Multifaceted Hoxa13 function in urogenital development underlies the Hand-Foot-Genital Syndrome.

Hand-Foot-Genital syndrome is a rare condition caused by mutations in the HOXA13 gene and characterized by limb malformations and urogenital defects. While the role of Hoxa13 in limb development has been extensively studied, its function during the development of the urogenital system remains elusive mostly due to the embryonic lethality of Hoxa13 homozygous mutant mice. Using a conditional inactivation strategy, we show that mouse fetuses lacking Hoxa13 function develop megaureters, hydronephrosis and malformations of the uterus, reminiscent of the defects characterizing patients with Hand-Foot-Genital syndrome. Our analysis reveals that Hoxa13 plays a critical role in Müllerian ducts fusion and in ureter remodeling by regulating the elimination of the caudal common nephric duct, eventually preventing the separation from the nephric duct. Our data also reveal a specific role for Hoxa13 in the urogenital sinus, which is in part mediated by Gata3, as well as Hoxa13 requirement for the proper organization of the ureter. Finally, we provide evidence that Hoxa13 provides positional and temporal cues during the development of the lower urogenital system, a sine qua non condition for the proper function of the urinary system.

Epilepsy in Nicolaides-Baraitser Syndrome: Review of Literature and Report of 25 Patients Focusing on Treatment Aspects.

Nicolaides-Baraitser syndrome (NCBRS), caused by a mutation in the SMARCA2 gene, which goes along with intellectual disability, congenital malformations, especially of face and limbs, and often difficult-to-treat epilepsy, is surveyed focusing on epilepsy and its treatment. Patients were recruited via "Network Therapy of Rare Epilepsies (NETRE)" and an international NCBRS parent support group. Inclusion criterion is NCBRS-defining SMARCA2 mutation. Clinical findings including epilepsy classification, anticonvulsive treatment, electroencephalogram (EEG) findings, and neurodevelopmental outcome were collected with an electronic questionnaire. Inclusion of 25 NCBRS patients with epilepsy in 23 of 25. Overall, 85% of the participants (17/20) reported generalized seizures, the semiology varied widely. EEG showed generalized epileptogenic abnormalities in 53% (9/17), cranial magnetic resonance imaging (cMRI) was mainly inconspicuous. The five most frequently used anticonvulsive drugs were valproic acid (VPA [12/20]), levetiracetam (LEV [12/20]), phenobarbital (PB [8/20]), topiramate (TPM [5/20]), and carbamazepine (CBZ [5/20]). LEV (9/12), PB (6/8), TPM (4/5), and VPA (9/12) reduced the seizures' frequency in more than 50%. Temporary freedom of seizures (>6 months) was reached with LEV (4/12), PB (3/8), TPM (1/5, only combined with PB and nitrazepam [NZP]), and VPA (4/12). Seizures aggravation was observed under lamotrigine (LTG [2/4]), LEV (1/12), PB (1/8), and VPA (1/12). Ketogenic diet (KD) and vagal nerve stimulation (VNS) reduced seizures' frequency in one of two each. This first worldwide retrospective analysis of anticonvulsive therapy in NCBRS helps to treat epilepsy in NCBRS that mostly shows only initial response to anticonvulsive therapy, especially with LEV and VPA, but very rarely shows complete freedom of seizures in this, rather genetic than structural epilepsy.

Anaesthesia and orphan disease: management of a case of Nicolaides-Baraitser syndrome undergoing cleft palate surgery.

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a rare disease caused by mutations in the SMRCA2 gene, which affects chromatin remodelling and leads to a wide range of symptoms including microcephaly, distinct facial features, recurrent seizures, and severe mental retardation. Until now, less than 100 cases have been reported. CASE PRESENTATION: A 22-month old male infant with NCBRS underwent elective cleft palate surgery. The anaesthetists were challenged by the physiological condition of the patient: narrow face, very small mouth, mild tachypnea, slight sternal retractions, physical signs of partial monosomy 9p, and plagiocephalus, midface hypoplasia, V-shaped cleft palate, enhanced muscular hypotension, dysplastic kidneys (bilateral, estimated GFR: approx. 40 ml/m2), nocturnal oxygen demand, and combined apnea. In addition, little information was available about interaction of the NCBRS displayed by the patient and anaesthesia medications. CONCLUSIONS: The cleft palate was successfully closed using the bridge flap technique. Overall, we recommend to perform a trial video assisted laryngoscopy in the setting of spontaneous breathing with deep inhalative anaesthesia before administration of muscle relaxation to detect any airway difficulties while remaining spontaneoues breathing and protective reflexes.

