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Glycogen storage disease IV (GSD IV), caused by a defect in GBE1, is a clinically heterogeneous disorder. A classical hepatic form and a neuromuscular form have been described. The severe neuromuscular form presents as a fetal akinesia deformation sequence or a congenital subtype. We ascertained three unrelated families with fetuses/neonates who presented with fetal akinesia deformation sequence to our clinic for genetic counseling. We performed a detailed clinical evaluation, exome sequencing, and histopathology examination of two fetuses and two neonates from three unrelated families presenting with these perinatally lethal neuromuscular forms of GSD IV. Exome sequencing in the affected fetuses/neonates identified four novel pathogenic variants (c.1459G>T, c.144-1G>A, c.1680C>G, and c.1843G>C) in GBE1 (NM_000158). Histopathology examination of tissues from the affected fetuses/neonate was consistent with the diagnosis. Here, we add three more families with the severe perinatally lethal neuromuscular forms of GSD IV to the GBE1 mutation spectrum.

Objectives: The aim of this study was to evaluate whether high-resolution brachial plexus (BP) magnetic resonance neurography (MRN) is capable of (1) distinguishing patients with compressive neuropathy or noncompressive plexopathy from age- and sex-matched controls, (2) discriminating between patients with compressive neuropathy and noncompressive plexopathy, and (3) detecting spatial lesion patterns suggesting somatotopic organization of the BP., Materials and Methods: Thirty-six patients (50.9 ± 12.7 years) with clinical symptoms, nerve conduction studies, and needle electromyography findings suggestive of brachial plexopathy and 36 control subjects matched for age and sex (50.8 ± 12.6 years) underwent high-resolution MRN of the BP. Lesion determination and localization was performed by 2 blinded neuroradiologists at the anatomical levels of the plexus trunks and cords., Results: By applying defined criteria of structural plexus lesions on high-resolution MRN, all patients were correctly rated as affected, whereas 34 of 36 controls were correctly rated as unaffected by independent and blinded reading from 2 neuroradiologists with overall good to excellent interrater reliability. In all cases, plexopathies with a compressive etiology (n = 12) were correctly distinguished from noncompressive plexopathies with inflammatory origin (n = 24). Pathoanatomical contiguity of lesion from trunk into cord level allowed recognition of distinct somatotopical patterns of fascicular involvement, which correlated closely with the spatial distribution of clinical symptoms and electrophysiological data., Conclusions: Brachial plexus MRN is highly accurate for differentiating patients with symptomatic plexopathy from healthy controls and for distinguishing patients with compressive neuropathy and noncompressive plexopathy. Furthermore, BP MRN revealed evidence for somatotopic organization of the BP. Therefore, as an addition to functional information of electrodiagnostic studies, anatomical information gained by BP MRN may help to improve the efficiency and accuracy of patient care.

Rationale: Hereditary neuropathy with liability to pressure palsy (HNPP) is an episodic, multifocal neuropathy, with a typical clinical presentation of recurrent transient pressure palsies, which is induced by a PMP22 deletion. Another neuropathy caused by a PMP22 duplication is Charcot-Marie-Tooth disease type 1A (CMT1A). PMP22 is a gene coding a protein called peripheral myelin protein 22 (PMP22), which plays an essential role in the formation and maintenance of compact myelin. Coexistence of type 2 diabetes mellitus (T2DM) and CMT1A has been reported in many work, however HNPP patients with T2DM are rare, and comorbidity of HNPP and psoriasis has not been reported previously. Electrophysiological features of HNPP has been found progressing with aging. Patient concerns: Here we present a 20-year-old man who exhibited lower extremity weakness and foot drop as the initial manifestation., Diagnoses: HNPP was diagnosed on the basis of clinical features, positive sural nerve biopsy findings, and genetic testing results. Moreover, physical examination, blood/urine glucose test, and diabetes-related autoantibodies investigations demonstrated that he had psoriasis and T2DM. The electrophysiological manifestations revealed profound demyelinating injuries and axonal injuries in distal peripheral nerves and facial nerves, which were more severe than general HNPP cases., Interventions: The young patient was treated with continuous subcutaneous insulin infusion and blood glucose monitoring, and then transferred to oral acarbose therapy. The psoriatic lesions were treated with calcipotriol ointment., Outcomes: In the follow-up, the right leg weakness was alleviated, and his gait was improved., Lessons: The findings indicate that diabetes mellitus may have an impact on the severity of HNPP. Physicians should consider that worsening of symptoms might result from newly diagnosed diabetes mellitus while treating patients with HNPP.

The majority of previous studies on hereditary neuropathy with liability to pressure palsies (HNPP) were focused on peripheral nerves, whereas cerebral alterations in HNPP have been less attended to. In this work, Diffusion tensor imaging (DTI) was used to detect the changes in WM, especially in the normal-appearing white matter (NAWM) in HNPP patients for its sensitivity in probing the microstructure of WM, the sensitive metric was searched for probing cerebral alterations and the regional distribution of cerebral abnormalities was identified. Twelve HNPP patients and 12 age- and gender-matched healthy controls underwent the conventional MRI, DTI scan, and electrophysiological examination. The conventional MRI images were first analyzed to identify abnormal intense regions and the NAWM regions. NAWM refers to the white matter regions that do not include the lesions on conventional MRI. The apparent diffusion coefficient and fractional anisotropy (FA) values of the NAWM were then measured and compared between patient and control groups. The sensitivity and specificity of 3 methods and the cerebral regional distribution of MR signal abnormalities were further analyzed. Hyperintense foci were observed on T2 weighted image and fluid attenuated inversion recovery images in 6 patients. Compared to the controls, FA values of the patients were significantly lower in bilateral frontal, orbitofrontal, and temporal NAWMs; whereas the electrophysiological examination results of patients and controls exhibited no statistically significant difference. The sensitivity of FA value was higher than that of electrophysiological examination and conventional MRI. The majority of abnormal signals on conventional MRI images and abnormal FA values were located in the frontal and temporal lobes. The results of our study show cerebral WM changes in HNPP patients. FA value in DTI has been shown to be sensitive to the cerebral microstructural changes in HNPP. The frontal lobe is the predilection site that is most involved in HNPP.

