H Syndrome: Three New Cases from Morocco.

A 19-year-old girl presented with symmetric and bilateral hyperpigmentation, an indurated lesion that initially appeared on the axillary fold at the age of 14, which then extended to the lower back, anterior aspect of both thighs, and popliteal fold. No hypertrichosis was observed (Figure 1).The patient was the youngest of the four children, born from the first-degree consanguineous marriage. She was born at full term and weighed 2,420 g at birth. No similar patient was present in the family. The patient experienced delayed motor acquisition and stature growth (3rd percentile) until the age of 4. Right hypoacusis was diagnosed at the age of 6. She developed hallux valgus, flexion contracture of the fin-gers and toes, barrel deformity of the anterior thorax, and recurrent fever. The laboratory tests, including fasting blood glucose, -triglycerides, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were normal. Her abdominal, pelvic, and transthoracic ultrasound scans were normal, with no hepatosplenomegaly, lymphadenopathy, or cardiac abnormalities. Histologic analysis demonstrated patchy acanthosis of the epidermis, with orthokeratotic hyperkeratosis. Keratinocyte hyperpigmentation and spongiosis at certain areas were observed with moder-ate inflammation because of the infiltration of lymphocytes, histiocytes, and plasma cells. Immunohistochemical analysis showed macrosialin (CD68+) and common gamma chain (γc) CD132. Germline mutations in the SLC29A3 gene were not analyzed. The patient was prescribed dermocorticoids with depigmentation therapy, which demonstrated moderate clinical evolution.

A case of restrictive dermopathy in a Hutterite newborn: Diagnosis and creative skin-directed management.

Restrictive dermopathy is a lethal autosomal recessive disease characterized by tightly adherent skin, distinctive facial dysmorphisms, arthrogryposis, and pulmonary hypoplasia. While clinical findings are unique, histopathology and genetic analysis are critical for early diagnostic confirmation and to initiate appropriate management for this lethal disease. We report on a preterm Hutterite male neonate with biallelic ZMPSTE24 mutations to highlight the clinical and histopathological features of restrictive dermopathy and share our skin-directed management strategies.

Joint contractures is a recurrent clinical feature of individuals with neurodevelopmental disorder due to FOXP1 likely gene disruptive variants.

Haploinsufficiency of FOXP1 gene is responsible for a neurodevelopmental disorder presenting with intellectual disability (ID), autism spectrum disorder (ASD), hypotonia, mild dysmorphic features, and multiple congenital anomalies. Joint contractures are not listed as a major feature of FOXP1-related disorder. We report five unrelated individuals, each harboring likely gene disruptive de novo FOXP1 variants or whole gene microdeletion, who showed multiple joint contractures affecting at least two proximal and/or distal joints. Consistent with the phenotype of FOXP1-related disorder, all five patients showed developmental delay with moderate-to-severe speech delay, ID, ASD, and facial dysmorphic features. FOXP1 is implicated in neuronal differentiation and in organizing motor axon projections, thus providing a potential developmental basis for the joint contractures. The combination of joint contractures and neurodevelopmental disorders supports the clinical suspicion of FOXP1-related phenotype.

Congenital Flexor Contracture of Ulnar Digits Masquerading as Volkmann Ischemic Contracture.

ABSTRACT: Congenital flexion contracture of ulnar digits is a rare entity with few cases reported in medical literature. This condition is often misdiagnosed as Volkmann ischemic contracture as both have similar presentation. The patient history, physical examination, radiological investigation, and intra-operative findings can differentiate these 2 conditions clearly. A 14-year-old female presented to a tertiary care hospital with flexion deformity of the left long, ring, and little fingers without neurological deficit since she was 3 years old. Patient had decreased handspan with difficulty in grasping daily life objects. Finger flexion deformity was also not aesthetically acceptable due to social stigma. Patient finger contracture was managed with flexor pronator slide (Max-Page) operation. The muscle slide operation was done using concealed medial incision. Aesthetic and functional correction was achieved with no recurrence at subsequent follow-ups.

Combination of four features of SLC29A3 spectrum disorder in a child: A case report.

SLC29A3 spectrum disorder, also known as histiocytosis-lymphadenopathy plus syndrome (HLPS), presents a wide variety of multi-systemic manifestations that can be mistaken for other conditions. Herein, we report a 9-year-old girl who presented with a complex clinical presentation since birth, including chronic generalized lymphadenopathy in association with hepatosplenomegaly, short stature, flexion contractures, hearing loss, hyperpigmentation, and heart anomalies. She was ultimately diagnosed with the SLC29A3 spectrum disorder.

[Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report].

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 |IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

The Delphi of ORACLE: An Expert Consensus Survey for the Development of the Observational Risk Assessment of Contractures (Longitudinal Evaluation).

