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INTRODUCTION AND IMPORTANCE: Polydactyly of the hand is a common anomaly among pediatrics, which can present in conjugation with other syndromes or on its own. Various types can be seen, ranging from the involvement of skin only to a completely formed digit. We report the first case of pacifier type thumb duplication presenting with VACTERL association. Herein, we also summarize the existing literature of the distinctive features and management of pacifier polydactyly. CASE PRESENTATION: A premature male infant with intrauterine growth restriction due to maternal type II diabetes was referred for a soft tissue attachment to the left hand. The infant showed VACTERL association signs, including a single kidney, small atrial septal defect, and ventricular septal defect. Examination revealed preaxial polydactyly with a cystic swelling connected to the palm. CLINICAL DISCUSSION: Preaxial polydactyly is the second most common congenital hand anomaly, and its pathology is thought to involve the disruption of apoptosis during embryonic development. Pacifier-type polydactyly is a unique variation characterized by severe edema of the soft tissue digit, believed to be caused by physical damage in utero. The case presented did not require surgical intervention as the duplicated thumb underwent spontaneous autoamputation as opposed to other cases in the literature. CONCLUSION: This is the first reported case of pacifier-type thumb duplication in a patient with VACTERL association. The presentation of this condition adds to the existing body of literature on VACTERL association. Surgical removal is the treatment of choice for pacifier polydactyly, but spontaneous resolution can occur.

RESUMEN

Townes-Brocks syndrome (TBS) is a rare syndrome characterized by triad of anal, ear, and thumb anomalies. Further malformations/anomalies include congenital heart diseases, foot malformations, sensorineural and/or conductive hearing impairment, genitourinary malformations, and anomalies of eye and nervous system. Definitive diagnosis for TBS is confirmed by molecular analysis for mutations in the SALL1 gene. Only one known case of TBS with absent pulmonary valve syndrome (APVS) has been previously described to our knowledge. Here, we report a newborn diagnosed with TBS with APVS and tetralogy of Fallot (TOF) who was found to carry the most common pathogenic SALL1 gene mutation c.826C > T (p.R276X), with its surgical repair and postoperative follow-up. To our knowledge, this is the first genotyped case of TBS from Turkey to date. TBS should be suspected in the presence of ear, anal, and thumb malformations in a neonate. If a patient with TBS and TOF-APVS needs preoperative ventilation within the first months of life, this implies prolonged postoperative intubation and increased risk of mortality.

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BACKGROUND: The relationship between maternal age (MA) and birth defects (BD) has been extensively studied while much less research, mostly with discordant results, has focused on the risk of paternal age (PA) for BD. Furthermore, no consensus has been reached on the best way to control the association of PA with MA. OBJECTIVES: The aim of the study was to evaluate the risk of PA increase, at 1-year intervals, for selected BD, especially controlling for the confounding effect of MA. METHODS: The sample comprised of 27,944 liveborns presenting 1 of 18 selected isolated BD. Conditional logistic regressions were applied to evaluate the risk of advanced PA and its yearly increase, adjusting by MA and other variables. RESULTS: Of the 18 analyzed BD, only the risk for preaxial polydactyly (PreP) showed a significant association with increasing PA, while advanced MA was of low risk. For esophageal and anal atresia, associations with both PA and MA increases were observed. CONCLUSIONS: Results support the hypothesis of advanced PA as a risk factor for PreP and helps clarify the so far unexplained nonrandom association between this defect and Down syndrome.

Asunto(s)

Ano Imperforado , Edad Paterna , Polidactilia , Humanos , Masculino , Ano Imperforado/epidemiología , Factores de Riesgo , América del Sur/epidemiología , Polidactilia/epidemiología

RESUMEN

Radial longitudinal deficiency (RLD) is commonly associated with thumb hypoplasia. The association between RLD and radial polydactyly (RP) is uncommon, but case reports or case series have been reported. We report our experience of managing patients with this association. A total of 97 patients with RLD were seen in our department, of which six were children with concomitant RLD and RP. Four children had both RLD and RP in the same limb; of them, three also had RLD in the contralateral limb. The mean age at presentation was 11.6 months. Awareness of this association alerts the clinician to look for RLD in the presence of RP and vice versa. This case series supports recent experimental and clinical evidence that RP and RLD may be part of the same developmental spectrum. Further studies may guide its inclusion as a possible new category in the Oberg-Manske-Tonkin (OMT) classification of congenital upper-limb anomalies.Level of evidence: IV.

