Elevated Alpha-Fetoprotein in Infantile-Onset Niemann-Pick Type C Disease with Liver Involvement.

Niemann-Pick disease type C (NPC) is a rare autosomal recessive neuro-visceral lipid storage disease. We describe nine cases of infantile-onset NPC with various genetic mutations in the NPC1 gene, which presented with neonatal cholestasis. Serum alpha-fetoprotein (AFP) levels were obtained as part of their workup during the first four months of life. In eight of nine (89%) patients, serum AFP demonstrated elevated levels. Seven infants displayed marked elevations, ranging from 4 to 300 times the upper limit for age-adjusted norms. In most patients, AFP levels peaked during the initial test and declined over time as cholestasis resolved. We conclude that elevated AFP levels are a common, although non-specific, marker for NPC-associated liver disease. These findings demonstrate the benefit of including AFP levels in the workup of neonatal liver disease, especially if there is accompanied cholestasis and if NPC is suspected.

Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects.

Classical xanthinuria is a rare autosomal recessive metabolic disorder caused by variants in the XDH (type I) or MOCOS (type II) genes. Thirteen Israeli kindred (five Jewish and eight Arab) and two isolated cases from Germany were studied between the years 1997 and 2013. Four and a branch of a fifth of these families were previously described. Here, we reported the demographic, clinical, molecular and biochemical characterizations of the remaining cases. Seven out of 20 affected individuals (35%) presented with xanthinuria-related symptoms of varied severity. Among the 10 distinct variants identified, six were novel: c.449G>T (p.(Cys150Phe)), c.1434G>A (p.(Trp478*)), c.1871C>G (p.(Ser624*)) and c.913del (p.(Leu305fs*1)) in the XDH gene and c.1046C>T (p.(Thr349Ileu)) and c.1771C>T (p.(Pro591Ser)) in the MOCOS gene. Heterologous protein expression studies revealed that the p.Cys150Phe variant within the Fe/S-I cluster-binding site impairs XDH biogenesis, the p.Thr349Ileu variant in the NifS-like domain of MOCOS affects protein stability and cysteine desulfurase activity, while the p.Pro591Ser and a previously described p.Arg776Cys variant in the C-terminal domain affect Molybdenum cofactor binding. Based on the results of haplotype analyses and historical genealogy findings, the potential dispersion of the identified variants is discussed. As far as we are aware, this is the largest cohort of xanthinuria cases described so far, substantially expanding the repertoire of pathogenic variants, characterizing structurally and functionally essential amino acid residues in the XDH and MOCOS proteins and addressing the population genetic aspects of classical xanthinuria.

Comparison of Thrombocyte Count Between Pediatric Patients With Migraine or Tension-Type Headache: A Retrospective Cohort Study.

Hypercoagulability may explain the increased risk of thromboembolic cerebrovascular events in patients with migraine. Thrombocytes play a crucial part in the coagulation process, and some studies have demonstrated hyperaggregation of thrombocytes in adult migraineurs. We aimed to compare thrombocyte count between pediatric patients with migraine or tension-type headache and to evaluate the correlation of thrombocyte count with headache parameters. The electronic database of a tertiary pediatric headache clinic was retrospectively searched for all children and adolescents diagnosed with migraine or tension-type headache in 2016-2018. Data on thrombocyte counts were collected from the medical files and compared between the groups by parametric and nonparametric statistical tests. The cohort included 299 patients, 176 girls (59.0%) and 123 (412.0%) boys, of mean age 12.2 ± 3.4 years; 198 had migraine and 101 had tension-type headache. Among the laboratory parameters evaluated, a significantly lower mean thrombocyte number was found in the migraine group than in the tension-type headache group (282 ± 60 vs 304±71 ×103/µL, P = .004). Within the migraine group, there was a significant negative correlation between the thrombocyte count and the duration of headache attacks in hours (P < .05). No significant between- or within-group differences were found in other laboratory parameters. The low relative thrombocyte count in pediatric headache clinic patients with migraine and its negative correlation with duration of migraine suggest that migraine may be associated with a different underlying pathogenesis from tension-type headache.

