Fibular hemimelia and risk of patellar dislocations: A case series.

The likelihood of patellar instability and consequently, risk of patellar dislocations is higher in those with anatomical abnormalities. Fibular hemimelia is a congenital disorder resulting in partial or full absence of the fibula, often with absence of the lateral and cruciate ligaments, although this patient group rarely undergoes ligament reconstruction. There is potential for adverse outcomes, in the longer term, including, possible increased risk of patellar dislocation and pain in the knee and hip. We aim to investigate the potential risk of spontaneous, unprovoked patellar dislocation among patients with fibular hemimelia, through a review of medical records and radiological investigations. All patients with a diagnosis of fibular hemimelia were included (n = 25), regardless of ultimate approach to management. Tibiofemoral angle measurement and Caton-Deschamps indices were calculated where suitable radiology was available, to better establish extent of potential patellar instability. All the patients with normal Caton-Deschamps indices had only partial fibular absence, although this does not detract from absence or hypoplasia of the anterior cruciate ligament, as a risk factor for patellar dislocation by predisposing to anterior tibial translation. Notably, of the three patients with increased Caton-Deschamps indices, two had complete fibular absence and underwent definitive amputation surgery at age 18 months and 3 years, respectively. Ultimately, this was a young patient group and on-going follow-up might yield better understanding of knee stability. Maintaining a well-aligned lower limb throughout growth might be protective even in the presence of anatomical abnormalities. This article mainly aims to raise awareness among prosthetic and orthotic professionals regarding the increased risk of patella dislocations.

Specific deletion of Axin1 leads to activation of ß-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice.

Axin1 is a key regulator of canonical Wnt signaling pathway. Roles of Axin1 in skeletal development and in disease occurrence have not been fully defined. Here, we report that Axin1 is essential for lower limb development. Specific deletion of Axin1 in limb mesenchymal cells leads to fibular hemimelia (FH)-like phenotype, associated with tarsal coalition. Further studies demonstrate that FH disease is associated with additional defects in Axin1 knockout (KO) mice, including decreased osteoclast formation and defects in angiogenesis. We then provide in vivo evidence showing that Axin1 controls limb development through both canonical ß-catenin and BMP signaling pathways. We demonstrate that inhibition of ß-catenin or BMP signaling could significantly reverse the FH phenotype in mice. Together, our findings reveal that integration of ß-catenin and BMP signaling by Axin1 is required for lower limb development. Defect in Axin1 signaling could lead to the development of FH disease.

Amelia and phocomelia in Finland: Characteristics and prevalences in a nationwide population-based study.

BACKGROUND: Amelia and phocomelia represent severe limb reduction defects. Specific epidemiologic data on these defects are scarce. We conducted a descriptive analysis of prevalence data in Finland during 1993-2008 to clarify the epidemiology nationwide in a population-based register study. We hypothesized that increasing maternal age would affect the total prevalence of each disorder. MATERIALS AND METHODS: We collected information on all fetuses and infants affected by amelia and phocomelia during 1993-2008 from the National Register of Congenital Malformations in Finland. The clinical, laboratory, autopsy, and imaging data were re-evaluated where available for all cases found. RESULTS: A total of 23 amelia and 7 phocomelia patients were identified. Thalidomide was not an etiological factor in any of the cases. The total prevalence of amelia was 2.43 per 100,000 births. The live birth prevalence was 0.63 per 100,000 live births. The total prevalence of phocomelia was 0.74 per 100,000 births, and the live birth prevalence was 0.53 per 100,000 live births. Infant mortality in amelia and phocomelia was 67% and 60%, respectively. CONCLUSIONS: Infant mortality is high among amelia and phocomelia. Most cases had other major associated anomalies, but syndromic amelia cases were rare. Total prevalences were higher than previously reported and showed an increase in prevalence toward the end of the study period. The percentage of elective terminations of pregnancy for these disorders is high. While isolated cases are rare, they most likely present a better prognosis. Thus, correct diagnosis is essential in counseling for possible elective termination.

Sirenomelia: Review of a Rare Syndrome with Case Report, Review of Anatomy, and Thoughts on Management.

