Beate Schmidt

Association of migraine‐like headaches with Schimke immuno‐osseous dysplasia

Schimke immuno‐osseous dysplasia (SIOD) is characterized by spondyloepiphyseal dysplasia, nephropathy, and T‐cell deficiency. SIOD is caused by mutations in the putative chromatin remodeling protein SMARCAL1. We report an 8‐year‐old boy with SIOD and recurrent, severe, refractory migraine‐like headaches. Through a retrospective questionnaire‐based study, we found that refractory and severely disabling migraine‐like headaches occur in nearly half of SIOD patients. We have also found that the vasodilator minoxidil provided symptomatic relief for one patient. We hypothesize that these headaches may arise from an intrinsic vascular, neuroimmune, or neurovascular defect resulting from loss of SMARCAL1 function.

Serum and Glucocorticoid-Inducible Kinase in Pulmonary Tissue of Preterm Fetuses Exposed to Chorioamnionitis

Objectives: The interaction between inflammation and transepithelial Na+ transport is poorly understood. Chorioamnionitis has been shown to be associated with preterm labor and postnatal pulmonary morbidity of preterm infants. The human isoform of serum and glucocorticoid-inducible kinase (SGK1) is upregulated by proinflammatory cytokines and stimulates epithelial Na+ channel ENaC and the Na+/K+-ATPase activity, an effect presumably participating in the regulation of transepithelial Na+ transport. Study Design: Lung tissue sections from 31 stillborn fetuses (range 21–41 weeks of gestational age) with or without chorioamnionitis were analyzed. Macrophages, neutrophils and lymphocytes were stained immunohistochemically. In addition, in situ hybridization for the detection of SGK1 mRNA was performed in fetal lung tissue. Positively labeled cells were compared by semiquantitative assessment. Results: A marked influx of macrophages into the pulmonary tissue of fetuses exposed to intrauterine inflammation when compared to fetuses without exposure to chorioamnionitis was observed (p < 0.05). There was also a tendency towards an increased density of neutrophils in fetuses exposed to chorioamnionitis. However, only small numbers of lymphocytes were detected in both groups. In fetuses exposed to chorioamnionitis, 6 of 8 fetuses did not express SGK1; however, in the group of fetuses without exposure to intrauterine inflammation 15 of 23 cases exhibited a profound SGK1 detection rate in lung tissue and airway epithelium, independent of the gestational age of the fetuses (p < 0.05). Conclusions: Human serine threonine kinase SGK1 mRNA is observed in fetal lung tissue. On the basis of this study, we speculate that exposure to chorioamnionitis is associated with a downregulation of SGK1 in fetal lung tissue. The possible consequences of a decreased rate of SGK1 mRNA could be an impaired ability to clear the lungs from excessive fluid immediately after preterm birth.

Schimke immunoosseous dysplasia: defining skeletal features

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations. Therefore, we analyzed the skeletal radiographs of 22 patients with and 11 without detectable SMARCAL1 mutations. We found that patients with SMARCAL1 mutations have a spondyloepiphyseal dysplasia (SED) essentially limited to the spine, pelvis, capital femoral epiphyses, and possibly the sella turcica, whereas the hands and other long bones are basically normal. Additionally, we found that several of the adolescent and young adult patients developed osteoporosis and coxarthrosis. Of the 11 patients without detectable SMARCAL1 mutations, seven had a SED indistinguishable from patients with SMARCAL1 mutations. We conclude therefore that SED is a feature of patients with SMARCAL1 mutations and that skeletal features do not distinguish who of those with SED have SMARCAL1 mutations.

Acute glaucoma and intracranial hypertension in a child on long-term peritoneal dialysis treated with growth hormone

A 7-year-old boy with end-stage renal disease on long-term peritoneal dialysis is described. The child developed intracranial hypertension and acute glaucoma during therapy with recombinant human growth hormone (rhGH), 18 months after the onset of treatment. Symptoms developed within 1.5 days and required neurosurgical treatment to reduce the intracranial hypertension because of imminent impaction of the cerebellum and brain stem. After ventricular cerebrospinal fluid drainage and cessation of growth hormone, all symptoms of intracranial hypertension and increased intraocular pressure disappeared. To our knowledge this is the first report of intracranial hypertension or hydrocephalusand acute glaucoma during rhGH therapy. Continuous and long-term control of the ophthalmological and neurological status of patients treated with rhGh is indicated.

Contents Vol. 93, 2008

S. Andersson, Helsinki E. Bancalari, Miami, Fla. G. Buonocore, Siena W.A. Carlo, Birmingham, Ala. V.P. Carnielli, Ancona W.J. Cashore, Providence, R.I. I.A. Choonara, Derby T. Curstedt, Stockholm O. Dammann, Boston, Mass. C. Dani, Florence B. Darlow, Christchurch P. Gluckman, Auckland M. Hallman, Oulu B. Jonsson, Stockholm S.E. Juul, Seattle, Wash. A. Llanos, Santiago R.J. Martin, Cleveland, Ohio C.J. Morley, Melbourne J. Neu, Gainesville, Fla. P.C. Ng, Hong Kong M. Obladen, Berlin A.G.S. Philip, Palo Alto, Calif. M. Post, Toronto E. Saliba, Tours O.D. Saugstad, Oslo B. Schmidt, Hamilton E. Shinwell, Rehovot J. Smith, Cape Town B. Sun, Shanghai H. Togari, Nagoya F. van Bel, Utrecht N. Vain, Buenos Aires M. Vento Torres, Valencia M. Weindling, Liverpool J.A. Widness, Iowa City, Iowa Fetal and Neonatal Research