A point mutation in Fgf9 impedes joint interzone formation leading to multiple synostoses syndrome.

Human multiple synostoses syndrome (SYNS) is an autosomal dominant disorder characterized by multiple joint fusions. We previously identified a point mutation (S99N) in FGF9 that causes human SYNS3. However, the physiological function of FGF9 during joint development and comprehensive molecular portraits of SYNS3 remain elusive. Here, we report that mice harboring the S99N mutation in Fgf9 develop the curly tail phenotype and partially or fully fused caudal vertebrae and limb joints, which mimic the major phenotypes of SYNS3 patients. Further study reveals that the S99N mutation in Fgf9 disrupts joint interzone formation by affecting the chondrogenic differentiation of mesenchymal cells at the early stage of joint development. Consistently, the limb bud micromass culture (LBMMC) assay shows that Fgf9 inhibits mesenchymal cell differentiation into chondrocytes by downregulating the expression of Sox6 and Sox9. However, the mutant protein does not exhibit the same inhibitory effect. We also show that Fgf9 is required for normal expression of Gdf5 in the prospective elbow and knee joints through its activation of Gdf5 promoter activity. Signal transduction assays indicate that the S99N mutation diminishes FGF signaling in developmental limb joints. Finally, we demonstrate that the conformational change in FGF9 resulting from the S99N mutation disrupts FGF9/FGFR/heparin interaction, which impedes FGF signaling in developmental joints. Taken together, we conclude that the S99N mutation in Fgf9 causes SYNS3 via the disturbance of joint interzone formation. These results further implicate the crucial role of Fgf9 during embryonic joint development.

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

BACKGROUND: Carbohydrate 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 proteoglycan in cartilage, and its sulfation is important in the developing growth plate of cartilage. A homozygous deletion encompassing part of the gene and the embedded miRNA MIR3922 had been detected in a woman with hand/foot malformation and malignant lymphoproliferative disease. Chst11-deficient mouse has severe chondrodysplasia, congenital arthritis and neonatal lethality. We searched for the causative variant for the unusual combination of limb malformations with variable expressivity accompanied by skeletal defects in a consanguineous Pakistani kindred. METHODS: We performed detailed clinical investigations in family members. Homozygosity mapping using SNP genotype data was performed to map the disease locus and exome sequencing to identify the underlying molecular defect. RESULTS: The limb malformations include brachydactyly, overriding digits and clino-symphalangism in hands and feet and syndactyly and hexadactyly in feet. Skeletal defects include scoliosis, dislocated patellae and fibulae and pectus excavatum. The disease locus is mapped to a 1.6 Mb region at 12q23, harbouring a homozygous in-frame deletion of 15 nucleotides in CHST11. Novel variant c.467_481del (p.L156_N160del) is deduced to lead to the deletion of five evolutionarily highly conserved amino acids and predicted as damaging to protein by in silico analysis. Our findings confirm the crucial role of CHST11 in skeletal morphogenesis and show that CHST11 defects have variable manifestations that include a variety of limb malformations and skeletal defects.

Management of pediatric foot deformities: an imaging review.

Abnormalities of foot alignment can be a cause of significant morbidity in children, and some require complex surgical intervention to improve functionality and decrease pain. Imaging plays a key role in management decisions. We address some of the most common surgical strategies for selected diagnoses including pes planus, congenital vertical talus, pes cavus, and clubfoot, with a focus on imaging findings.

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.

Hallux valgus and metatarsus adductus measurements: inter-reader reliability and correlations on radiographs and MRI.