BACKGROUND: Sirenomelia is a rare syndrome in which the infant is born with the legs fused from the pelvis to the feet. Sirenomelia is often fatal in the neonatal period because of multiple other anomalies. The feet may be absent; if present, they are often splayed outward or face backward. There are no case reports of any patient with this syndrome who has been able to walk after separation of the legs. METHODS: The authors report on their patient with sirenomelia who was born with the feet facing backward but otherwise normal-appearing hips and thighs and no other anomalies that would lead to fatality in the near future. After preoperative tissue expansion, the authors performed separation of the legs with through-knee amputations, utilizing a vascularized flap from the lower part of the legs based on the sciatic vessels for coverage of the perineum. There was no need for skin grafts or dermal matrices and the patient was referred to physical therapy after recovery from surgery in an attempt to allow her to ambulate. RESULTS: The patient began to ambulate on her stumps early after surgical repair and is now walking with stubby prostheses. Her other medical issues have remained stable and nonproblematic. CONCLUSIONS: Selected patients with sirenomelia may be able to walk after separation of the legs, depending on the status of other congenital differences as well as the status of the legs when separated. Careful workup with multidisciplinary planning of overall care as well as surgical care is essential.

Laurin-Sandrow Syndrome: A Case Report and Review of Literature.

Laurin-Sandrow syndrome (LSS) is an extremely rare syndrome of mirror hand and leg with less than 20 cases reported in literature. The syndrome has been attributed to a mutation in the MIPOL-1 (mirror-image polydactyly) gene located on locus 14q13.3-q21 coding for CCDC193 (coiled-coli domain containing 193) protein. It is characterised by limb, facial and central nervous system anomalies with the most constant being fibular dimelia with fibular ray duplication, polydactyly with secondary deformities of fixed equinus, knee joint instability and flexion deformity. It is associated less frequently with ulnar dimelia, thumb aplasia/hypoplasia, ulnar ray duplication, symbrachypolydactyly, 'rosette' hands, facial dysmorphism like hypertelorism, broad columella and flat nose, CNS anomalies like aplasia/hypoplasia of corpus callosum, hydrocephalus and muscular dystonia. We report a 2-year-old male child with LSS and perform a literature review to expound on this rare syndrome. Level of Evidence: Level V (Therapeutic).

A rare case of radius hemimelia: a case report.

Radial dysplasia congenital defect resulting in shortening of the forearm due to congenital shortening of the radius. Isidore Geoffroy Saint-Hilaire coined the term "hemimelia" around 1836-1837. Affected individuals may also have reduced limb functions abnormalities of the soft tissues, vasculature of the forearm. The management consist of splinting, stretching, and centralization. Physical therapy management plays a vital role in regaining hand function and improving quality of life. In severe cases, surgical correction such as osteotomy. Radial hemimelia is a rare disorder with 1/5000-30,000 live birth. A 16-year-old girl was admitted to Acharya Vinoba Bhave Rural Hospital (AVBRH) with complaints of weakness of the right upper limb along with a tingling sensation from the past 1 year. She was operated on with ulnar osteotomy and physical therapy management was initiated which consists of regaining mobility and strength and making the patient functionally independent. We concluded that a well structure physical therapy protocol along with medical therapy post-surgery improved the overall status of the patient.

Postaxial hypoplasia of the lower extremity associated with congenital dislocation of the patella: A case report.

RATIONALE: Evaluation of clinical and radiologic abnormalities in patients with postaxial hypoplasia of the lower extremity (PHLE) for treatment decisions represents a major challenge, which is more complicated when PHLE is associated with congenital dislocation of the patella. PATIENT CONCERNS: : Herein, we present the case of an 8-year-old female patient with evident length inequality in her left lower extremity and inability to walk. DIAGNOSES: Radiological evaluation revealed PHLE with fibular hemimelia, proximal femoral focal deficiency, tarsal coalition, and congenital patellar dislocation of the patella. The right lower extremity was also affected by fibular hemimelia. INTERVENTIONS AND OUTCOMES: Surgical management included the Roux-Goldthwait technique for patellofemoral joint realignment, a medial knee stapled with Blount technique, and femur enlargement using the Wagner technique. The results from surgical intervention included a left femoral elongation of 6.7 cm featuring callus with angulation, displacement, and a discrepancy of 5 cm between femurs with a flexor contraction in the knee of -15° and a centralized knee. LESSON: PHLE accompanied by congenital dislocation of the patella has not been extensively described in the literature; therefore, there is no established management. Starting reconstruction at an early age, together with an adequate classification of the deformity, are essential factors when opting for limb reconstruction.