Cephalic cutaneous allodynia in children and adolescents with migraine of short duration: A retrospective cohort study.

BACKGROUND: Allodynia is prevalent in adults with migraine and has been associated with long disease duration and severe course. Studies of the pediatric population are sparse. The aim of this study was to evaluate the rate of cephalic cutaneous allodynia in children and adolescents within the first 6 months of migraine onset and to identify associated clinical and migraine-related parameters. METHODS: The electronic database of a tertiary pediatric headache clinic from 2014 to 2017 was retrospectively searched for all children and adolescents diagnosed with migraine headache within 6 months or less of symptom onset. Cephalic cutaneous allodynia was identified by validated questionnaire. Demographics, symptoms, and headache-related parameters were compared between patients with and without allodynia. RESULTS: The cohort included 119 patients, 69 girls (58.0%) and 50 (42.0%) boys, of mean age 11.6 ± 3.6 years. Mean time since onset of migraine disease was 3.6 ± 1.8 months. Cephalic cutaneous allodynia was reported by 31.1% of patients. It was significantly associated with female gender ( p = 0.03), older age at admission ( p = 0.037), older age at onset ( p = 0.042) migraine with aura ( p = 0.002), and higher rate of awakening pain ( p = 0.017). CONCLUSIONS: Cephalic cutaneous allodynia may occur in children and adolescents already in the first 6 months of migraine onset. Contrary to adult studies, we found no association of allodynia with migraine frequency or long disease duration. Allodynia was significantly associated with migraine with aura, female gender, and awakening pain. A genetic tendency may contribute to the appearance of allodynia in the pediatric age group.

Thrombophilia Testing in High Pediatric Migraine Risk Children With Migraine.

This study sought to investigate the need for thrombophilia screening in pediatric migraineurs. The cohort included 45/824 children (5.5%) aged 3-18 years with migraine who were tested for thrombophilia at a tertiary pediatric headache clinic. Results were analyzed by background factors and indications for screening. Rates of thrombotic factors were compared with a healthy historical control group. At least 1 thrombotic factor was positive in 19/45 patients (42%). The total thrombophilia risk rate was higher in patients with aura (n = 32). Lipoprotein(a) was the factor most often abnormal in the thrombophilia group of all factors tested (8/19, 42%), regardless of migraine type or gender. It was the only factor with a significantly higher prevalence in the migraine than the historical control group. Full thrombophilia testing in migraine in pediatric headache clinics does not seem to be justified. The high prevalence of elevated lipoprotein(a) in children with migraine warrants further investigation.

Mycobacterium marinum: a rare cause of chronic lymphocutaneous syndrome.

We investigated the prevalence of Mycobacterium marinum lymphadenitis and describe 4 children with the disease. The database of the microbiology laboratory of a tertiary pediatric medical center was searched for all cases of nontuberculous mycobacterial lymphadenitis from 1996 to 2016. M. marinum lymphadenitis was defined as isolation of the pathogen from a lymph node or from a skin lesion with an enlarged regional lymph node. M. marinum was isolated from lymph nodes in 2 of 167 patients with nontuberculous mycobacterial lymphadenitis and from skin lesions in 2 children with skin lesions and regional reactive lymphadenitis, yielding a 2.4% prevalence of M. marinum lymphadenitis. All 4 affected children were younger than 7 years and had been referred for evaluation of enlarged lymph nodes. Preauricular/submandibular and inguinal lymph nodes (n = 2 each) were involved. Three patients had skin traumas and visited the same natural spring. The diagnosis was delayed because a history of aquatic exposure was initially missed. Two children were managed with anti-mycobacterial antibiotics and 2 by observation only. All showed good resolution. CONCLUSION: A detailed history, specifically regarding exposure to spring water sources, in cases of lymphocutaneous syndrome can point to the diagnosis of M. marinum infection. What is Known: • M. marinum can cause chronic nodular or ulcerative skin infections. • Lymphadenitis due to M. marinum has rarely been reported. What is New: • M. marinum infection can present as isolated chronic lymphadenitis; it accounts for about 2.4% of all cases of nontuberculous mycobacterial lymphadenitis and it tends to occur in noncervicofacial regions relative to infections of other nontuberculous mycobacterial species. • Careful history taking including water source exposure, especially in association with skin trauma, can point to the correct diagnosis in children with chronic lymphadenitis.

