A novel pathogenic variant in MYO18B associating early-onset muscular hypotonia, and characteristic dysmorphic features, delineation of the phenotypic spectrum of MYO18B-related conditions.

Homozygous loss-of-function variants in MYO18B have been associated with congenital myopathy, facial dysmorphism and Klippel-Feil anomaly. So far, only four patients have been reported. Comprehensive description of new cases that help to highlight recurrent features and to further delineate the phenotypic spectrum are still missing. We present the fifth case of MYO18B-associated disease in a newborn male patient. Trio exome sequencing identified the previously unreported homozygous nonsense variant c.6433C>T, p.(Arg2145*) in MYO18B (NM_032608.5). While most phenotypic features of our patient align with previously reported cases, we describe the prenatal features for the first time. Taking the phenotypic description of our patient into account, we propose that the core phenotype comprises a severe congenital myopathy with feeding difficulties in infancy and characteristic dysmorphic features.

Demographics, presentation and symptoms of patients with Klippel-Feil syndrome: analysis of a global patient-reported registry.

INTRODUCTION: Klippel-Feil syndrome (KFS) occurs due to failure of vertebral segmentation during development. Minimal research has been done to understand the prevalence of associated symptoms. Here, we report one of the largest collections of KFS patient data. METHODS: Data were obtained from the CoRDS registry. Participants with cervical fusions were categorized into Type I, II, or III based on the Samartzis criteria. Symptoms and comorbidities were assessed against type and location of fusion. RESULTS: Seventy-five patients (60F/14M/1 unknown) were identified and classified as: Type I, n = 21(28%); Type II, n = 15(20%); Type III, n = 39(52%). Cervical fusion by level were: OC-C1, n = 17(22.7%), C1-C2, n = 24(32%); C2-C3, n = 42(56%); C3-C4, n = 30(40%); C4-C5, n = 42(56%); C5-C6, n = 32(42.7%); C6-C7, n = 25(33.3%); C7-T1, n = 13(17.3%). 94.6% of patients reported current symptoms and the average age when symptoms began and worsened were 17.5 (± 13.4) and 27.6 (± 15.3), respectively. Patients reported to have a high number of comorbidities including spinal, neurological and others, a high frequency of general symptoms (e.g., fatigue, dizziness) and chronic symptoms (limited range of neck motion [LROM], neck/spine muscles soreness). Sprengel deformity was reported in 26.7%. Most patients reported having received medication and invasive/non-invasive procedures. Multilevel fusions (Samartzis II/III) were significantly associated with dizziness (p = 0.040), the presence of LROM (p = 0.022), and Sprengel deformity (p = 0.036). CONCLUSION: KFS is associated with a number of musculoskeletal and neurological symptoms. Fusions are more prevalent toward the center of the cervical region, and less common at the occipital/thoracic junction. Associated comorbidities including Sprengel deformity may be more common in KFS patients with multilevel cervical fusions. These slides can be retrieved under Electronic Supplementary Material.

Type III Klippel-Feil syndrome: case report and review of associated craniofacial anomalies.

Klippel-Feil syndrome (KFS) is a complex syndrome of osseous and visceral anomalies that include the classical clinical triad of short neck, limitation of head and neck movements and low posterior hairline. It may also be associated with anomalies of the genitourinary, musculoskeletal, neurologic and cardiac systems. We report a case of type III KFS with associated rib anomalies such as cervical rib, fusion and bifid ribs, scoliosis and fused crossed renal ectopia. The aim of this paper was to summarize all craniofacial anomalies that occur in association with KFS, so that clinicians would be aware of them during diagnosis and treatment planning.

Massive diminution of the cervical spine: one case report.

The authors report a 13-year-old female with shunted hydrocephalus who when evaluated for neck pain, was found to have not only fusion of cervical vertebrae but significant diminution of the cervical spine. Following our review of the classification of KFA and our case report, the current interpretation of Klippel and Feil's original description of KFA should be re-evaluated, and/or a new class of KFA used, that of complete or partial cervical vertebrae agenesis and associated abnormalities, should be considered in the classification of this anomaly.

Classification of congenitally fused cervical patterns in Klippel-Feil patients: epidemiology and role in the development of cervical spine-related symptoms.

