Pediatric headache and neuroimaging: experience of two tertiary centers.

INTRODUCTION: Headache is a frequent complaint in children and adolescents. Decision-making for neuroimaging should take into account the cost and the need for sedation in young children. AIM: To evaluate the yield of MRI in pediatric headache patients seen in two large tertiary hospitals. METHODS: Data were retrospectively collected from patient records (n = 613) and neuroimaging reports. Headache was classified according to International Headache Society guidelines. RESULTS: There were 346 children with imaging studies (MRI n = 281, CT n = 65). Of patients who had at least one MRI study, 29% demonstrated an abnormal finding. Findings altering the management were obtained in 21 (7%) patients: the majority (n = 17, 80%) had headache for less than 3 months. On the other hand, four patients with headache longer than 3 months (19%) and 12 patients with normal neurological examination (57%) had significant MRI results affecting management. None of the children in whom the diagnosis of migraine could be made on clinical grounds (n = 40) had a significant MRI finding. CONCLUSION: Neuroimaging should be performed selectively in children with headache seen in pediatric neurology clinics, especially in headache of short duration (< 3 months) and features atypical for migraine. A normal neurological examination should not reassure the clinician.

Vitamin D status in children with headache: A case-control study.

BACKGROUND: Vitamin D is a fat soluble vitamin with hormonal properties, plays crucial functions in bone and mineral metabolism and has important regulatory functions in brain development, cell differentiation and apoptosis. Some studies have shown a link between vitamin D deficiency and headache. MATERIAL AND METHODS: In this study, 147 patients with headache (migraine or either tension-type headache (TTH)) and 69 healthy controls, aged 5 to 16 years, were evaluated. Each group was also divided into two separate sub-groups based on presentation to the clinic in either high solar-exposure (HSE) and low solar-exposure (LSE).We retrospectively evaluated the levels of calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and 25-OH vitamin-D3. Levels below 20 ng/ml were described as vitamin D deficiency and levels of 2030 ng/ml as vitamin D insufficiency. RESULTS: The levels of 25-OH vitamin-D3 were statistically significantly lower when compared to the control group (17.1±9.4 vs. 25.8 ± 12.8 ng/mL, respectively; p < 0.001). This held true for both the HSE and LSE group compared to the control group (for the group 1; 24.6 ± 11.8 vs. 32.1 ± 10.6 ng/mL, respectively; p = 0.007, and for the group 2; 14.5 ± 6.8 vs. 19.6 ± 13.5 ng/mL, respectively; p = 0.003). Also in headache subgroups (migraine and TTH), vitamin D levels were significantly lower than the control group (17.3 ± 9.0, 16.9 ± 9.9 and 25.8 ± 12.8 ng/mL respectively; p < 0.001). CONCLUSION: There may be a relationship between vitamin D deficiency and headache, with particular significance in LSE. We suggest that this conclusion needs to be supported with randomised clinical studies containing a larger numbers of samples and controls.

TWO CASES WITH DIFFERENT EPILEPSY TYPE AND DYSMORPHIC FEATURES ASSOCIATED WITH 17q21.31 MICRODELETION SYNDROME.

The 17q21.31 microdeletion syndrome is characterized by intellectual disability, epilepsy, facial dysmorphism and friendly behavior. Recently, KANSLJ gene has been considered as a major causal gene for this phenotype. Here we report on two Turkish patients with different seizure types and additional dysmorphic features associated with 17q21.31 microdeletion syndrome. A 4 year-old female patient with generalized tonic-clonic seizures, mild mental retardation, dysmorphic features and friendly behavior and a 14 years-old female with intractable epilepsy, different dysmorphic features, severe mental and motor retardation and self-mutilation were evaluated by array-based comparative genomic hybridization (microarray CGH). Array CGH identified 17q21.31 microdeletion that contains MAP7 CRHR1, KANSLI, PLEKHMI genes in case I and CRHR1, PLEKHM but not KANSLJgenes in case 2. To the best of our knowledge this is the first report of a patient with the 17q21.31 microdeletion which does not encompass KANSLI gene. These data imply another gene or genes causing similar phenotype in this patient.

Hemihyperplasia-multiple lipomatosis syndrome associated with hydrocephalus.

Hemihyperplasia-multiple lipomatosis syndrome (HMLS) is characterized by subcutaneous lipomatosis and an asymmetric overgrowth (hemihyperplasia). We report an extremely rare case of HMLS associated with hydrocephalus, emphasizing the clinical features and differential diagnosis.

Array-CGH and clinical findings in a patient with a small supernumerary r(8) mosaicism.

