While in melanoma, Placenta and Fetus are the targets due to certain hormonal changes. The greatest risk to the fetus occurs during the first trimester as it is the Critical stage of its development, especially when chemotherapy involves anti-metabolite drugs. Such cytotoxic agents interrupt metabolic pathways by destroying macromolecules of tumor as well as of normal tissue, thereby interfering with DNA and RNA synthesis. As a result, it leads to systemic toxicity and teratogenicity. These conditions cause defects like ventriculomegaly, bicuspid aortic valve, high arched palate, limb malformations, necrotizing enterocolitis in the fetus. Moreover, there is also the risk of infection and hemorrhage caused by Myelosuppression chemotherapy that causes lowering in Red Blood Corpuscles, White Blood Corpuscles and Platelet count. Thus, in all such cancers and their therapies, the primary concern remains centralized – Exposure of fetus to the therapy and its wellbeing. There is a need to befit chemotherapy during the course of pregnancy at a place, where it acts as a boon for both the mother as well as the developing fetus.

Challenging Reproductive Genetic Counseling in Families at High Risk for Rare Genetic Syndromes – A Case Report with Possible Denys-Drash Syndrome

Calculating the recurrence risk is an integral part of everyday practice of the genetic counselor, but certain difficulties occur when explaining it to the parents of a child with a rare dysmorphic syndrome. We present a case of a family with first newborn with multiple anomalies and exitus letalis, registered on the second day. At birth, the baby presented with limb malformations. Additionally, a spontaneous pneumothorax, neonatal cerebral ischemia, and intraamniotic infection were diagnosed. A post-mortem examination revealed additional multiple internal malformations such as patent foramen ovale, bicornuate uterus, accessory spleen, bilateral adrenal hyperplasia, unilateral Wilm’s tumor of the left kidney, diffuse glomerular and interstitial fibrosis, and protein cylinders in dilated renal tubules. Standard GTG banding karyotyping showed a normal male karyotype 46,XY,16qh+ that did not correspond to the female phenotype of the patient’s genitalia. Postmortem findings together with sex phenotype/genotype discordance suggested Denys-Drash syndrome as possible diagnosis. Amplification of all exons but exon 9 of WT1 gene was not successful on DNA extracted from formalin-fixed paraffin-embedded tissue (FFPET) sample. Sanger sequencing of exon 9 did not reveal a causative mutation. In current case the severe neonatal presentation and absence of molecular conformation complicated giving a certain prognosis for the recurrence risk. Reproductive genetic counseling in families with rare genetic conditions could be very challenging.

An Isolated Case of Brachyphalangism of the Basal Finger Bones of the Little Finger with Symptoms of Tenosynovitis: A Case Report

Brachydactyly is a general term that refers to disproportionately short fingers and toes and forms a part of the group of limb malformations characterized by bone dysostosis. Brachydactyly usually occurs either as an isolated malformation or as a part of a complex malformation syndrome. Brachydactyly is classified as types A, B, C, D, or E; brachymetatarsus IV; Sugarman brachydactyly; or Kirner deformity. Various types of isolated brachydactyly are rare, except for types A3 and D. We describe a 15-year-old girl with isolated brachyphalangism of the basal finger bones of the little finger with symptoms of tenosynovitis. Tenosynovitis might be caused by growth deviation between the flexor digitorum superficialis and the flexor digitorum profundus. The patient responded very well to surgical treatment.

Brachdactyly Instigated as a Result of Mutation in GDF5 and NOG Genes in Pakistani Population.

Objectives:Brachdactyly a genetic disorder associated with the abnormal development of metacarpals, phalanges or both which results in the shortening of hands and feet. Mutations in the contributing genes has been recognized with the majority of the investigated syndromic form of brachdactyly. The current study was proposed to examine mutation in NOG and GDF5 genes in a Pakistani family.Methods:Poly Acrylamide Gel Electrophoresis and Polymerase Chain Reaction was used for the genomic screening and linkage analysis to observe the mutation in genes. The samples were collected from Luckki Marwat district, KPK, while the research study was conducted in the department of Biochemistry, Quaid-I-Azam University, Islamabad, Pakistan.Results:After survey, family was identified with brachdactyly type A2 and investigated a heterozygous arginine to glutamine exchange in the growth demarcation factor 5 in all the victim persons. Different types of skeletal dysplasia resulted due to mutation in the GDF5 genes. Novel GDF5 genes mutations were reported with distinct limb malformation and sequencing of coding region revealed that the mildly affected individuals were heterozygous while the harshly affected individuals were homozygous.Conclusion:The current study reported the genetic variability and concluded that the Brachdacytyly type A2 and type B2 resulted due to mutation in GDF5 and NOG genes respectively. A new subtype of brachydactyly (BDB2) was instigated as a result of novel mutations in NOG. The mutation has been reported for the first time in Pakistani population and especially in Pushtoon ethnic population.