Asunto(s)

Polidactilia , Pulgar , Niño , Humanos , Lactante , Pulgar/anomalías

RESUMEN

Synpolydactyly (SPD) is caused by mutations in the transcription factor gene HOXD13. Such mutations include polyalanine expansion (PAE), but further study is required for the phenotypic spectrum characteristics of HOXD13 PAE. We investigated four unrelated Chinese families with significant limb malformations. Three PAEs were found in the HOXD13 polyalanine coding region: c.172_192dup (p.Ala58_Ala64dup) in Family 1, c.169_192dup (p.Ala57_Ala64dup) in Family 2, and c.183_210dup (p.Ala62_Ala70dup) in Family 3 and Family 4. Interestingly, we identified a new manifestation of preaxial polydactyly in both hands in a pediatric patient with an expansion of seven alanines, a phenotype not previously noted in SPD patients. Comparing with the wild-type cells and mutant cells with polyalanine contractions (PACs), the HOXD13 protein with a PAE of nine-alanine or more was difficult to enter the nucleus, and easy to form inclusion bodies in the cytoplasm, and with the increase of PAE, the more inclusion bodies were formed. This study not only expanded the phenotypic spectrum of SPD, but also enriched our understanding of its pathogenic mechanisms.

RESUMEN

PURPOSE: Resection of the underdeveloped digit and reconstruction of the robust digit is the standard treatment option for preaxial polydactyly of the hand. As an underdeveloped digit, the radial component is usually excised, whereas the ulnar component excision is rarely needed. This study aimed to evaluate the surgical results of ulnar component excision and radial component reconstruction in patients with preaxial polydactyly of the hand. METHODS: We retrospectively reviewed the medical records and radiographs of 809 patients (861 thumbs) who underwent surgery for preaxial polydactyly of the hand from November 2006 to June 2018. Among these, 22 (2.6%) thumbs in which the ulnar component was more hypoplastic or had more severe deformities than the radial component were treated with ulnar component excision and radial component reconstruction. The mean follow-up duration was 49 months (range, 12-142 months). We evaluated the Japanese Society for Surgery of the Hand scores and whether the patients were satisfied with the thumb function and appearance at the final follow-up. We also recorded any complications, such as reoperation. RESULTS: The mean Japanese Society for Surgery of the Hand score was 12.8 (range, 5-17). Six patients had poor results, 7 had fair results, and 2 had good results; however, none of the patients had an excellent result. Satisfaction with thumb function and appearance was reported in 11 (50%) and 6 (27%) cases, respectively. Thirteen of 22 (59.1%) cases involved reoperations, and the most common reason for reoperation was interphalangeal joint deviation of the remaining thumb. CONCLUSIONS: Ulnar component excision and radial component reconstruction are rare operative choices in preaxial polydactyly of the hand. Surgeons and patients should be aware that a considerable number of patients treated with this method required reoperations and had low clinical outcome scores. TYPE OF STUDY/ LEVEL OF EVIDENCE: Prognostic IV.

Asunto(s)

Procedimientos de Cirugía Plástica , Polidactilia , Humanos , Pulgar/anomalías , Estudios Retrospectivos , Polidactilia/cirugía

RESUMEN

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far.

Asunto(s)

Proteínas de la Membrana , Polidactilia , Humanos , Proteínas de la Membrana/genética , Linaje , Polidactilia/genética , Polidactilia/patología , Pulgar/patología

