Schwartz-Jampel syndrome with gastroduodenal bleeding.

Schwartz-Jampel syndrome is a rare autosomal recessive disorder with joint contractures, generalized myotonia, skeletal anomalies, and facial dysmorphism. The patients with Schwartz-Jampel syndrome have muscle stiffness and electromyography reveals complex, repetitive discharges as myotonic discharges. It is unusual for a Schwartz-Jampel syndrome case to have recurrent gastrointestinal bleeding episodes. The stable endothelial barrier is provided by perlecan which is an important component of vascular structures. Thus, perlecan deficiency may cause recurrent gastroduodenal bleeding. Our report is unique with being the first reported Schwartz-Jampel syndrome case with gastrointestinal bleeding.

Introduction

Schwartz–Jampel syndrome is a rare autosomal recessive disorder with dysmorphic features, skeletal anomalies, and joint contractures leading to delayed milestones.[1] Muscle stiffness and weakness with hypertrophy are the most striking findings.[23] The diagnosis is based on clinical features. Muscle biopsy reveals myopathic changes and electromyography (EMG) reveals complex, repetitive discharges.[24] Genetic analysis reveals mutation of the heparan sulfate proteoglycan 2 (HSPG2) gene which encodes perlecan protein.[13] The stable endothelial barrier is provided by perlecan which is an important component of vascular structures.[56] Recurrent gastroduodenal bleeding is not a previously reported feature. Thus perlecan deficiency in Schwartz–Jampel syndrome patients may cause recurrent gastroduodenal bleeding. Here, we report first Schwartz–Jampel syndrome case with recurrent gastrointestinal bleeding.

Case Report

A 17-month-old girl with recurrent pallid breath holding spells was evaluated. Her mother mentioned that she has had recurrent malodorous and black colored stools until infancy. She was born from consanguineous parents. Her birth weight was 2950 g (<3p) and birth height was 48.5 cm (25–50p). She had respiratory failure and stayed in newborn Intensive Care Unit. She had delay on motor milestones and had the ability of head control at the 4th month and sitting independently when she was 10 months old. She have not had the ability to walk yet. At administration, her weight was 7500 g (<3p) and her height was 71 cm (<3p) indicating postnatal onset short stature. On physical examination pallor skin, tachypnea, sinus tachycardia, dysmorphic features including micrognathia, narrow palpebral fissures, flat face with low hairline, low set ears and full cheeks, short neck, and pectus carinatum, umbilical hernia, joint contractures, axial hypotonia and weakness of extremities with absent deep tendon reflexes, muscle stiffness, hypertrophy of limb muscles were detected. Laboratory tests showed severe iron deficiency anemia (hemoglobin [Hb] 6 g/dL, hematocrit 20%, mean corpuscular volume 49 fL, Fe 1 µg/dL) and mildly elevated creatine kinase (365 U/L) levels. Hb electrophoresis and the other laboratory studies were normal. Chronic gastrointestinal bleeding was found on the research about the etiology of the anemia. Endoscopy was interrupted because of the respiratory arrest side effect of the anesthetics. Repeated fecal occult blood tests were positive. Echocardiography, abdominal ultrasonography, electroencephalography and chromosomal analysis revealed normal findings. Radiological studies revealed multiple skeletal deformities including bowing of tibias and hip dislocation. Clinical diagnosis of Schwartz–Jampel syndrome was made on the basis of typical dysmorphic features and examination findings. Normal nerve conduction studies with repetitive myotonic discharges on EMG confirmed the diagnosis. Breath holdings spells were found to be related to severe iron deficiency which was due to the chronic gastrointestinal loss. Despite the adequate treatment for gastroduodenal bleeding and iron deficiency, mild anemia continued, and melena repeated with longer intervals. Refractory chronic gastroduodenal bleeding with nonspecific cause could be associated with the disruption of basal membrane structure caused by perlecan deficiency in Schwartz–Jampel syndrome. To the best of our knowledge, presence of recurrent gastroduodenal bleeding was not reported in patients with Schwartz–Jampel syndrome.

Discussion

Schwartz–Jampel syndrome is a rare autosomal recessive disorder with dysmorphic features including narrow palpebral fissures, micrognathia, flattened facies, skeletal anomalies, and joint contractures leading to delayed milestones.[1] Muscle stiffness and weakness with hypertrophy are the most striking findings that frequently appear within the first year of life.[23] Genetic analysis reveals mutation of the HSPG2 gene which codes perlecan protein.[13] The diagnosis is based on clinical features. Blood test may reveal mildly elevated creatine kinase. Graphics show skeletal deformities. Muscle biopsy revealed myopathic changes without specific electron microscopic findings. Nerve conduction studies are generally normal and EMG reveals complex, repetitive discharges.[24] Recurrent gastroduodenal bleeding is not a previously reported feature.

The physiological gastroduodenal mucosal defense mechanisms include preepithelial factors (bicarbonate-mucus layer), epithelial barrier with rapid cell renewal with restitution, postepithelial factors (blood supply). Growth factors including epidermal growth factors, fibroblast growth factors (FGF), basal lamina structures (collagen IV, fibronectin…, etc.), may play role in restitution and cell proliferation. Nitric oxide is another important factor which modulates mucosal blood flow and epithelial permability.[567] Stable endothelial barrier provider perlecan is an important component of vascular structures. It interacts with many extracellular matrix components, laminin, collagen Type IV, FGF7…, etc.[6] Nonaka et al. showed that perlecan deficiency may be associated with inactivation of endothelial nitric oxide sentetase expression leading to endothelial dysfunction.[8] Experimental studies revealed that Type IV collagen and perlecan interact with other basal membrane components and provide the stability of basal membrane. Experimental animal and in vivo studies showed that brain and pericardial hemorrhages were related to perlecan or collagen IV gene mutations.[9] Perlecan deficiency induced reduction of vascular endothelial relaxation and basal membrane instability may cause alteration of blood supply of gastroduodenal mucosa leading to recurrent gastroduodenal bleeding.

Conclusion

It should be kept in mind that patients with Schwartz–Jampel syndrome may have weak gastrointestinal mucosal defense mechanisms leading to chronic gastroduodenal blood loss.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.