Small supernumerary ring chromosomes (sSRC) represent a subset of small supernumerary marker chromosomes (sSMC) where r(8) is relatively common. The phenotype sSRC(8) ranges from almost normal to variable degrees of abnormalities in mosaic or non-mosaic conditions. We present a new patient of de novo mosaic supernumerary ring chromosome 8 which has trisomy of a region of chromosome 8p11.21-q21.13. Mosaicism for a ring chromosome was showed by routine karyotyping that revealed a karyotype of mos47,XY,+r(?) [47]/46,XY [36] and we performed array comparative genomic hybridization (array-CGH) in order to precisely define the extension about chromosomal origin of the duplicated region in a patient. Array-CGH analysis confirmed that the sSRC derived a 43.921 Mb genomic gain of chromosome 8 (p11.21-q21.13). Common clinical features of the patient included multiple congenital anomalies, developmental delay, thoracolumbar scoliosis, mild pulmonary stenosis, laryngomalacia, hypospadias and atypical facial appearance. With this study a patient involving mosaic trisomy 8p11.21-q21.13 along with clinical properties, is described and compared to previously reported cases involving partial trisomy 8q.

Multiloculated hydrocephalus of intrauterine-onset: a case report of an unexpected MTHFR A1298C positive test result.

Loculated hydrocephalus is a condition in which discrete fluid-filled compartments form in association with the ventricular system of the brain. Multiloculated hydrocephalus is a subgroup of this entity involving more than one segment of the ventricular system. Abnormal descent of the cerebellar components can cause multiloculated hydrocephalus due to various pathogenesis. However, studies report no more than 10% of correlation between cerebellar herniation and hydrocephalus. We report an infant with MTHFR A1298C homozygosity, who had hydrocephalus of intrauterine-onset. Alterations in the folate metabolism might lead to congenital hydrocephalus and there is growing data on the prothrombotic effects of MTHFR polymorphisms. To the best of our knowledge, there has been no reported case of MTHFR A1298C homozygosity and intrauterine-onset multiloculated hydrocephalus as a co-existence in the literature.

Pontocerebellar hypoplasia associated with nevoid hyperpigmentation and dysmorphic findings: a new subtype?

Pontocerebellar hypoplasia consists of a rare heterogeneous group of congenital neurodevelopmental disorders characterized by hypoplasia and atrophy of the cerebellar cortex, dentate and pontine nuclei, and inferior olives. Lineer nevoid hyperpigmentation is a rare skin condition characterized by whorls and streaks of hyperpigmented macules in a reticulate pattern along Blaschko's lines. Herein we present a three year-old male patient with pontocerebellar hypoplasia associated with nevoid hyperpigmentation on the upper part of the body. Besides he has some dysmorphic features including microcephaly, triangular chin, long philtrum, long hand fingers, flexion contracture in all of the distal phalanges of both hands, and strabismus.

Ring chromosome 18 in a child with febrile seizures.

Ring chromosomes are uncommon cytogenetic findings but have meanwhile been reported for nearly all human chromosomes. Among the rare observations of ring chromosomes in man, the diagnosis of ring chromosome 18 represents a prominent group. We here describe on the cytogenetic analysis results obtained for a 9 years old male patient of non-consanguineous parents. He had growth and developmental delay, mental and motor retardation, microcephaly, microphtalmia, triangle face, small dysplastic ears, strabismus, epicanthal folds on the left, short stature, cryptorchidism, spasticity, pes equinovarus, pes planus, hypothroidism, stereotypic movements and febrile seizures. Also he had hypomyelinization and multiple hyperintense focuses within the white matter on the MRI. The generalized epileptiform abnormality originated from bilateral Centroparietal region. The metabolic investigations including blood and urine amino acids and lysosomal screening tests were normal. The chromosome analysis identified [46,XY,r(18)/46,XY] in 35% of cells a ring 18 and in 65% of cells normal karyotype in peripheral blood cells examined by standard G-bands by Trypsin using Giemsa (GTG) analysis. The dysmorphic features of the presented patient are discussed to the identification of the genotype-phenotype correlation related to his karyotype.

Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance.

Monilethrix, a rare autosomal dominant disease characterized by hair fragility and follicular hyperkeratosis, is caused by mutations in three type II hair cortex keratins. The human keratin family comprises 54 members, 28 type I and 26 type II. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the basis of clinical characteristics and microscopic examination in a family with 11 affected members. Haplotype analysis was performed by three Simple Tandem Repeat markers (STR) and KRT86 gene was sequenced for the identification of the disease causing mutation. In the results of this, autosomal dominant mutation (E402K) in exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family from Turkey.