RESUMEN

Preaxial polydactyly (PPD) is a common congenital abnormality with an incidence of 0.8-1.4% in Asians, characterized by the presence of extra digit(s) on the preaxial side of the hand or foot. PPD is genetically classified into four subtypes, PPD type I-IV. Variants in six genes/loci [including GLI family zinc finger 3 (GLI3), ZPA regulatory sequence (ZRS), and pre-ZRS region] have been identified in PPD cases. Among these loci, ZRS is, perhaps, the most special and well known, but most articles only reported one or a few cases. There is a lack of reports on the ZRS-variant frequency in patients with PPD. In this study, we recruited 167 sporadic or familial cases (including 154 sporadic patients and 13 families) with PPD from Central-South China and identified four ZRS variants in four patients (2.40%, 4/167), including two novel variants (ZRS131A > T/chr7:g.156584439A > T and ZRS474C > G/chr7:g.156584096C > G) and two known variants (ZRS428T > A/chr7:g.156584142T > A and ZRS619C > T/chr7:g.156583951C > T). ZRS131A > T and ZRS428T > A were detected in PPD I cases and ZRS474C > G and ZRS619C > T combinedly acted to cause PPD II. The detectable rate of ZRS variants in PPD I was 1.60% (2/125), while PPD II was significantly higher (9.52%, 2/21). Three bilateral PPD cases harbored ZRS variants (13.64%, 3/22), suggesting that bilateral PPD was more possibly caused by genetic etiologies. This study identified two novel ZRS variants, further confirmed the association between ZRS and PPD I and reported a rare PPD II case resulted from the compound heterozygote of ZRS. This investigation preliminarily evaluated a ZRS variants rate in patients with PPD and described the general picture of PPD in Central-South China.

RESUMEN

BACKGROUND: Mirror foot or mirror image duplication of the foot is an extreme form and very rare congenital anomaly. There are limited management recommendations, and most cases are treated before walking age. We present the clinical findings, surgical treatment, and results of a rare case of mirror foot polydactyly. CASE PRESENTATION: A five-month-old girl with bilateral mirror foot was referred to our orthopaedic department. She was born full-term by the caesarian section and there was no family history of similar skeletal abnormalities and no history of drug or radiation exposure during gestation. The child had eight toes on the right foot and seven toes on the left with fully developed metatarsal, proximal, middle, and distal phalanges. Radiographs confirmed the diagnosis of mirror foot with a full complement of normal lateral toes and three additional complete rays medial to the right foot and two additional complete rays medial to the left foot. The patient underwent ray resection and concurrent reconstruction of the medial arch of the foot. A medial longitudinal incision was used to excised the right medial three rays and left medial two rays. The target of this surgical intervention was for aesthetic or cosmetic reasons and enabling the patient to allow shoe wear. CONCLUSION: Mirror-foot abnormalities are distinctly uncommon entities and represent extreme forms of congenital duplication of the preaxial polydactyly spectrum. Treatment on age of five-month-old with medial longitudinal incision had a satisfying clinical and radiological results.

RESUMEN

We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targeted gene panels when testing affected offspring born to consanguineous couples. In this way, exomic data from the parents are also made available for carrier screening, to identify heterozygous pathogenetic and likely pathogenetic variants in genes responsible for other recessive conditions, which may pose a risk for subsequent pregnancies.

Asunto(s)

Adenosina Trifosfatasas/genética , Cadherinas/genética , Lisencefalia/genética , Microcefalia/genética , Polidactilia/genética , Pulgar/anomalías , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Preescolar , Consanguinidad , Exoma/genética , Femenino , Mutación del Sistema de Lectura/genética , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Lactante , Recién Nacido , Lisencefalia/diagnóstico por imagen , Lisencefalia/patología , Microcefalia/diagnóstico por imagen , Microcefalia/patología , Linaje , Fenotipo , Polidactilia/diagnóstico por imagen , Polidactilia/patología , Hermanos , Pulgar/diagnóstico por imagen , Pulgar/patología , Secuenciación del Exoma

RESUMEN

OBJECTIVES: To describe a rare case of bilateral mirror feet with varus deformity and review of literature. METHODS: AP and oblique radiographs of both feet were taken. RESULTS: On radiographs, right foot showed eight toes and seven metatarsals while left foot showed eight toes and seven metatarsals, the three extra toes were present preaxially (on hallux side) in both feet, showing characteristics of postaxial toes termed as "mirror foot". Varus deformity was noted at the subtalar joint, otherwise tarsal bones appeared normal. No any syndromatic association was present. CONCLUSION: Mirror foot is a very rare congenital anomaly, we put forward this case for its rarity and unusual late presentation at the age of 22.