Background: Treatment of foot deformities in arthrogryposis is a challenging problem. Most deformities are very rigid clubfeet, such as deformities with severe equinus, supination, cavus, hindfoot varus, and forefoot adduction. Vertical talus with severe rocker bottom is also common. Traditional approaches included casting and soft tissue release, which are usually only partially successful. We describe our experience with the treatment of arthrogrypotic foot deformities with the Taylor Spatial Frame., Methods: Over a period of 5 years, we treated 7 patients (10 feet) with various arthrogrypotic foot deformities. There were 4 girls and 3 boys with a mean age 10.6 years (range: 4 to 16 y). Six patients had clubfoot deformities and 1 had vertical talus. All patients had previous surgeries, including soft tissue release in 8 feet and Ilizarov correction in 3 feet. Three patients underwent bilateral correction, 3 patients underwent midfoot osteotomies, and 2 patients had supramalleolar osteotomies and lengthening to compensate for growth arrest of the distal tibia. The remaining feet had correction of their deformities by soft tissue distraction. Six patients underwent correction using a Butt frame and 5 by standard frame configuration., Results: All patients achieved the preoperative correction goal and their frames were removed at an average of 16.1 weeks (range: 14 to 18 wk). Complications included pin tract infections in 4 patients. One patient had iatrogenic regenerate translation that was reduced by a residual program, 1 patient had recurrence of equines, and another had partial recurrence of forefoot supination. Two hindfoot varus deformities were successfully treated by calcaneal osteotomy at the time of Butt frame removal., Conclusions: On the basis of our preliminary experience, we believe that the Taylor Spatial Frame is a reliable and accurate method of correction of complex foot deformities in children with arthrogryposis.

Background: The term arthrogryposis is a descriptive term referring to a variety of clinical conditions characterized by multiple joint contractures. The spine may be involved; however, the presence of associated congenital vertebral abnormalities is rare., Methods: A retrospective chart review of 6 patients with asymmetric upper extremity joint contractures and concomitant congenital scoliosis of the cervical spine was performed., Results: Six patients with congenital anomalies of the cervical spine and asymmetric contractures of the upper extremities were identified. Clinical findings and radiographic studies were reviewed. Upper extremity involvement was contralateral to the convexity of the spinal curvature in 5 of the 6 cases. Reconstruction of the upper extremity was required in 5 of 6 patients; however, no patient required operative intervention for their congenital cervical scoliosis., Conclusions: Congenital cervical spine anomalies can be associated with asymmetric arthrogryposis of the upper extremities. Physicians who take care of pediatric patients with arthrogryposis should carefully evaluate the cervical spine., Level of Evidence: Level IV, case series.

ARC syndrome, the association of arthrogryposis, renal tubular dysfunction and cholestasis, is a rare genetic disorder. We report two Saudi infants from two different families with ARC syndrome. Magnetic resonance imaging of the brain of one of the infants showed lissencephaly, a previously unreported finding in this syndrome. We also review 39 ARC cases reported in the literature using the Medline database from January 1966 to September 2004.

Renal-coloboma syndrome is a developmental disorder involving optic nerve colobomas and renal hypoplasia/insufficiency, which exhibits autosomal dominant inheritance and a highly variable phenotype (OMIM:120330). Mutation in the PAX2 gene was found to result in the renal-coloboma phenotype. We report on an Arab family with autosomal dominant inheritance of a syndrome characterized by a variable combination of optic nerve colobomas, renal abnormalities, vesicoureteral reflux, lax joints and arthrogryposis multiplex. Apart from the arthrogryposis multiplex which has not been described in the renal-coloboma syndrome, the features of the syndrome in this family are very similar to the renal-coloboma syndrome. However sequencing of all 12 axons of PAX2 gene revealed no mutation in this family. The disorder in this family is likely to represent a new syndrome with features overlapping with the renal-coloboma syndrome.

To determine whether SMNT deletion may be associated with arthrogryposis, we tested DNA extracted from paraffin blocks for deletion of SMNT (exons 7 and 8). Analysis of the DNA showed an SMNT deletion in two of four infants with neurogenic arthrogryposis. In addition to loss of anterior horn cells, patients with SMNT deletion had degeneration of central sensory neurons in Clarke's column and the thalamus. Although one of the patients with no deletion also had cortical pathology, clinical and pathologic characteristics of the two patients without deletion were otherwise similar to the two patients with deletion. Arthrogryposis and degeneration of sensory neurons may be associated with deletion of SMNT.

We describe a 37-week gestational age infant who presented with lethal arthrogryposis multiplex congenita due to complete absence of peripheral nervous system (PNS) myelin. Schwann cells accomplished successful developmental proliferation, migration, axonal ensheathment, basal lamina production, and subsequent cessation of proliferation, but failed in spiral lengthening and longitudinal growth. Internuclear distance was very short, resulting in marked Schwann cell hypercellularity. No supernumerary Schwann cells (onion bulbs) were found. No PNS myelin proteins (P0, P1, MAG) were detected by immunocytochemical methods, and the Schwann cells adopted many morphologic features characteristic of unmyelinated nerves. The defect appears to be an arrest in Schwann cell differentiation at the stages of mesaxon elongation and longitudinal growth.