Coexistence of dyschondrosteosis associated to SHOX deficiency, pseudohypoparathyroidism 1B, and chronic autoimmune thyroiditis: a case report.

We present an unusual case of SHOX deficiency associated with Léri-Weill dyschondrosteosis (LWD), Hashimoto's thyroiditis and pseudohypoparathyroidism 1B in a young woman. To our knowledge, this is the first ever report of these disorders coexisting. At the age of nine years, the proband was diagnosed of hypothyroidism due to Hashimoto's thyroiditis, and developed biochemical abnormalities consistent with hyperphosphatemia, mild hypocalcemia and elevated parathyroid hormone without any clinical symptoms except short stature. Replacement therapy with levothyroxine, calcium and alphacalcidol was initiated. The diagnosis of pseudohypoparathyroidism 1B was confirmed at the age of 17.5 years with the demonstration of methylation alteration at the GNAS locus. At the age of 16 years, 3.5 years after her menarche, she presented clear features of LWD. A large deletion of the SHOX gene was confirmed. Family genetic tests were not doable since she was adopted. We discuss the diagnostic challenges of these coexisting rare endocrinopathies.

Defining Features of Hand Anomalies in Severe Thumb Hypoplasia: A Classification Modification.

PURPOSE: To investigate morphologic hand anomalies in children with severe but unclassifiable forms of thumb hypoplasia and radial-sided hand deficiency. METHODS: We identified 15 extremities in 13 patients with severe thumb hypoplasia and associated absent radial-sided digits through the Congenital Upper Limb Differences registry. All patients had forearm involvement. Medical records, clinical photographs, and radiographs were evaluated. Radial longitudinal deficiency (RLD) and thumb hypoplasia were classified according to the Bayne and Klug classification and modified Blauth classification, respectively. Unusual or defining associated hand characteristics were identified and categorized. RESULTS: The most common type of forearm abnormality was absence of the radius (Bayne and Klug type IV), which was present in 10 extremities in the cohort. All 15 extremities had absent thumbs with loss of additional digits. In 6 patients, RLD was part of a syndrome (46%). CONCLUSIONS: Severe forms of thumb hypoplasia in RLD are uncommon. We propose a further modification of the Blauth classification of thumb hypoplasia, type VI, for improved communication regarding this severe type of radial deficiency involving the hand. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Revisiting the management of Manske Type 3B and 4 thumb hypoplasia.

The traditional management of Manske 3B and 4 thumbs is index finger pollicization. Recently, the transfer of composite tissues from the foot to reconstruct the thumb or the carpometacarpal joint has allowed the preservation of a five-digit hand. Concerns remained about the donor site and also the limited functional and cosmetic outcomes that could be achieved. This article challenges the existing dogma in the management of hypoplastic thumbs, that pollicization should always be the reference standard. We describe the evolution of techniques with free vascularized metatarsal transfer, our refinements and our proposal for a new classification system that accommodates these modifications. With increased experience, acceptable outcomes that are comparable with pollicization can be achieved.

Long-term outcomes after pollicization: a mean 11-year follow-up study.

This study evaluates the long-term results of pollicization for a congenitally absent or severely hypoplastic thumb. Twenty-nine patients with 34 pollicizations were divided to two groups: those with simple thumb hypoplasia (22 pollicizations) and those with radial longitudinal dysplasia (12 pollicizations). The patients were followed from 1.3 to 32 years, with a mean follow-up time of 11 years. The patients were examined clinically and radiologically, and they completed a questionnaire concerning satisfaction with appearance, function, and social interaction. The Percival score was also calculated. In both groups, grip and pinch strengths of the operated hands were inferior to the normative age-related values. Radiologically, flattening of the original metacarpal head was found in 20 out of the 34 operated hands. We found better patient satisfaction in the simple hypoplasia group than in the radial longitudinal dysplasia group. The functional outcomes and patients' satisfaction did not correlate with the age of patients at operation. Level of evidence: IV.

Post-traumatic wind swept deformity: five volar carpometacarpal dislocations.

Carpometacarpal (CMC) joint dislocation other than thumb are rare injuries and can be easily missed. These injuries account for <1% of all hand injuries and are frequently overlooked or missed. CMC dislocations can occur either in dorsal or volar direction and be associated with fractures. However, dorsal dislocation is more commonly encountered than volar dislocation. Volar CMC joint dislocations are rare and need a high level of suspicion for diagnosing and prevention of complications. We present a 36-year-old woman with post-traumatic neglected volar dislocation of all the five CMC joints leading to a windswept deformity of the hand.

Adducted thumb as an isolated morphologic finding: an early sonographic sign of impaired neurodevelopment: A STROBE compliant study.

Fetal adducted thumbs have been described in association with hydrocephalus and other abnormalities, but in cases without other structural malformations the determination of prognosis and recurrence risk is challenging. The aim of our study is to analyze the characteristics, natural history, and postnatal outcome of such cases.A retrospective study was conducted over a period of 4 years in a tertiary referral center. All fetuses diagnosed as adducted thumbs without other structural malformations comprised the study group. Prenatal sonographic features and neonatal outcome are documented.There were 4 cases of fetal adducted thumbs diagnosed during the study period. No cases demonstrated other structural malformations throughout the gestation. A smaller head was noted in 2 cases during the follow-up, and all cases presented with polyhydramnios on the first or ensuing scans. Three cases died after birth due to swallowing or breathing difficulty, and the surviving 1 showed convulsion and mental retardation.Fetal adducted thumb might be an early and specific sonographic marker of impaired neurodevelopment. Close follow-up and genetic investigation should be performed in these cases. Ultrasound examination plays an important role in the prenatal diagnosis and counseling of cases without detailed prenatal genetic analysis.