Asunto(s)

Deformidades Congénitas del Pie/diagnóstico , Metatarso Varo/diagnóstico , Polidactilia/diagnóstico , Femenino , Pie/diagnóstico por imagen , Deformidades Congénitas del Pie/complicaciones , Humanos , Metatarso Varo/complicaciones , Metatarso Varo/congénito , Polidactilia/complicaciones , Adulto Joven

RESUMEN

Background: Preaxial polydactyly (PPD) is one of the most common developmental malformations, with a prevalence of 0.8-1.4% in Asians. PPD is divided into four types, PPD I-IV, and PPD I is the most frequent type. Only six loci (GLI1, GLI3, STKLD1, ZRS, pre-ZRS, and a deletion located 240 kb from SHH) have been identified in non-syndromic PPD cases. However, pathogenesis of most PPD patients has never been investigated. This study aimed to understand the genetic mechanisms involved in the etiology of PPD I in a family with multiple affected members. Methods: We recruited a PPD I family (PPD001) and used stepwise genetic analysis to determine the genetic etiology. In addition, for functional validation of the identified GLIS1 variant, in vitro studies were conducted. GLIS1 variants were further screened in additional 155 PPD cases. Results: We identified a GLIS1 variant (NM_147193: c.1061G > A, p.R354H) in the PPD001 family. In vitro studies showed that this variant decreased the nuclear translocation of GLIS1 and resulted in increased cell viability and migration. RNA sequencing revealed abnormal TBX4 and SFRP2 expression in 293T cells transfected with mutant GLIS1. Additionally, we identified a GLIS1 variant (c.664G > A, p.D222N) in another PPD case. Conclusion: We identified two GLIS1 variants in PPD I patients and first linked GLIS1 with PPD I. Our findings contributed to future molecular and clinical diagnosis of PPD and deepened our knowledge of this disease.

RESUMEN

BACKGROUND: In preaxial polydactyly of the foot, the choice for excision of the lateral or medial hallux is not straightforward, in particular with proximal phalangeal (type IV) and metatarsal (type VI) duplication, because of anatomical characteristics. We evaluated whether medial or lateral hallux excision gives better outcomes in these duplication types, to help clinical decision making. METHODS: Children with type IV or type VI duplication (n=14, age: 4.4-17.2 years), who were operatively treated by excision of the lateral or medial hallux, were assessed for foot function using plantar pressure measurements and clinical examination. Foot aesthetics were scored by the child, an expert, and 10 laypersons, and additional patient-reported outcome questionnaires were obtained. Outcomes were compared between lateral and medial excision, per duplication type. RESULTS: In type IV duplication (n=11), lateral excision showed a better distribution of peak pressure between the hallux and first metatarsal with significantly lower median first metatarsal peak pressure (P = .008). Lateral excision showed more medial hallux deviation (P = .017). Foot aesthetics were not different between excision sides. In type VI duplication (n=12), lateral excision showed a 59% higher hallux peak pressure, larger medial hallux deviation (P = .004), and more reoperations. Foot aesthetics were scored significantly better after lateral excision by experts and laypersons. CONCLUSIONS: Foot function by virtue of plantar pressure was better after lateral hallux excision in type IV and after medial hallux excision in type VI duplication. Surgeons and laypersons perceived the foot as more normal after lateral excision in type VI, whereas children reported no differences. These outcomes can be used in clinical decision making. LEVEL OF EVIDENCE: Level III, therapeutic, comparative study.

Asunto(s)

Hallux/anomalías , Hallux/cirugía , Procedimientos de Cirugía Plástica/métodos , Polidactilia/cirugía , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Medición de Resultados Informados por el Paciente

RESUMEN

LACHT syndrome, or Mardini-Nyhan association, is an ultra-rare disorder, diagnosed solely by the clinical characteristics of lung agenesis, complex cardiac defects, and thumb anomalies. Only 12 patients have been reported worldwide, and here, we report a new clinical diagnosis of LACHT syndrome. Our patient was a male full-term newborn with left lung agenesis, congenital heart defects including ventricular septal defect, right-sided aortic arch, with aberrant left subclavian artery and Kommerell diverticulum, as well as left preaxial polydactyly and hemivertebra. Our patient appears to be the second LACHT syndrome case to also suffer from tracheal stenosis, which has only been reported once before in conjunction with this syndrome. In light of this, tracheal stenosis may be a phenotype for LACHT syndrome.