AIM: To assess inter-reader reliability of metatarsus adductus (MA) using the traditional method and Engel's angle (EA) on radiography and magnetic resonance imaging (MRI) and assess correlations with hallux valgus (HV). METHODS AND MATERIALS: Ninety consecutive patients with radiographs and MRI of the foot were included. Two readers measured HV angle (HVA), traditional metatarsus adductus angle (MAA), and EA on radiographs and HVA and EA on MRI. Three- and two-way mixed model analyses were used for reader agreements. Ninety-five percent bootstrap confidence intervals were calculated. The linear mixed model was used for association between HVA and EA/MAA. RESULTS: Mean age and male to female ratio was 54.2±15.4 and 0.4:1, respectively. Mean HVA and EA were 20.6±9.4 and 21.2±8, 21.2±8.3 and 22.4±7.5 on radiographs and MRI, respectively. Mean MAA was 18.5±5.7 on radiographs. Inter-reader agreement was good for EA (ICC=0.73, 0.6) and moderate for MAA (ICC=0.41). Positive correlations between HVA, MAA, and EA on radiographs and MRI were found, but none were statistically significant (p=0.44 and 0.87). CONCLUSION: Engel's angle is more reproducible. Although positive correlations exist between the degrees of HV and MA, they are not statistically significant.

The role of objective facial analysis using FDNA in making diagnoses following whole exome analysis. Report of two patients with mutations in the BAF complex genes.

The genetic basis of numerous intellectual disability (ID) syndromes has recently been identified by applying exome analysis on a research or clinical basis. There is significant clinical overlap of biologically related syndromes, as exemplified by Nicolaides-Baraitser (NCBRS) and Coffin-Siris (CSS) syndrome. Both result from mutations affecting the BAF (mSWI/SNF) complex and belong to the growing category of BAFopathies. In addition to the notable clinical overlap between these BAFopathies, heterogeneity exists for patients clinically diagnosed with one of these conditions. We report two teenagers with ID whose molecular diagnosis of a SMARC2A or ARID1B mutation, respectively, was established through clinical exome analysis. Interestingly, using only the information provided in a single clinically obtained facial photograph from each patient, the facial dysmorphology analysis detected similarities to facial patterns associated with NCBRS as the first suggestion for both individuals, followed by CSS as the second highest ranked in the individual with the ARID1B mutation. Had this information been available to the laboratory performing the exome analysis, it could have been utilized during the variant analysis and reporting process, in conjunction with the written summary provided with each test requisition. While the available massive parallel sequencing technology, variant calling and variant interpretation are constantly evolving, clinical information remains critical for this diagnostic process. When trio analysis is not feasible, additional diagnostic tools may become particularly valuable. Facial dysmorphology analysis data may supplement the clinical phenotype summary and provide data independent of the clinician's personal experience and bias. © 2016 Wiley Periodicals, Inc.

"Coxa pedis" today.

UNLABELLED: Coxa pedis is the talocalcaneonavicular joint and is the distal enarthrosis of the lower limb. It is defined coxa because of: (1) the enarthrosic meaning from an anatomical point of view, (2) the analogy to the hip. The stabilising devices are structural, passive and active; the corresponding pathology is the "Coxa pedis destabilising syndrome". During walking, release and stiffening of the foot are related to the opening and closure of the kinetic chain of the coxa pedis: it is mutually reversible, while opening is a passive event, closure is an active one. Considering the importance of the flexor digitorum longus muscle in stabilising the coxa pedis, is it logical transferring it in the tibialis posterior disfunction? During walking, opening and closure of the kinetic chain of the coxa pedis intervene in the opening and closure of the kinetic chain of the entire lower limb. The kinetic chain closes starting from the bottom and moving upwards in the foot-knee-hip progression, and opens starting from the top and moving downwards. Even rotations along the orthogonal plane of the segmental axes of the limb contribute to the closure of the kinetic chain, coxa pedis dysmorphism (cavovalgus foot: false flat foot) can cause, during growth, dysmorphism of the hip (residual anteversion) and of the knee (condyles or tibial tuberosity) instead of the reverse. ISSUES: subtalar joint; anomalous subtalar pronation syndrome; flexor digitorum longum transfer pro tibialis posterior tendon; coxa pedis actor or participant in the functional integration of the lower limb; anterior knee pain syndrome.