STUDY DESIGN: A retrospective cohort and series review. OBJECTIVES: To determine the role of cervical spine fusion patterns on the development of cervical spine-related symptoms (CSS) in patients with Klippel-Feil syndrome (KFS) and evaluate age- and time-dependent factors that may contribute to fused cervical patterns and the development of the CSS. SUMMARY OF BACKGROUND DATA: Although the "hallmark" of KFS is the presence of congenitally fused cervical vertebrae, the epidemiology and role of specific cervical fused patterns are limited. In addition, the incidence of symptoms and various age- and time-dependent factors that are directly attributed to the congenitally fused cervical segments in KFS patients is unknown. METHODS: A radiographic and clinical review of 28 KFS patients at a single institution. Radiographically, Type I patients were defined as having a single congenitally fused cervical segment. Type II patients demonstrated multiple noncontiguous, congenitally fused segments, and Type III patients had multiple contiguous, congenitally fused cervical segments. Clinical records were reviewed for patient demographics, presence and type of symptoms, and clinical course. RESULTS: Twelve males and 16 females were reviewed for clinical follow-up (mean, 8.5 years) and radiographic assessment (mean, 8.0 years). The mean age at presentation was 7.1 years; mean age of onset of CSS was 11.9 years. Clinically, 64% had no complaints referable to their cervical spine. Radiographically, 25%, 50%, and 25% were Type I, Type II, and Type III, respectively. At final clinical follow-up, 2 patients were myelopathic (Type II and Type III) and 2 were radiculopathic (Type II and Type III). Type III patients were largely asymptomatic but were associated with the highest risk in developing radiculopathy or myelopathy than Type I or Type II patients. Axial symptoms were predominantly associated with Type I patients. Myelopathic patients developed initial CSS earlier (meanage, 10.6 years) than patients with predominant axial (mean age, 13.0 years) or radiculopathic symptoms (mean age, 18.6 years) (P > 0.05). Patients with radiculopathy or myelopathy were diagnosed at a mean age of 17.9 years. Type I patients were predominantly females, while males were largely Type III. Surgery entailed 11% of patients, composed of 2 myelopathic patients (Type II and Type III) and 1 radiculopathic patient (Type II). CONCLUSIONS: In our review, 36% of KFS patients had CSS and the majority had axial symptoms. Axial neck symptoms were highly associated with Type I patients, whereas predominant radicular and myelopathic symptoms occurred in Type II and Type III patients. This classification system has promise for early detection for CSS. Activity modification should be stressed in KFS patients at high risk for neurologic compromise.

Deformidad de Klippel-Feil con anomalía de Arnold-Chiari tipo I y siringomielia / Klippel-Feil deformity with Arnold -Chiari type I malformation and syringomyelia

La deformidad de Klippel-Feil es una anomalía del desarrollo que afecta comúnmente a las vértebras cervicales. La entidad se asocia por lo general con otras deformidades con anomalías o sin ellas tanto del sistema nervioso como de otros sistemas de órganos. Se reporta un paciente adulto de 35 años de edad que sin antecedentes familiares o personales de enfermedades causantes de deformidades con anomalías óseas o sin ella se le diagnóstica la enfermedad de Klippel-Feil, con anomalías neurales en la resonancia magnética nuclear. Clínicamente presentaba síntomas y signos propios de la compresión medulocerebeloso por lo que se le realiza una craniectomía de fosa posterior con laminectomía de C1 y duroplastia. La evolución es satisfactoria con la desaparición de la mayoría de los síntomas

Deformidad de Klippel-Feil con anomalía de Arnold-Chiari tipo I y siringomielia / Klippel-Feil deformity with Arnold -Chiari type I malformation and syringomyelia

La deformidad de Klippel-Feil es una anomalía del desarrollo que afecta comúnmente a las vértebras cervicales. La entidad se asocia por lo general con otras deformidades con anomalías o sin ellas tanto del sistema nervioso como de otros sistemas de órganos. Se reporta un paciente adulto de 35 años de edad que sin antecedentes familiares o personales de enfermedades causantes de deformidades con anomalías óseas o sin ella se le diagnóstica la enfermedad de Klippel-Feil, con anomalías neurales en la resonancia magnética nuclear. Clínicamente presentaba síntomas y signos propios de la compresión medulocerebeloso por lo que se le realiza una craniectomía de fosa posterior con laminectomía de C1 y duroplastia. La evolución es satisfactoria con la desaparición de la mayoría de los síntomas(AU)

Heterogeneity in Klippel-Feil syndrome: a new classification.