Fibular hemimelia.

Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and absent rays. A literature review showed only a handful of cases of prenatal diagnosis of fibular hemimelia. It is a rare disorder that might be isolated or associated with visceral anomalies.

Anesthetic management in an infant with tetra-amelia syndrome with congenital maxillomandibular fusion: A case report.

A 10-month-old girl who had tetra-amelia syndrome and congenital maxillomandibular fusion (syngnathia) was scheduled for the surgical fusion separation. Anesthetic management for this case was considerably challenging. Standard monitoring was still applied to the patient's extremities. IV access was suspected to be difficult but firmly needed before intubation to provide resuscitation during an emergency. Connecting anesthetic circuit with nasopharyngeal airway was the preferred technique due to its benefits such as maintaining spontaneous ventilation, providing inhaled anesthetic, as well as monitoring oxygenation and ventilation. Importantly, the cornerstones for handling such complicated cases are multidisciplinary approach and teamwork.

Congenital Limb Deficiency: A Case Report.

The complete absence of limbs is a rare occurrence. Though the causes are various, it is hard to elicit most of the time. They are usually diagnosed via anomaly scan but the lack of access to the same can often lead to a term presentation. It is still not uncommon to receive pregnant patients at term to the hospital or in labour as the first antenatal visit. Increasing the feasibility of the scan can help in the early diagnosis and management. Here, we report a rare combination of limb defects that we managed in a district-level hospital and highlight the difficulties in the management and referral of the patients while working in rural areas. Keywords: amelia; antenatal care; congenital limb deformities; fetal ultrasonography.

Proximal Femoral Focal Deficiency/Congenital Femoral Deficiency: Evaluation and Management.

Proximal focal femoral deficiency is a congenital transverse deficiency in which the femur is globally smaller with a typical proximal deformity at the hip that may include distal involvement of knees, leg, and feet. Congenital femoral deficiency (CFD) describes a broader spectrum of longitudinal deficiency inclusive of proximal focal femoral deficiency. CFD may also include lateral distal femoral hypoplasia, knee cruciate ligament deficiency, rotational instability, patellar dislocation, fibular hemimelia, ray absence, and contralateral limb involvement. Treatment intends to maximize function by limb equalization and deformity correction ranging from nonsurgical management using prosthetics to amputation and may include lengthening, shortening, and complex limb reconstruction. Management decisions depend on overall severity and the patient and family's preferences and priorities. Owing to its complexity, CFD is best treated by clinicians with considerable deformity treatment experience who can help guide decision making and embark on a treatment course that will maximize the functional outcome.

Six-month survival of a monochorionic monoamniotic twin with sirenomelia.

BACKGROUND: Sirenomelia is a congenital malformation of the lower body characterized by a single midline lower limb and severe urogenital and gastrointestinal malformations. Sirenomelia is rare (estimated incidence of approximately 1/100,000) and usually lethal in the perinatal period. CASE: A 2,042 g Japanese male infant, one of monochorionic monoamniotic twins, was born at 34 weeks of gestation by elective caesarean section. Sirenomelia was prenatally diagnosed. Single midline lower limb, bilateral dysplastic kidneys, an omphalomesenteric fistula, colon atresia, imperforate anus, indiscernible genital structures, and myelomeningocele were detected at birth. The amniotic fluid volume was normal throughout the pregnancy course, which led to appropriate lung maturation of the twin with sirenomelia. Although renal replacement therapy was initiated soon after birth, stable peritoneal dialysis was difficult because of the limited intraperitoneal space, and the infant frequently developed peritonitis. He died of sudden cardiorespiratory arrest at 6 months of age. Postmortem examination showed bilateral dysplastic kidneys, agenesis of the ureters and urinary bladder, abnormal branching and agenesis of the distal colon, bilateral inguinal hernias, and small testes. CONCLUSION: Infants with sirenomelia, even those with end-stage kidney disease at birth, may survive if they have a stable cardiorespiratory status at birth and renal replacement therapy is appropriately initiated.

