A 16q12.2q21 deletion identified in a patient with developmental delay, epilepsy, short stature, and distinctive features.

Interstitial deletions of the 16q centromeric region are rarely reported. A microdeletion of the 16q12.2q21 region was identified in a patient with intellectual disability, epilepsy, short stature, and distinctive features; including up-slanting palpebral fissures, hypertelorism, epicanthic folds, anteverted nares, simple philtrum, thin upper lip vermilion, high arched palate, posteriorly rotated ears, and overlapping toes in his right foot. Although the deleted region includes the genes responsible for neurological impairments (GNOA1, GPR56, KATNB1, and BBS2), haploinsufficiency of these genes would not be associated with the patient's phenotype. When NDRG4, present in the deleted region, was knocked out in mice, these mice exhibited spatial learning deficits. Thus, we hypothesize that this gene could be a potential candidate underlying the neurological observations of the patient. Because RSPRY1 was been discovered as the cause of progressive skeletal dysplasia, a loss of this gene might explain the skeletal defects observed in the patient.

Outcome of renal proximal tubular dysfunction with Fanconi syndrome caused by sodium valproate.

BACKGROUND: Although Fanconi syndrome is rare in patients with epilepsy treated with sodium valproate (VPA), the prevalence might be higher in children with severe motor and intellectual disabilities (SMID). VPA-induced Fanconi syndrome usually has a favorable outcome, but the long-term outcome of renal tubular dysfunction in SMID patients remains unknown. The aim of this study was therefore to investigate the long-term outcome of renal proximal dysfunction in SMID children with Fanconi syndrome caused by VPA. METHODS: The records of six children with SMID and Fanconi syndrome caused by VPA were retrospectively reviewed to assess long-term proximal renal tubular function after discontinuation of VPA. All six patients had intractable epilepsy and required tube feeding. RESULTS: Proximal tubular dysfunction improved in almost all patients after VPA discontinuation, although abnormal uric acid reabsorption persisted in three patients. Five patients had hypocarnitinemia. After carnitine supplementation, one of these three patients with decreased ability to reabsorb uric acid had a normal serum level and improved fractional excretion of uric acid. CONCLUSIONS: Secondary carnitine deficiency may cause prolonged tubular dysfunction in some SMID patients with VPA-induced Fanconi syndrome. Fanconi syndrome caused by VPA is a usually reversible dysfunction of the proximal tubules, but can be permanent. Although not effective for all patients, carnitine is recommended for patients with VPA-induced Fanconi syndrome, especially children with SMID.

Rub epilepsy in an infant with Turner syndrome.

We report a case of infantile refractory epilepsy associated with Turner syndrome (TS), showing very frequent, focal clonic seizures of the left upper extremity. Characteristically, in addition to spontaneous fits, her seizure was inducible by rubbing her left hand and forearm for a few seconds. Accordingly, she was diagnosed with a rare form of reflex epilepsy, "rub epilepsy". Neuroradiological investigation indicated the existence of cortical abnormalities, such as focal cortical dysplasia of the right parietal lobe. Patients with TS are reported to have neuroanatomical abnormalities, especially of the parietal lobe. Thus, our case may imply a causal relationship between potential cortical hyperexcitability of the parietal lobe and epilepsy in TS. This is the first reported infantile case of rub epilepsy, and more generally, reflex epilepsy associated with TS.

[Child case of chronic inflammatory demyelinating polyneuropathy showing phagocytic myelinolysis and regenerative changes on electron microscopic analysis of the sural nerve].

We reported a 9-year-old boy with chronic inflammatory demyelinating polyneuropathy (CIDP) showing characteristic electron microscopic study findings on a sural nerve biopsy. He came to our hospital because of muscle weakness progressing slowly for 2 years. He developed distal muscle weakness and areflexia. Cerebrospinal fluid protein was elevated without pleocytosis. Moter conduction velocities were reduced. Partial conduction block and abnormal temporal dispersion were present. The electron microscopic findings on a sural nerve biopsy comprised both active demyelinating lesions, i.e., macrophages were peeling away the myelin lamellae and phagocytosing some myelin debris, and remyelinating lesions with onion bulb formations. Some findings mimic electron microscopic changes in Guillain-Barré syndrome, although tests for the known anti-ganglioside antibodies were negative. So, he was diagnosed as having definite CIDP and prednisolone with gamma-globulin infusion was effective to ameliorate his symptoms.

Secondary renal Fanconi syndrome caused by valproate therapy.

Although renal Fanconi syndrome resulting from valproate (VPA) has occasionally been reported, the detailed clinical characteristics of this disease remain unclear. To clarify the clinical features of patients with VPA-induced Fanconi syndrome, we analyzed the clinical and laboratory data of seven affected patients. All patients were children, were severely disabled and required tube feeding. Five patients required treatment with multiple anticonvulsant agents. Hypophosphatemia and hypouricemia were found in all patients. Mild proteinuria, increased excretion of urinary beta2-microglobulin (beta2MG) and generalized hyperaminoaciduria were present in all patients. The renal biopsy of one patient exhibited tubulointerstitial nephritis without any structural abnormalities of the mitochondria in proximal renal tubular cells. All patients recovered from the Fanconi syndrome after the cessation of VPA therapy without any long-term renal sequellae. These results indicate that young age and being severely disabled with tube feeding and anticonvulsant polytherapy are contributory factors to the development of VPA-induced Fanconi syndrome. Serum phosphate and uric acid concentrations and urinary beta2MG levels in addition to serum electrolytes and urinalysis should be examined regularly in patients receiving VPA therapy, especially in those with the contributory factors outlined above. Patients with Fanconi syndrome caused by VPA have a favorable renal outcome.