Myogenic bladder defects in mouse models of human oculodentodigital dysplasia.

To date, over 65 mutations in the gene encoding Cx43 (connexin43) have been linked to the autosomal-dominant disease ODDD (oculodentodigital dysplasia). A subset of these patients experience bladder incontinence which could be due to underlying neurogenic deterioration or aberrant myogenic regulation. BSMCs (bladder smooth muscle cells) from wild-type and two Cx43 mutant lines (Cx43(G60S) and Cx43(I130T)) that mimic ODDD exhibit a significant reduction in total Cx43. Dye transfer studies revealed that the G60S mutant was a potent dominant-negative inhibitor of co-expressed Cx43, a property not equally shared by the I130T mutant. BSMCs from both mutant mouse strains were defective in their ability to contract, which is indicative of phenotype changes due to harbouring the Cx43 mutants. Upon stretching, Cx43 levels were significantly elevated in controls and mutants containing BSMCs, but the non-muscle myosin heavy chain A levels were only reduced in cells from control mice. Although the Cx43(G60S) mutant mice showed no difference in voided urine volume or frequency, the Cx43(I130T) mice voided less frequently. Thus, similar to the diversity of morbidities seen in ODDD patients, genetically modified mice also display mutation-specific changes in bladder function. Furthermore, although mutant mice have compromised smooth muscle contraction and response to stretch, overriding bladder defects in Cx43(I130T) mice are likely to be complemented by neurogenic changes.

Influence of a metatarsus adductus foot type on plantar pressures during walking in adults using a pedobarograph.

Metatarsus adductus is a relatively common congenital foot deformity that is often unrecognized at birth. Thus, the adult foot with metatarsus adductus is prone to pathologic entities that have been theorized to result from lateral column overload. We present a descriptive study comparing plantar foot pressure distribution during gait in subjects with and without metatarsus adductus. A total of 65 subjects were recruited for the study: 28 subjects with and 37 subjects without metatarsus adductus. An EMED(®) pedobarograph was used to collect the data. The analysis of the peak pressure and pressure-time integral in each of the 8 regions of the plantar surface of the foot showed significant (p < .05) differences between each of the regions and a significant (p < .05) interaction effect between the 8 regions and the 2 groups. A series of independent Student's t tests were therefore performed to determine which of the plantar regions showed a significant difference between the 2 groups. The result of those t tests showed that the peak pressure and pressure-time integral were significantly different (p < .05) between the 2 groups for the "heel," "lateral midfoot," and "lateral forefoot." The results of the present study support the concept that during gait, the adult foot with metatarsus adductus has increased peak plantar pressures on the lateral side of the foot.

Clinical and descriptive genetic study of polydactyly: a Pakistani experience of 313 cases.

Polydactyly, a common hereditary condition with additional digits in hands and/or feet, is a very attractive model to appreciate clinical and genetic heterogeneity. In order to get an insight into its phenotypic manifestations, we ascertained a cohort of 313 independent families with polydactyly from Pakistan; 35% cases turned out to be familial while 65% were sporadic. In majority of the index cases, polydactyly was presented as an isolated digit defect. Preaxial polydactyly types were 48.24% and postaxial were 51.8%. Familial polydactylies mainly had bilateral and symmetrical presentations, whereas sporadic cases were mostly unilateral and less often symmetrical. In the 313 index subjects a total of 508 limbs with additional digits were recorded. Variable expression was evident as the involvement of upper limbs was more common than the lower, right hand than the left, and left foot than the right. The present cohort establishes interesting epidemiological attributes of polydactyly in the Pakistani population and highlights its extraordinary clinical heterogeneity. Molecular analyses of this cohort are anticipated to elucidate novel genetic factors involved in the origin of additional digits in the growing limb and may provide clues to the role of stochastic factors in the etiology of phenotypic variability in polydactyly.