OBJECTIVE: Despite rising prevalence rates, no standard tool is available to identify individuals at risk of developing contractures. This study aimed to gain expert consensus on items for the development of the Observational Risk Assessment Tool for Contractures: Longitudinal Evaluation (ORACLE) for care home residents. DESIGN: A two-round, online modified Delphi study. PARTICIPANTS: Panellists were qualified healthcare professionals with a background in physiotherapy, occupational therapy, nursing, and rehabilitation medicine. MAIN OUTCOME MEASURES: In the first round, the experts were asked to rate the predesigned list of items on a Likert scale while in the second round, consensus was sought in the areas of disagreement identified in the previous round. RESULTS: The two rounds of the Delphi survey included 30 and 25 panellists, respectively. The average clinical and academic experience of the panellists was 22.2 years and 10.5 years, respectively. The panel demonstrated a high level of consensus regarding the clinical factors (10 out of 15 items); preventive care approaches (9 out of 10 items), and contextual factors (12 out of 13 items) ranging from 70% to 100%. CONCLUSION: This Delphi study determined expert consensus on items to be included in a contracture risk assessment tool (ORACLE). The items were related to factors associated with joint contractures, appropriate preventive care interventions, and potentially relevant contextual factors associated with care home settings. The promise of a risk assessment tool that includes these items has the capacity to reduce the risk of contracture development or progression and to trigger timely and appropriate referrals to help prevent further loss of function and independence.

Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures.

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes.

Expanding the phenotypic spectrum for CDK8-related disease: A case report.

BACKGROUND: Cyclin-dependent kinase 8 (CDK8) is part of a regulatory kinase module that regulates the activity of the Mediator complex. The Mediator, a large conformationally flexible protein complex, goes on to regulate RNA polymerase II activity, consequently affecting transcriptional regulation. Thus, inactivating mutations of the genes within the kinase module cause aberrant transcriptional regulation and disease, namely, CDK8-related intellectual developmental disorder with hypotonia and behavioral abnormalities (IDDHBA). CASE PRESENTATION: We describe, for the first time, a likely pathogenic heterozygous CDK8 variant c.599G>A, p.(Arg200Gln) inherited from the biological mother. The clinical presentation of the child and mother is within the described clinical spectrum for IDDHBA; however, undocumented progressive contractures of the hips and knees as well as scoliosis were also observed in the child. This phenotype was not found in the mother, highlighting a heterogenous presentation for the same variant within the same family. Furthermore, the described clinical presentation may further support the notion of a module- or Mediator-related syndrome with varying clinical presentation. CONCLUSION: This case report documents the first inherited case of IDDHBA and expands the phenotypic spectrum for CDK8-related disease to include undocumented progressive contractures of the hips and knees as well as scoliosis, which may support the notion of a module- or Mediator-related syndrome with varying clinical presentation.

The examination and treatment of soft tissue contracture of the elbow.

Treatment of the stiff elbow can be a challenging task. A thorough understanding of normal elbow anatomy and the potential causes of elbow contracture are essential for the development of effective treatment strategies. This chapter provides a review of key points for the treating surgeon including normal elbow anatomy, etiological factors that commonly contribute to elbow stiffness, physical examination and imaging of the stiff elbow, and treatment options for contracture correction.

Toward a Consensus Aproach for Assessing Capsular Contracture Severity and Progression: A Systematic Review.

BACKGROUND: Breast implants are the most commonly used medical devices in plastic surgery, and capsular contracture (CC) is one of the most common complications. However, our assessment of CC is based largely on Baker grade, which is problematically subjective and affords only four possible values. METHODS: The authors performed a systematic review concluding in September of 2021 in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. It identified 19 articles that propose approaches to measuring CC. RESULTS: In addition to Baker grade, the authors identified several modalities reported to measure CC. These included magnetic resonance imaging, ultrasonography, sonoelastography, mammacompliance measuring devices, applanation tonometry, histologic evaluation, and serology. Capsule thickness and other measures of CC inconsistently correlated with Baker grade, whereas the presence of synovial metaplasia was consistently associated with Baker grade I and II, but not III and IV capsules. CONCLUSIONS: There remains no particular method to reliably and specifically measure the contracture of capsules that form around breast implants. As such, we would recommend that research investigators use more than one modality to measure CC. Other variables that can impact breast implant stiffness and associated discomfort beyond CC need to be considered when evaluating patient outcomes. Given the value placed on CC outcomes in assessing breast implant safety, and the prevalence of breast implants overall, the need for a more reliable approach to measuring this outcome persists.

Classification of elbow stiffness.

Stiffness is a clinical disorder that affects the patient's function of the entire upper limb. Many classifications systems have been developed for elbow stiffness based on the plane of motion, severity, aetiology, prognosis or anatomical location. A new classification, the Stiffness types and Influencing Factors Classification System, is proposed as a treatment algorithm to guide the surgical treatment and the preferred operative approach (open or arthroscopic).