Homozygous sequence variants in the WNT10B gene underlie split hand/foot malformation.

Split-hand/split-foot malformation (SHFM), also known as ectrodactyly is a rare genetic disorder. It is a clinically and genetically heterogeneous group of limb malformations characterized by absence/hypoplasia and/or median cleft of hands and/or feet. To date, seven genes underlying SHFM have been identified. This study described four consanguineous families (A-D) segregating SHFM in an autosomal recessive manner. Linkage in the families was established to chromosome 12p11.1–q13.13 harboring WNT10B gene. Sequence analysis identified a novel homozygous nonsense variant (p.Gln154*) in exon 4 of the WNT10B gene in two families (A and B). In the other two families (C and D), a previously reported variant (c.300_306dupAGGGCGG; p.Leu103Argfs*53) was detected. This study further expands the spectrum of the sequence variants reported in the WNT10B gene, which result in the split hand/foot malformation.

The regional anesthesia for surgical correction of the malformation of upper extremities in pediatric

The article presents an analysis of the publications devoted to the problems of anesthesia to surgical procedures at the malformations of the upper extremity in children. The article reviews the questions of epidemiology, classification of upper extremity malformation, safety of anesthesia and the role of regional blockades in the structure of intraoperative and postoperative analgesia to surgical procedures at the malformations of the upper extremity in children. Children are more likely than adults to experience stress in the operating room and early postoperative period. Children are almost impossible to prepare psychologically for the upcoming anesthesia, surgical intervention, a sense of pain after it. Surgical correction of malformations of the upper limbs in children is characterized by multistage and high traumatism, which requires the search for adequate methods of anesthesia, capable of ensuring not only the absence of pain, but also the negative impact on the nervous system of little patients. The key to the application of regional anesthesia in young children is the need for sedation or general anesthesia. The use of ultrasound navigation and electrostimulation of peripheral nerves significantly increases the level of safety and success of their realization. At present, the questions about the duration of postoperative analgesia with the use of peripheral nerve blocks and the need for additional anesthesia in the early postoperative period have been little studied. The influence of the applied anesthesia technique on the state of young children in the postoperative period are requires further investigation.

Association of VACTERL with truncus arteriosus, left-sided aortic arch, hypoplastic pulmonary arteries, and severe radial axis defect

Background: VACTERL association is usually a sporadic disorder, the possible etiologies of which have been proposed as familial as well as multiple genetic and environmental factors. VACTERL association usually consists of at least three of the core features of vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities. Vertebral anomalies, cardiac malformations, renal anomalies, and limb malformations have been reported to occur in 60-80%, 40-80%, 50-80%, and 40-50% of the patients, respectively. Among the cardiac anomalies, ventricular septal defect is the most prevalent one. Truncus arteriosus is a rarely associated defect. The radial anomalies are the most classic limb defects with different severity levels (types I-IV). Although radial axis defect usually accompanies this association, complete absence of radius is reported only in one third of the cases. Case report: In this case study, we reported a neonate having this association consisting of severe cyanotic congenital heart defect (truncus arteriosus) and unilateral type IV radial aplasia. Conclusion: VACTERL association components can have various new findings.

A novel homozygous missense mutation in BHLHA9 causes mesoaxial synostotic syndactyly with phalangeal reduction in a Pakistani family

Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) is a rare non-syndromic limb malformation with autosomal recessive inheritance. To date, only a few affected families with MSSD who had BHLHA9 mutations have been reported. The present report describes a consanguineous Pakistani family with five affected individuals with MSSD who exhibited an autosomal recessive pattern. Genotyping followed by Sanger sequencing was performed, and we identified a novel homozygous missense mutation (c.311T>C, p.Ile104Thr) in the BHLHA9 gene. This finding expands the spectrum of known mutations in the BHLHA9 gene that cause MSSD.

A Recurrent De Novo Nonsense Variant in ZSWIM6 Results in Severe Intellectual Disability without Frontonasal or Limb Malformations

A recurrent de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect. We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C>T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations. We show that the c.2737C>T variant does not trigger nonsense-mediated decay of the ZSWIM6 mRNA in affected individual-derived cells. This finding supports the existence of a truncated ZSWIM6 protein lacking the Sin3-like domain, which could have a dominant-negative effect. This study builds support for a key role for ZSWIM6 in neuronal development and function, in addition to its putative roles in limb and craniofacial development, and provides a striking example of different variants in the same gene leading to distinct phenotypes.

Orthopaedic manifestations within the 22q11.2 Deletion syndrome: A systematic review.