Resistant metatarsus adductus: prospective randomized trial of casting versus orthosis.

BACKGROUND: Metatarsus adductus is a common pediatric foot deformity related to intrauterine molding. It is usually a mild deformity that responds well to simple observation or minimal treatment with a home program of stretching. Resistant cases may need a more aggressive approach such as serial casting or special bracing to avoid the need for surgical intervention. We compared clinical outcomes using serial casting with orthoses for resistant metatarsus adductus. METHODS: We prospectively treated 27 infants (43 feet) between the ages 3 and 9 months who failed home stretching treatment. Patients were randomized to either serial plaster casting or Bebax orthoses. Footprints and simulated weight-bearing anteroposterior and lateral view radiographs were made at entry and follow-up. RESULTS: There was no statistical difference between casting and Bebax for the following parameters: age at study entry, length of treatment, number of clinic visits, follow-up, and follow-up maintenance treatments. Both groups showed improvement in footprint and radiographic measurements post-treatment, without worsening of heel valgus. The Bebax group had greater improvement in the footprint heel bisector measurement than the casting group. The Bebax treatment requires more active parental cooperation. A simulated cost analysis of materials and office visit charges, however, revealed that Bebax treatment was significantly less expensive, about half the cost of casting. CONCLUSION: Because of the cost savings and virtually identical clinical results, we recommend the Bebax orthosis for resistant metatarsus in pre-walking infants with parents who are compliant. Other considerations include specific insurance plans, which may pay for casts but not orthoses.

Congenital hyper-extension with subluxation of the knees - report of 2 cases.

Congenital dislocation of the knee popularly known as genu recurvatum; is a very rare condition, about 0.45% of all congenital anomalies. Furthermore isolated genu recurvatum is extremely rare because 60% of this condition is associated with other congenital anomalies. Congenital dislocation of hip is the commonest associated anomaly. Two babies 1 male and 1 female were born with severe hyperextension deformity of the knees about 30° degrees. Clinically and radiologically they were diagnosed as isolated genu recurvatum due to congenital dislocation of the knees. Gentle manipulation in the form of passive stretching and knee flexion was started at first day of life. The deformity of male and female baby was corrected in 34 and 30 days respectively. The babies were moving the knees and lower limbs normally at final follow up at 6 months follow up and were confirmed clinically and radiologically. Early recognition and immediate manipulation cures the condition fully in short time without operation.

Congenital heart defects in oculodentodigital dysplasia: Report of two cases.

Oculodentodigital dysplasia is caused by mutations in the GJA1 gene. Oculodentodigital dysplasia presents with a spectrum of clinical features including craniofacial, ocular, dental, and limb anomalies. Although recent findings implicate the major role of GJA1 during cardiac organogenesis, congenital heart defects are infrequently reported in oculodentodigital dysplasia. Here we report on two patients with GJA1 mutations presenting with cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis. The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2 presented at 6 months with a ventricular septal defect. The child had hypoplastic alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients underscore the importance of cardiac evaluations as part of the initial workup for patients with findings of oculodentodigital dysplasia. Conversely, those patients with type III syndactyly and congenital heart defect should be screened for GJA1 mutations.

Taylor spatial frame in severe foot deformities using double osteotomy: technical approach and primary results.