Asunto(s)

Anomalías Múltiples/diagnóstico , Anomalías Cardiovasculares/diagnóstico , Enfermedades Pulmonares/diagnóstico , Pulmón/anomalías , Polidactilia/genética , Arteria Subclavia/anomalías , Pulgar/anomalías , Estenosis Traqueal/diagnóstico , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/patología , Adulto , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/patología , Anomalías Cardiovasculares/diagnóstico por imagen , Anomalías Cardiovasculares/patología , Femenino , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/patología , Defectos del Tabique Interventricular/diagnóstico , Defectos del Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/patología , Humanos , Recién Nacido , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/patología , Masculino , Polidactilia/diagnóstico por imagen , Polidactilia/patología , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/patología , Tailandia/epidemiología , Pulgar/diagnóstico por imagen , Pulgar/patología , Estenosis Traqueal/diagnóstico por imagen , Estenosis Traqueal/patología

RESUMEN

INTRODUCTION: Reconstruction of Wassel IV-D radial polydactyly is challenging and requires a custom strategy dependent on the relative size and shape of the radial and ulnar duplicates. Herein, we describe a technique using a boot-shaped neurovascular island flap and review our outcomes. METHODS: Ninety-one consecutive patients had reconstruction with a boot-shaped neurovascular island flap. The flap was dissected out from the thumb to be removed. Specific flap modifications were inclusion of the lateral nail fold, Bruner incisions dorsally and volarly to reduce scarring at the interphalangeal (IP) joint and also complete mobilization of the island flap on its pedicle to allow easier inset. A flexor pollicis longus and extensor tendon rebalancing technique was used to correct the deviation of the reconstructed thumb IP joint. RESULTS: All boot-shaped neurovascular island flaps survived with good contour, shape, and symmetry. The average follow-up period was 25 months (range 6-60 months). Using the Japanese Society for Surgery of the Hand (JSSH) score for classification of outcomes, seven cases were classified as excellent and 84 cases as good. The median JSSH score was 18. The median Kapandji score for opposition was 9 (range 8-10). CONCLUSION: Using a boot-shaped neurovascular island flap completely mobilized on its pedicle with a custom strategy for each radial duplicate, good outcomes can be achieved in reconstruction of Wassel IV-D radial polydactyly. LEVEL OF EVIDENCE: Therapeutic Level IV.

Asunto(s)

Procedimientos de Cirugía Plástica/métodos , Polidactilia/cirugía , Colgajos Quirúrgicos , Pulgar/anomalías , Preescolar , Femenino , Humanos , Lactante , Masculino , Polidactilia/clasificación , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/inervación , Pulgar/cirugía

RESUMEN

BACKGROUND: Polydactyly is one of the most common congenital limb dysplasia in many animal species. Although preaxial polydactyly (PPD) has been comprehensively studied in humans as a common abnormality, the genetic variations in other animal species have not been fully understood. Herein, we focused on the pig, as an even-toed ungulate mammal model with its unique advantages in medical and genetic researches, two PPD families consisting of four affected and 20 normal individuals were sequenced. RESULTS: Our results showed that the PPD in the sampled pigs were not related to previously reported variants. A strong association was identified at ABCC4 and it encodes a transmembrane protein involved in ciliogenesis. We found that the affected and normal individuals were highly differentiated at ABCC4, and all the PPD individuals shared long haplotype stretches as compared with the unaffected individuals. A highly differentiated missense mutation (I85T) in ABCC4 was observed at a residue from a transmembrane domain highly conserved among a variety of organisms. CONCLUSIONS: This study reports ABCC4 as a new candidate gene and identifies a missense mutation for PPD in pigs. Our results illustrate a putative role of ciliogenesis process in PPD, coinciding with an earlier observation of ciliogenesis abnormality resulting in pseudo-thumb development in pandas. These results expand our knowledge on the genetic variations underlying PPD in animals.