Protetización temprana y seguimiento de paciente pediátrico con hemimelia tibial / Early Fitting and Follow-Up of A Pediatric Patient with Tibial Hemimelia

Introducción: La hemimelia tibial es una entidad poco frecuente, presente hasta en 1:1.000.000 nacidos vivos. Tiene una asociación genética autosómica recesiva, y se presenta con cambios en la morfología del miembro inferior con una tibia ausente o presente parcialmente, además de cambios en peroné, rodilla y pie. Según su clasificación se puede manejar con reconstrucción quirúrgica de la extremidad o amputación. La posibilidad de una prótesis temprana favorece el resultado funcional del paciente y su adaptación protésica. Objetivo: Presentar el caso de una entidad poco común tratada con desarticulación a nivel de la rodilla y prótesis por su grado de compromiso. Presentación de caso: Paciente femenina de tres años con compromiso del miembro inferior derecho. Los primeros años usó una prótesis artesanal fabricada por su familia. Fue valorada por la Junta Médica de rehabilitación y ortopedia que decidió intervención quirúrgica para desarticulación de la rodilla. Se realizó protetización temprana en busca de beneficios de cicatrización, control del edema y adaptación postquirúrgica. Se realizan controles posteriores con ajustes a la prótesis de acuerdo con las necesidades propias de la edad de la paciente. Conclusiones: Se muestra una adecuada evolución postquirúrgica, sin dolor o neuropatía, con un reinicio temprano de la marcha y progreso adecuado de su neurodesarrollo e integración social, lo que da una pauta de manejo en paciente pediátrico con este tipo de deformidades(AU)

Introduction: Tibial hemimelia is a rare entity, reported in up to 1:1,000,000 live births. It has an autosomal recessive genetic association, and it presents with changes in the morphology of the lower limb with an absent or partially present tibia, as well as changes in the fibula, knee, and foot. Depending on its classification, it can be managed with surgical reconstruction of the limb or amputation. The possibility of an early prosthesis favors the functional result of the patient and his prosthetic adaptation. Objective: To report the case of a rare entity treated with knee disarticulation and prosthesis due to its degree of compromise. Case report: The case of a three-year-old female patient with compromise of the lower right limb is reported here. The first years she used a handmade prosthesis made by her family. She was assessed by the Medical Board of Rehabilitation and Orthopedics, which decided to undergo surgery for knee disarticulation. Early fittings were performed in search of healing benefits, edema control and post-surgical adaptation. Subsequent controls were carried out with adjustments to the prosthesis according to the needs of the patient's age. Conclusions: An adequate post-surgical evolution is shown, without pain or neuropathy, with early resumption of gait and adequate progress of their neurodevelopment and social integration, which provides recommendation for management in pediatric patients with this type of deformity(AU)

"Laurin-Sandrow Syndrome - a review of the literature and classification system".

INTRODUCTION: Laurin-Sandrow syndrome also known as tetramelic mirror-image polydactyly is a rare congenital disorder characterized classically by polysyndactyly of the hands, mirror feet and nose anomalies (hypoplasia of the nasal alae and short columella) often associated with ulnar and/or fibular duplication. As a pathologic entity, it is heterogeneous, the patients displaying a variety of symptoms. This review aims to analyze the different aspects of the condition, such as clinical findings and methods of treatment to summarize the principal features of Laurin-Sandrow syndrome. MATERIALS AND METHODS: The review is based on searches on PubMed, Web of Science and Researchgate of the following terms: "Laurin-Sandrow syndrome", "mirror hands", "mirror feet", "tetramelic mirror-image polydactyly", "fibular dimelia" and "ulnar dimelia". Clinical cases, reviews and original articles were included. RESULTS: As a consequence of our findings, we suggest a modification of the Al-Qattan classification system for Mirror Hand-Multiple Hand Spectrum. CONCLUSION: Even though it has an extremely low incidence, a thorough understanding of the syndrome enables the surgeon to choose the appropriate treatment with the ultimate goal to improve the patient's life quality.

Esco2 and cohesin regulate CRL4 ubiquitin ligase ddb1 expression and thalidomide teratogenicity.

Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) are severe developmental maladies that arise from mutation of cohesin (including SMC3, CdLS) and ESCO2 (RBS). Though ESCO2 activates cohesin, CdLS and RBS etiologies are currently considered non-synonymous and for which pharmacological treatments are unavailable. Here, we identify a unifying mechanism that integrates these genetic maladies to pharmacologically-induced teratogenicity via thalidomide. Our results reveal that Esco2 and cohesin co-regulate the transcription of a component of CRL4 ubiquitin ligase through which thalidomide exerts teratogenic effects. These findings are the first to link RBS and CdLS to thalidomide teratogenicity and offer new insights into treatments.