PURPOSE: The treatment of severe foot deformities in children or adolescents is complex and demanding to the surgeon. This paper describes the technical strategy of using a Taylor spatial frame and reports on the functional outcome. METHODS: The Taylor spatial frame was used by a single surgeon in patients with severe foot deformities. Seven patients with eight severe deformities were treated. Mean patient age at surgery was 15.1 (9-29) years. A double Taylor spatial frame reconstruction was mounted to the limb. All patients had a midtarsal osteotomy and an additional inverse dome-shaped calcaneus osteotomy. Assessed measures were pre- and postoperative deformity and associated complications and clinical results according to Ferreira et al. RESULTS: Mean follow-up was 576.5 (359-987) days. The final functional outcome according to Ferreira was good in seven cases, fair in none, and poor in one. Early complications included pin-tract infection, temporary hypoesthesia, and temporary shortening of the tendon of the M. flexor digitorum. At follow-up there was no deformity recurrence. CONCLUSION: In children or adolescents, the innovative treatment using the Taylor spatial frame and a double osteotomy allows joint-preserving correction of severe foot deformities. However, the complication rate is relatively high due to the severely deformed feet. Furthermore, the Taylor spatial frame is expensive. Thus, this treatment is only recommended for severe foot deformities and should be handled by experienced orthopedic surgeons.

Ray reduction of the foot in the treatment of macrodactyly and review of the literature.

Macrodactyly of the foot is a rare disorder characterized by enlargement of the soft tissue and osseous elements of the foot that impedes the development of normal function and gait. Despite the morbidity associated with this condition, many surgeons are reluctant to perform surgical reduction. In the present report, we describe 3 pediatric patients with pedal macrodactyly, who underwent surgical correction consisting of amputation of the most enlarged ray, reduction of the adjacent rays, and ray transposition, combined with debulking of soft tissues. All 3 patients subsequently developed a normal gait and were able to wear normal, or minimally adjusted, shoes. We advocate early surgical treatment of macrodactyly of the foot to enhance the development of normal function and gait.

Brachyphalangy, polydactyly and tibial aplasia/hypoplasia syndrome (OMIM 609945): case report and review of the literature.

Brachyphalangy, polydactyly and tibial aplasia/hypoplasia syndrome (OMIM 609945) is a rare congenital disorder. Only seven patients have been reported to date, and the etiology of this syndrome is unknown. Autosomal dominant inheritance with variable expression has been suggested based on the presence of minor features in some parents and the fact that neither parental consanguinity nor pairs of affected siblings were observed. We report on the first patient with this syndrome who was born to consanguineous parents. Neither the mother nor the father, who were first cousins, had clinical features suggestive of a manifestation of brachyphalangy, polydactyly and tibial aplasia/hypoplasia syndrome. The patient had no siblings, and the family history was unremarkable. Clinical problems included brachydactyly of hands and feet, splaying of fingers and toes, preaxial polydactyly of feet, bilateral tibial aplasia, shortened radius and ulna, and characteristic facial dysmorphic signs. The detailed description of this patient adds to our knowledge of the clinical manifestations of brachyphalangy, polydactyly and tibial aplasia/hypoplasia syndrome and will eventually also contribute to the elucidation of the underlying gene defects.

One-stage metatarsal lengthening by allograft interposition: a novel approach for congenital brachymetatarsia.

BACKGROUND: Congenital brachymetatarsia, a shortened metatarsal bone, can be corrected surgically by callus distraction or one-stage lengthening using bone graft. QUESTIONS/PURPOSES: We asked whether one-stage metatarsal lengthening using metatarsal homologous bone graft could improve forefoot function, lead to metatarsal healing, restore metatarsal parabola, and improve cosmetic appearance. PATIENTS AND METHODS: We retrospectively reviewed 29 patients (41 feet) in whom we lengthened 50 metatarsals. Surgery consisted of a transverse proximal osteotomy of the metatarsal shaft and interposition of a metatarsal homologous bone graft (average, 13 mm long) fixed with an intramedullary Kirschner wire. Minimum followup was 3 years (mean, 5 years; range, 3-11 years). RESULTS: Bone union was achieved in all cases. The mean preoperative American Orthopaedic Foot and Ankle Society score was 37 points (range, 28-53 points) and the mean postoperative score was 88 points (range, 74-96 points), with an average improvement of 51 points. Radiographically, the mean gain in length was 13 mm (range, 10-15 mm), and the mean percentage increase was 23%. CONCLUSIONS: One-stage metatarsal lengthening using interposition of metatarsal homologous bone graft to correct congenital brachymetatarsia has low morbidity for the patient, limited complications, short recovery times, and restores forefoot anatomy. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.