Early Elbow Flexion Contracture Predicts Shoulder Contracture in Infants with Brachial Plexus Birth Injury.

OBJECTIVE: To determine if children who present with an elbow flexion contracture (EFC) from brachial plexus birth injury (BPBI) are more likely to develop shoulder contracture and undergo surgical treatment. STUDY DESIGN: Retrospective review of children <2 years of age with BPBI who presented to a single children's hospital from 1993 to 2020. Age, elbow and shoulder range of motion (ROM), imaging measurements, and surgical treatment and outcome were analyzed. Patients with an EFC of ≥10° were included in the study sample. Data from 2445 clinical evaluations (1190 patients) were assessed. The final study cohort included 72 EFC cases matched with 230 non-EFC controls. Three patients lacked sufficient follow-up data. RESULTS: There were 299 included patients who showed no differences between study and control groups with respect to age, sex, race, ethnicity, or functional score. Patients with EFC had 12° less shoulder range of motion (95% CI, 5°-20°; P < .001) and had 2.5 times the odds of shoulder contracture (OR, 2.5; 95% CI, 1.3-4.7; P = .006). For each additional 5° of EFC, the odds of shoulder contracture increased by 50% (OR, 1.5; 95% CI, 1.2-1.8; P < .001) and odds of shoulder procedure increased by 62% (OR, 1.62; 95% CI, 1.04-2.53; P = .03). Sensitivity of EFC for predicting shoulder contracture was 49% and specificity was 82%. CONCLUSIONS: In patients with BPBI <2 years of age, presence of EFC can be used as a screening tool in identifying shoulder contractures that may otherwise be difficult to assess. Prompt referral should be arranged for evaluation at a BPBI specialty clinic, because delayed presentation risks worsening shoulder contracture and potentially more complicated surgery.

[Surgical treatment of combined injuries of the neck and shoulder joints]. / Khirurgicheskoe lechenie sochetannykh porazhenii shei i plechevykh sustavov.

OBJECTIVE: To develop the algorithm for effective surgical restoration of shoulder joint and neck functions and acceleration of social and labor rehabilitation. MATERIAL AND METHODS: There were 116 patients with combined consequences of burns of the neck and shoulder joints between 2012 and 2021. These ones amounted to 29.4% of all patients with lesions of the neck or shoulder joints. Simultaneous surgeries with correction of post-burn cicatricial deformities and contractures were performed in 66 patients (56.9%). Age of patients ranged from 18 to 72 years, and 96% of them were employable. There were 89 (76.7%) women and 27 (23.3%) men. We assessed spread and localization of cicatricial process, as well as restriction of mobility of the neck and shoulder joint to select optimal surgical approach. Classification of neck deformities and contractures of shoulder joints considering severity of cicatricial lesion and functional impairment made it possible to systematize the approach to reconstructive procedures. Reconstructive surgery included repair with local tissues including skin-fatty flap, non-perforated split or full-thickness skin autograft, rotated flaps including those based on perforator vessels, as well as preliminary skin stretching. RESULTS: In general, 116 patients with combined lesions of the neck and shoulder joints underwent 314 surgeries. To accelerate rehabilitation, we performed simultaneous surgeries with correction of deformities and contractures in 66 patients (56.9%). Staged reconstructive surgeries were carried out in 50 patients. Acute dermotension and skin-fatty neck flap grafting were the most common for deformities and contractures of the neck. Skin-fatty axillary flap was used in most patients with contractures of shoulder joints. CONCLUSION: Simultaneous surgeries can accelerate rehabilitation. Correct algorithm of staged surgical treatment reduces rehabilitation period and eliminates functional disorders.

[Diagnosis and treatment of finger flexion contracture caused by forearm flexor disease].