Asunto(s)

Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Polidactilia/genética , Secuenciación Completa del Genoma/métodos , Animales , Femenino , Masculino , Mutación Missense/genética , Linaje , Porcinos

RESUMEN

PURPOSE: Thumb polydactyly and thumb hypoplasia are generally regarded as separate clinical entities. However, several case reports indicate that hypoplasia of both the thumb and the radius can occur in patients with thumb polydactyly and improved understanding of the genetics of the developing upper limb may give an embryologic explanation for this occurrence. Our hypothesis was that patients with preaxial polydactyly can have ipsilateral thumb hypoplasia that may not be recognized until after surgical reconstruction of the extra digit. METHODS: We searched our surgical database for all procedures performed on patients with a diagnosis of preaxial polydactyly between 2002 and 2014. We reviewed the medical record for demographic data, surgical procedures, and follow-up information. In addition, all available radiographs were reviewed. Through this, we identified patients with a diagnosis of ipsilateral thumb hypoplasia, including when in the course of treatment the diagnosis was made, and any related subsequent procedures. RESULTS: We reviewed 132 patients who underwent reconstruction of thumb polydactyly, 10 of whom were identified as having evidence of ipsilateral thumb hypoplasia, an incidence of 8.2%. The diagnosis of thumb hypoplasia was made before surgery in 3 of the 10 patients. One additional patient was noted to have a duplicate thumb on one side and a hypoplastic thumb on the contralateral side. CONCLUSIONS: This study supports the hypothesis that children with preaxial polydactyly can have ipsilateral thumb hypoplasia that may not be noted before surgery. In this study group, 8% of patients with preaxial polydactyly had ipsilateral hypoplasia. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Asunto(s)

Deformidades de la Mano , Polidactilia , Niño , Humanos , Polidactilia/diagnóstico por imagen , Polidactilia/cirugía , Radio (Anatomía) , Pulgar/anomalías , Pulgar/diagnóstico por imagen , Pulgar/cirugía

RESUMEN

Oral-facial-digital syndromes are a group of disorders with various subtypes. Type V, also known as the Thurston syndrome, is an autosomal recessive condition characterized by median cleft of the upper lip, postaxial polydactyly of hands and feet, and oral manifestations. Majority of the cases reported in the literature have been of Indian ethnic origin. We report a case of a possible variation of this syndrome in a 5-month-old Indian girl who presented with severe midline clefting, cleft palate, and atypically, preaxial polydactyly of the right hand.

Asunto(s)

Labio Leporino , Síndromes Orofaciodigitales , Polidactilia , Femenino , Dedos , Humanos , Lactante , Pulgar

RESUMEN

PURPOSE: Preaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown. METHODS: A rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model. RESULTS: A novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression. CONCLUSION: Our results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms.

Asunto(s)

Proteínas Hedgehog/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Esbozos de los Miembros/crecimiento & desarrollo , Proteínas de la Membrana/genética , Polidactilia/genética , Polimorfismo de Nucleótido Simple , Pulgar/anomalías , Regulación hacia Arriba , Animales , Células CACO-2 , Modelos Animales de Enfermedad , Femenino , Técnicas de Sustitución del Gen , Células HEK293 , Humanos , Intrones , Esbozos de los Miembros/metabolismo , Esbozos de los Miembros/patología , Masculino , Ratones , Ratones Transgénicos , Linaje , Polidactilia/metabolismo

RESUMEN

INTRODUCTION: While hallux valgus is a common deformity occurring in adults and adolescents, congenital hallux valgus is rare. There is a paucity of information available about the deformity and even less information about its cause. In fact, discrepancies exist within literature as to its etiology. This is a case report of bilateral congenital hallux valgus that appears to have been caused by preaxial polydactyly of the great toe, without a supernumerary digit, which to date has not been reported in literature. Markedly increased intermetatarsal and hallux valgus angles were present in both feet. Furthermore, bilateral interval improvement of the angulation occurred spontaneously without operative or non-operative intervention. This case reveals another potential cause of congenital hallux valgus not previously described. Our patient demonstrates that preaxial polydactyly could be another possible etiology of congenital hallux valgus. This case also demonstrates that magnetic resonance imaging (MRI) may be required for accurate diagnosis. CASE REPORT: The subject of this case report is a 6-month-old boy who presented with what appeared to be severe bilateral congenital hallux valgus. However, an MRI was suggestive of preaxial polydactyly without a supernumerary digit. At 26 months of age, clinical follow-up demonstrated that the deformity had improved and the patient was doing well clinically without intervention. CONCLUSION: Congenital hallux valgus is an uncommon deformity. Our patient demonstrates that the etiology may be incomplete preaxial polydactyly without a supernumerary digit. Overtime, even without treatment, the deformity appeared to improve, and the patient had no clinical complaints. The lack of an accessory ossicle or supernumerary digit makes our patient's case unique.