Down-Klinefelter Syndrome With Concurrent Double Aneuploidy in an Indian Child.

The genetics of Down syndrome (DS) and Klinefelter syndrome (KS) are a nondisjunction of autosomal and sex chromosomes, respectively, resulting in aneuploidies. Less than 70 cases of concurrent Down-Klinefelter syndrome (DS-KS) have been reported in the literature. We report the case of a five-month-old Indian child with a rare double aneuploidy resulting in DS-KS. A five-month-old boy born to non-consanguineously married parents presented with failure to thrive and dysmorphic facies. The family history was unremarkable. On examination, he had an upward eye slant, a depressed nasal bridge, a horizontal crease in the left hand, and a sandal gap. A clinical diagnosis of the Down phenotype was considered. Karyotype analysis revealed the presence of double aneuploidy (48, XXY,+21) suggestive of DS-KS. Down-Klinefelter syndrome presents with the DS phenotype at birth, and the characteristic KS phenotype develops in early infancy and apparently manifests during puberty only. Early diagnosis is required for parental counseling and planning for future pregnancies. In children with a typical Down syndrome phenotype, chromosomal analysis is highly recommended. The diagnosis of DS-KS at the earliest has implications for these children's short-term and long-term outcomes. It helps in planning the subsequent pregnancy with appropriate genetic testing and counseling to avoid the risk of another child with trisomy.

Familial hemiplegic migraine in Indian children-a tertiary center experience.

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1-18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks.

Primary Diffuse Leptomeningeal Melanomatosis in an Indian Child With Review of Literature.

BACKGROUND: Primary diffuse leptomeningeal melanomatosis (PDLM) is an extremely rare, aggressive malignant neoplasia of the central nervous system. We report the first case of pediatric PDLM from India. METHODS: A review of literature was done to describe the 15 pediatric cases reported so far. RESULTS: A 12-year-old male child presented with fever, vomiting, and headache for 2 months. Cerebrospinal fluid examination was normal. An MRI of the brain revealed hydrocephalus, for which antitubercular therapy was started and external ventricular drainage followed by ventriculoperitoneal shunt was done. Repeat MRI revealed a suprasellar lesion, nodular enhancement of cranial nerves along with dural enhancement of spinal cord with arachnoiditis, and long-segment myelomalacia. Repeat cerebrospinal fluid examination was negative for malignant cells. During biopsy, blackish dura with diffuse blackish deposits in ventricle were noted. Histopathological examination revealed tumor cells with intracytoplasmic coarse brown pigment melanoma, frequent mitotic figures, and immunohistochemistry testing was positive for human melanoma black-45 and MelanA, suggestive of PDLM. He expired 4 months after the diagnosis. CONCLUSION: Diagnosing PDLM can be daunting in light of its slow but malignant progression mimicking TBM leading to improper management. However, the absence of any supportive microbiological evidence and failure to respond to the standard antitubercular therapy with subsequent progression of the symptoms should prompt the need for finding an alternative diagnosis. A targeted molecular diagnosis and precision medicine may provide a favorable outcome in children with PDLM.

Teaching NeuroImage: Neuroimaging Features of Wilson Disease.

A 13-year-old boy of nonconsanguineous parents presented with abnormal body movements, gait difficulty, and slurring of speech for 2 years. On examination, he had rigidity, dystonia, dysarthria, and drooling. Ophthalmologic examination revealed bilateral Kayser-Fleischer rings. He had elevated serum "free" copper levels (41.2 µg/dL [range:10-15]), 24-hour urine copper levels (895.7 µg/d [range:<60]), and reduced serum ceruloplasmin levels (4.3 mg/dL (range:20-40]). MRI revealed "face of giant panda" appearance (Figure A), T2-fluid attenuated inversion recovery hyperintensities (Figure, B and C), and frontal cystic encephalomalacic changes (Figure D), suggestive of Wilson disease (WD). Face of giant panda in WD, first described by Hitoshi et al.,1 is due to high signal intensity in tegmentum with normal signals in red nuclei forming the eyes, normal signals of pars reticulata (lateral portion) of substantia nigra forming the ears, and hypointensity of superior colliculus forming the chin.2 Bilateral cystic changes are less commonly reported in WD.3 Recognizing diverse neuroimaging signatures beyond well-known findings in WD enhances diagnostic accuracy.