Objective: To summarize the clinical characteristics, differential diagnosis, and treatment methods of finger flexion contracture caused by three kinds of forearm flexor diseases. Methods: Between December 2008 and August 2021, 17 patients with finger flexion contracture were treated, including 8 males and 9 females, aged 5-42 years, with a median of 16 years. The disease duration ranged from 1.5 months to 30 years, with a median of 13 years. The etiology included 6 cases of Volkmann's contracture, all of which were flexion deformity of the 2nd to 5th fingers, accompanied by limitation of thumb dorsiflexion in 3 cases and limitation of wrist dorsiflexion in 3 cases; 3 cases of pseudo-Volkmann's contracture, including 2 cases of flexion deformity of middle, ring, and little fingers, and 1 case of flexion deformity of ring and little fingers; 8 cases of ulnar finger flexion contracture caused by forearm flexor disease or anatomical variations, all of which were flexion deformity of middle, ring, and little fingers. Operations such as slide of flexor and pronator teres origin, excision of abnormal fibrous cord and bony prominence, and release of entrapped muscle (tendon) were performed. Hand function was evaluated according to WANG Haihua's hand function rating standard or modified Buck-Gramcko classification standard, and muscle strength was evaluated according to British Medical Research Council (MRC) muscle strength rating standard. Results: All patients were followed up 1-10 years (median, 1.5 years). At last follow-up, 8 patients with contracture caused by forearm flexor disease or anatomical variations and 3 patients with pseudo-Volkmann's contracture achieved excellent hand function, with muscle strength of grade M5 in 6 cases and grade M4 in 5 cases. One patient with mild Volkmann's contracture and 3 patients with moderate Volkmann's contracture without severe nerve damage had excellent hand function in 2 cases and good in 2 cases, with muscle strength of grade M5 in 1 case and grade M4 in 3 cases. Two patients with moderate or severe Volkmann's contracture had poor hand function, with 1 case of muscle strength of grade M3 and 1 case of grade M2, which improved when compared with those before operation. The overall excellent and good rate of hand function and the proportion of patients with muscle strength of grade M4 and above were 88.2% (15/17), respectively. Conclusion: The finger flexion contracture caused by different etiology can be differentiated by analyzing the history, physical examination, radiographs, and intraoperative findings. After different surgical treatments, such as resection of contracture band, release of compressed muscle (tendon), and downward movement of flexor origin, most patients have a good outcome.

Predictive factors of the contracture test for diagnosing malignant hyperthermia in a Brazilian population sample: a retrospective observational study

Abstract Introduction Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. Objective To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. Methods We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). Results Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). Conclusions Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Predictive factors of the contracture test for diagnosing malignant hyperthermia in a Brazilian population sample: a retrospective observational study.

INTRODUCTION: Malignant Hyperthermia (MH) is a pharmacogenetic, hereditary and autosomal dominant syndrome triggered by halogenates/succinylcholine. The In Vitro Contracture Test (IVCT) is the gold standard diagnostic test for MH, and it evaluates abnormal skeletal muscle reactions of susceptible individuals (earlier/greater contracture) when exposed to caffeine/halothane. MH susceptibility episodes and IVCT seem to be related to individual features. OBJECTIVE: To assess variables that correlate with IVCT in Brazilian patients referred for MH investigation due to a history of personal/family MH. METHODS: We examined IVCTs of 80 patients investigated for MH between 2004‒2019. We recorded clinical data (age, sex, presence of muscle weakness or myopathy with muscle biopsy showing cores, genetic evaluation, IVCT result) and IVCT features (initial and final maximum contraction, caffeine/halothane concentration triggering contracture of 0.2g, contracture at caffeine concentration of 2 and 32 mmoL and at 2% halothane, and contraction after 100 Hz stimulation). RESULTS: Mean age of the sample was 35±13.3 years, and most of the subjects were female (n=43 or 54%) and MH susceptible (60%). Of the 20 subjects undergoing genetic investigation, 65% showed variants in RYR1/CACNA1S genes. We found no difference between the positive and negative IVCT groups regarding age, sex, number of probands, presence of muscle weakness or myopathy with muscle biopsy showing cores. Regression analysis revealed that the best predictors of positive IVCT were male sex (+12%), absence of muscle weakness (+20%), and personal MH background (+17%). CONCLUSIONS: Positive IVCT results have been correlated to male probands, in accordance with early publications. Furthermore, normal muscle strength has been confirmed as a significant predictor of positive IVCT while investigating suspected MH cases.

Renal Involvement in H Syndrome, A Rare Cause of Diabetes Mellitus: Case Report.

BACKGROUND: H syndrome is a rare genodermatosis deriving from a mutation in the SLC29A3 gene and affecting numerous systems, particularly the skin. The syndrome exhibits different clinical characteristics involving several systems, most beginning with the letter "H." The most common clinical findings are cutaneous hyperpigmentation, flexion contracture in the fingers, hearing loss, short stature, insulin-dependent diabetes mellitus, heart anomalies, hepatosplenomegaly, and hypogonadism. Fewer than 150 cases have been reported so far and vast majority of them consisted with patients with Arab ethnicity. CASE PRESENTATION: We describe a patient presenting with short stature, developing diabetes mellitus at follow-ups, with homozygous deletion determined in exon 3 of the SLC29A3 gene, and diagnosed with H syndrome, reported due to the presence and rarity of renal involvement (hematuria and proteinuria). CONCLUSION: In conclusion, despite its rarity, endocrinologists, rheumatologists/nephrologists, and dermatologists need to be aware of H syndrome as a pleiotropic syndrome. H syndrome should be considered in the differential diagnosis of patients with cutaneous hyperpigmentation (particularly in the bilateral thigh and calf region) together with proteinuria/hematuria. In addition, periodic urine analysis should be performed in patients with H syndrome.