Prenatal diagnosis of fetal adducted thumbs.

PURPOSE: One of the greatest challenges with the finding of adducted thumbs in the prenatal setting is the determination of whether this finding is associated with an underlying genetic syndrome. The aim of the present study is to describe the characteristics and outcome of prenatal sonographic diagnosis of adducted thumbs. METHODS: A retrospective study was conducted over a period of 17 years in a tertiary referral center. All fetuses diagnosed prenatally with adducted thumbs comprised the study group. Prenatal sonographic assessment and neonatal outcome are presented. RESULTS: Six fetuses were evaluated for adducted thumbs over the 17-year period. In three cases, the parents elected termination of pregnancy for severe associated anomalies. In one case partial resolution was observed during the third trimester. Of the remaining two fetuses, one had a single umbilical artery and in the second the adducted thumbs were an isolated finding. Post-natal evaluation in both cases revealed bilateral adducted thumbs. Apart from orthopedic follow up no further interventions were needed. CONCLUSIONS: Prenatal diagnosis of adducted thumbs should be followed by a meticulous fetal ultrasound examination combined with genetic counseling. According to our cohort, if associated anomalies are excluded, isolated cases seem to have a favorable diagnosis.

Single forearm radius and ulna asymmetric lengthening in multiple cartilaginous exostoses: a case report and a long-term follow-up.

We describe one case of forearm deformity in a patient affected by multiple cartilaginous exostoses - also known as the forearm 'candy stick deformity'. Surgical treatment usually focuses on the correction of the wrist deformity without correcting the forearm shortening, the latter not being given the same consideration as lower limb shortening. In the presented case, radius and ulna corticotomies were performed and distal forearm deformity and shortening were corrected by two independent monoaxial external fixators, with full pronosupination. It is our belief that simultaneous treatment of forearm shortening and deformity not only results in an improved clinical and functional result but also provides significant psychological benefit. We recommend a long-term follow-up.

A very rare cause of acro-osteolysis: Hajdu-Cheney syndrome.

Acro-osteolysis is not uncommon and occurs in several conditions. Additional clinical and paraclinical findings and sometimes the performance of molecular tests can help to clarify the diagnosis. Here, we report the case of a 36-year-old woman who was referred to our department because of acute pain in the extremity of the left index finger. However, subsequent clinical examination also revealed short digits with pseudo-clubbing related to acro-osteolysis. Furthermore, severe osteoporosis, a moderate dysmorphic face, joint hypermobility, biological variables within normal ranges and her clinical history led us to consider the diagnosis of Hajdu-Cheney syndrome. Molecular analysis confirmed the diagnosis with the identification of a mutation in the NOTCH2 gene. The patient received bisphosphonate therapy, which resulted in some clinical and biological improvement 12 months later.

Pitfalls in wrist and hand ultrasound.

OBJECTIVE: The purpose of this article is to review a number of diagnostic pitfalls related to ultrasound evaluation of the hand and wrist. Such pitfalls relate to evaluation of ten-dons (extensor retinaculum, multiple tendon fascicles, tendon subluxation), inflammatory arthritis (incomplete evaluation, misinterpretation of erosions, failure to evaluate for enthesitis), carpal tunnel syndrome (inaccurate measurements, postoperative assessment), ulnar collateral ligament of the thumb (misinterpretation of the adductor aponeurosis and displaced tear), wrist ganglion cysts (incomplete evaluation and misdiagnosis), and muscle variants. CONCLUSION: Although ultrasound has been shown to be an effective imaging method for assessment of many pathologic conditions of the wrist, knowledge of potential pitfalls is essential to avoid misdiagnosis and achieve high diagnostic accuracy.

New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene.

BACKGROUND: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have been reported. A deregulated expression of TRPS1 has been hypothesised as cause of the TRPS phenotype of these patients. CASE PRESENTATION: We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting TRPS1 or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of TRPS1, and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA LINC00536, at approximately 300 kb from the TRPS1 5' end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325 kb from the TRPS1 promoter. CONCLUSIONS: We suggest that the disruption of the genomic architecture of cis regulatory elements downstream the TRPS1 5' region, combined with the translocation of a novel enhancer element nearby TRPS1, might be the pathogenetic mechanism underpinning the proband's phenotype. The clinical and genetic characterisation of the present subject allowed us to make a genetic diagnosis in the context of a known syndrome, contributing to a better comprehension of the complex transcriptional regulation of TRPS1 and TRPS ethiopathogenesis.

Melorheostosis of the hand affecting the c6 sclerotome and presenting with carpal tunnel syndrome.

Melorheostosis is a rare, progressive bone disease accompanied by hyperostosis and soft tissue fibrosis. While affected adults present with contracture and pain, children present with limb length discrepancy and deformity. We report the case of a 20-year-old woman with melorheostosis since childhood who presented with right hand deformity and numbness. Radiographs showed not only a combination of dense sclerosis and opacities, but also the classic 'flowing candle wax' appearance. Radiography can be used to identify melorheostosis, thus preventing unnecessary bone biopsies. Carpal tunnel release revealed the presence of a thickened flexor retinaculum and a degenerated median nerve distal to the retinaculum, but did not show hyperostosis. This case highlights the role of nerve decompression in melorheostosis and the importance of early identification of the disease to prevent unnecessary bone biopsies.