The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome with an estimated prevalence of 1:4,000 live births. 22q11.2DS is known to have wide phenotypic variability, including orthopaedic manifestations. The purpose of this systematic review is to increase the awareness of orthopaedic manifestations associated with 22q11.2DS. This systematic review was performed according to the PRISMA Guidelines. Original epidemiological studies on the prevalence of orthopaedic manifestations within 22q11.2DS were systematically searched for in PubMed and EMBASE. The included articles were scored according to a risk-of-bias tool, a best-evidence synthesis was performed and the prevalence data was extracted. Sixty-nine published manuscripts described 58 orthopaedic manifestations in a total of 6,055 patients. The prevalence of at least one cervical or occipital anomaly is 90.5-100% (strong evidence). Fourteen studies (n = 2,264) revealed moderate evidence for a wide scoliosis prevalence of 0.6-60%. Two studies demonstrated that 5-6.4% of all 22q11.2DS patients required surgical scoliosis correction. Fifteen studies (n = 2,115) reported a 1.1-13.3% prevalence of clubfoot with moderate evidence. Other reported orthopaedic manifestations are patellar dislocation (10-20%), juvenile rheumatic arthritis (3.75%), impaired growth and skeletal anomalies like polydactyly (1.0-3.7%), syndactyly (11-11.8%), butterfly vertebrae (11.1%) and 13 ribs (2-19%). Orthopaedic findings are important manifestations of the 22q11.2DS, both in bringing patients to diagnostic attention and in requiring surveillance and appropriate intervention. Data on these manifestations are scattered and incomprehensive. Routinely screening for cervical anomalies, scoliosis, and upper and lower limb malformations is recommended in this vulnerable group of patients.

Phenotypic and genotypic aspects of Townes-Brock syndrome: case report of patient in southern Brazil with a new SALL1 hotspot region nonsense mutation

BackgroundTownes-Brocks syndrome (TBS) is a rare autosomal dominant condition characterized by renal, anal, limb, and auditory abnormalities. TBS diagnosis can be challenging in settings where genetic analysis is not readily available. TBS traits overlap with those of Goldenhar and VACTERL syndromes.Case presentationHere, we present the case of a 5-year-old Brazilian boy born with an anorectal abnormality, limb and external ears malformations, genitourinary anomalies, and a congenital heart defect. Genetic analysis revealed a SALL1 nonsense mutation. The case is discussed in the context of the current literature.ConclusionsBecause of the variability in TBS clinical presentation, genetic analysis is key to the differential diagnosis of TBS relative to phenotypically similar syndromes.

Genetic Overview of Syndactyly and Polydactyly.

Summary:Syndactyly and polydactyly—respectively characterized by fused and supernumerary digits—are among the most common congenital limb malformations, with syndactyly presenting at an estimated incidence of 1 in 2,000–3,000 live births and polydactyly at a frequency of 1 in approximately 700–1,000 live births. Despite their relatively regular manifestation in the clinic, the etiologies of syndactyly and polydactyly remain poorly understood because of their phenotypic and genetic diversity. Further, even though concrete knowledge of genotypic links has been established for some variants of syndactyly and polydactyly, there appears to be no single comprehensive published summary of all syndromic and nonsyndromic syndactyly and polydactyly presentations, and there is decidedly no resource that maps all syndromic and nonsyndromic syndactylies and polydactylies to their genetic bases. This gap in the literature problematizes comprehensive carrier screening and prenatal diagnosis and complicates novel diagnostic attempts. This review thus attempts to collect all that is known about the genetic bases of syndromic and nonsyndromic syndactylies and polydactylies, as well as to highlight the dactyly manifestations for which no genetic bases are as yet known. Then, having established a summation of existing and missing knowledge, this work briefly outlines the diagnostic techniques that a genetics-reinforced understanding of syndactyly and polydactyly could inform.

Middle-aged individuals with thalidomide embryopathy have undergone few surgical limb procedures and demonstrate a high degree of physical independence.

BackgroundThalidomide is known to have induced thalidomide embryopathy (TE) in more than 10,000 live-born children worldwide between 1957–1962.AimThe aim of this study was to investigate the need for orthopaedic surgery and limb orthosis in relation to function and physical independence in middle-aged individuals with TE.Methods13 women/18 men with a mean age of 45.8 (SD 1.1) years were included. Information about limb surgery, the use of orthotic devices, jobs, accommodation, disability adjustments and personal assistants was collected. Physical function was measured by a modified general function score. The time needed for activities of daily living (ADL) was collected. Individuals with proximal focal femoral deficiency, PFFD, and participants in need of home or work adaptations were compared with the rest of the group.Result31 surgical procedures had been performed in the extremities. Three individuals were in need of personal assistance and seven had disability-adjusted homes. 28 individuals were working and 24 reported participation in exercises. Those with PFFD had significantly lower function score and needed a significantly longer time for ADL in the morning (p = 0.001 and p = 0.032). The group in need of home or work adjustments had significantly lower function score and needed longer time for morning ADL (p = 0.012 and p = 0.009).DiscussionFew orthopaedic procedures had been performed. The TE individuals except the ones with PFFD and those in the need of disability adjustments, were mostly active workers, reported good physical function and participated in exercises, despite limb malformations.