Prenatal diagnosis of Roberts syndrome in a Chinese family based on ultrasound findings and whole exome sequencing: a case report.

BACKGROUND: Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by variations in the ESCO2 gene; however, prenatal diagnosis of RBS has never been reported in Chinese families. Additionally, fetal-specific phenotypic characteristics associated with ESCO2 variants have not been reported. CASE PRESENTATION: A fetus in a healthy, nonconsanguineous Chinese family with multiple serious congenital malformations was diagnosed prenatally. Two consecutive fetuses in this family presented with tetraphocomelia, growth restriction, cleft lip and palate bilaterally, and other abnormalities. The main phenotypic characteristics of this case were strongly suspected to be associated with RBS. Finally, whole exome sequence analysis revealed the insertion of a homozygous base pair in exon 6 of the ESCO2 gene (NM_001017420.3, c.1111insA, NP_001017420.1, p.Thr371fs). Both of the couples were heterozygous carriers for this variant. CONCLUSION: We are the first to report a prenatal case of RBS diagnosed in a Chinese family. Here, we have confirmed that the rare variant is a definite pathogenic variant, and we provide detailed phenotypic characteristics for the prenatal diagnosis of RBS due to this causative variant.

Pseudo-Roberts Syndrome: An Entity or Not?

Background: Roberts syndrome is a genetic disorder characterized by tetra-phocomelia with abnormalities of ESCO2. We report a male stillborn with tetra-phocomelia and no ESCO2 mutation. Case report: Pre- and post-natal imaging and autopsy findings included schizencephaly, phocomelia of four limbs, micrognathia, oligodactyly, and cardiopulmonary malformations. Microcephaly on pre-natal imaging was not confirmed by autopsy examination. Karyotype, prenatal chromosome microarray and ESCO2 gene testing were normal. Conclusion: Given the various skeletal anomalies found on autopsy and imaging evaluations, at least phenotypically, our case appeared to conform into Roberts syndrome spectrum. Since the infant did not have the mutation associated with this disorder, this infant could be labeled as the first report of a pseudo-Roberts syndrome because many of his phenotypic anomalies are characteristic of Roberts syndrome in absence of the ESCO2 gene mutation.

Physical performance of children with longitudinal fibular deficiency (fibular hemimelia).

PURPOSE: Longitudinal fibular deficiency (LFD) is the most common congenital long bone deficiency. This study aimed to objectively assess the physical performance of children and adolescents with LFD compared with unaffected peers, and to examine trends over age for subgroups of the LFD population. METHODS: Differences between children with LFD and unaffected peers were examined with hand-held dynamometry for lower-limb muscle strength, Six-Minute Walk Test, Timed up and down stairs test, Star Excursion Balance Test, and Standing long jump. RESULTS: Thirty-nine children with LFD and 284 unaffected peers participated. Children with LFD performed at a lower level than their unaffected peers, on all measures of physical performance (mean 2.1 z-scores lower, all p < 0.01), except in long jump (p = 0.27). When comparing the performance of children with LFD to their unaffected peers across four age groups, there was a significant between-groups difference on all strength measures, and on the Six-Minute Walk distance, between children with and without LFD. These differences were smallest in young children (3-6 years) and largest in the older children (15-18 years) (all p < 0.01). Children with no lengthening surgery performed better on the Six-Minute Walk Test, covering a greater distance during the test, than those who had surgery (mean difference 83 metres, p < 0.01). There were no significant differences between children who had or had not undergone an amputation. CONCLUSIONS: Children with LFD performed at a significantly lower level than unaffected peers on all measures of physical performance other than jumping. The largest differences were in older children. This paper provides baseline functional data for future interventions in LFD. LEVEL OF EVIDENCE: Cross-sectional study.Implications for RehabilitationThis paper provides the first baseline functional data using validated objective measures on a consecutive cohort of children and adolescents with longitudinal fibular deficiency.Children with LFD performed significantly worse than their unaffected peers on all measures of physical performance other than jumping, with children falling further behind their peers as they age.Children who undergo an amputation typically have the most severe anatomical presentation and yet perform at an equivalent functional level.This paper identifies multiple modifiable impairments that represent potential opportunities for rehabilitation professionals to target with conservative treatment options to improve functional performance.