BACKGROUND: Klippel-Feil syndrome (KFS) is characterised by congenital vertebral fusion of the cervical spine and a wide spectrum of associated anomalies. KFS has often been considered a sporadic syndrome. However, since the publication of the original KFS classification early this century, a number of KFS families have indicated heterogeneity complicated by a broad range of variable expression. OBJECTIVE: The two major objectives of this study were (1) to identify differences and similarities in the postnatal appearance, morphology, position and inheritance of vertebral fusions within and between KFS families and (2) to establish a new KFS classification focussed on KFS aetiology. MATERIALS AND METHODS: Vertebral fusions were assessed via spinal radiography. Chromosomal karyotypes were performed using routine cytogenetics. RESULTS: The medical histories of three KFS families are presented. The postnatal time, position and appearance of vertebral fusions, associated anomalies and mode of inheritance were different for the three KFS families. Four classes of KFS are described in a comprehensive classification table that allays much of the uncertainty arising from KFS heterogeneity and variable expression. CONCLUSION: We have described four different KFS classes (KF1-4) within a comprehensive classification that addresses KFS genetic heterogeneity. The position of vertebral fusions in the cervical spine and their incidence within affected families are delineating features of KFS.

Congenital malformations of the craniovertebral junction: classification and surgical treatment.

The clinical, radiological and surgical findings of 56 patients with congenital malformations of the craniovertebral junction who underwent surgical intervention in the Department of Neurosurgery, Hacettepe University Medical School were reviewed. The anomalies were classified according to their embryonic origin. Forty-two cases of the series were major abnormalities formed by the combination of more than one germ layer.

Klippel-Feil syndrome.

Nurses working with orthopaedic clients and pediatric populations may be the first to recognize the classic triad of Klippel-Feil syndrome: short neck, limitation of neck motion, and low occipital hairline. Klippel-Feil syndrome is a congenital malformation of the cervical vertebrae, with limited treatment options. Client/family education is vital to monitor and maintain function and to prevent neurologic deficits resulting from the fusions, accidents, or trauma.

Spinal abnormalities and the atypical form of the Mayer-Rokitansky-Küster-Hauser syndrome.

In 96 patients with congenital absence of the uterus and upper vagina, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, it proved possible to distinguish between the typical and the atypical form using laparoscopy. The typical form was characterized by symmetrical nonfunctioning muscular buds (the Müllerian duct remnants) and normal fallopian tubes, and the atypical form by aplasia of one or both buds, one bud smaller than the contralateral one, with or without dysplasia of one or both fallopian tubes. The atypical form was found in 52 patients (54.2%). Radiographs of the spine showed that congenital spinal abnormalities, especially the Klippel-Feil (KF) syndrome, were seen in 14 of the 52 patients with the atypical form only. Renal agenesis or ectopia together with the MRKH and KF syndromes, known as the MURCS association (MU: Müllerian duct aplasia; R: renal agenesis/ectopia; CS: cervical somite dysplasia), was diagnosed in 10/52 patients in the atypical group. From our results we conclude that additional cervical spine films in patients with the MRKH syndrome are indicated only in the atypical form the syndrome. In those cases where the MRKH syndrome is associated with the KF syndrome, the MURCS association should be considered.

Klippel-Feil anomaly with sacral agenesis: an additional subtype, type IV.

This report describes a child with the Klippel-Feil anomaly and sacral agenesis. A review of the literature revealed that this association has been recorded on other occasions. We believe that this combination of findings is significant and thus propose to call this the Klippel-Feil anomaly type IV.

Klippel-Feil syndrome in children: clinical features and management.

A retrospective analysis of 11 children with the diagnosis of Klippel-Feil syndrome treated at the University of Minnesota Hospital over a period of 20 years is presented. The salient features of the syndrome and its associated anomalies are reviewed. Emphasis is placed on its neurological aspects, particularly the potential risks of injury to the craniocervical junction and cervical spine. Guidelines for the management of these patients are suggested.