[TRMU MUTATIONS - REVERSIBLE INFANTILE LIVER FAILURE OR MULTISYSTEM DISORDER?]

INTRODUCTION: Bi-allelic mutations in the TRMU gene cause reversible infantile liver failure. Little is known about extra-hepatic manifestations in these patients. BACKGROUND: Two infants, aged 4 and 5 months, presented with progressive life threatening liver failure, characterized by lactic acidosis, highly elevated alpha-fetoprotein and recurrent hypoglycemia. Both showed significant extra-hepatic findings, including: hypothyroidism, macrocytic anemia and microcephaly. Both were of Jewish Yemenite descent and homozygous for Y77H mutation in the TRMU gene. CONCLUSIONS: TRMU bi-allelic mutations cause severe life-threatening liver failure. Extra-hepatic involvement is common and should be evaluated. Spontaneous resolution and recovery occurs in most patients with a remarkably good long-term prognosis. Liver failure in a Jewish-Yemenite infant should prompt early genetic testing for TRMU Y77H mutation. Pediatricians should be aware of this disease and the common mutation in Israel. DISCUSSION: Nineteen additional patients were described in the literature, of whom 13 were from Israel; 6/19 (31%) manifested extra-hepatic involvement, namely: myopathic weakness, cardiomyopathy, renomegaly and proteinuria, bulbar dysfunction, cerebral white matter changes and abnormal growth including microcephaly. Mortality was 24% (5/21). Survivors (16/21, 76%) showed complete recovery and resolution of clinical, laboratory and histologic abnormalities. Most Israeli patients (10/15) were of Jewish-Yemenite ancestry. Homozygous Y77H genotype was exclusive to this patient subgroup and was associated with a 100% survival and recovery rate.

Younger Age of Migraine Onset in Children Than Their Parents: A Retrospective Cohort Study.

Migraine is known to run in families and has long been considered a strongly heritable disorder. We sought to investigate the age of onset of migraine between successive generations. Our retrospective cohort included 102 children with migraine who were referred to a pediatric headache clinic and their affected parent(s). Age at migraine onset was significantly lower in the children with a history of maternal or paternal migraine than in their mothers or fathers ( P < .001). In conclusion, data on parental history of migraine showed that children with migraine were significantly younger at first appearance of the disease than their affected parents.

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.

BACKGROUND: Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. METHODS: We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis, in whom no underlying etiology had been previously established. RESULTS: Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: (1) disorders of fatty acid metabolism (CPT2), (2) disorders of glycogen metabolism (PFKM and PGAM2), (3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and (4) disorders of purine metabolism (AHCY). CONCLUSIONS: Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

Symptoms and clinical parameters of pediatric and adolescent migraine, by gender - a retrospective cohort study.

BACKGROUND: The available data on gender differences in clinical migraine parameters among pediatric patients are based on relatively few studies, which did not use the current version of the International Classification of Headache Disorders (ICHD) of the International Headache Society. The aim of the present study was to compare between males and females, demographic and clinical characteristics of children and adolescents with migraines diagnosed according to the ICDIII-beta version. METHODS: The electronic database of a tertiary pediatric headache clinic was searched for all children and adolescents diagnosed with migraine headaches in 2010-2016. Data on demographics, symptoms, and headache-related parameters were collected from the medical files. Findings were compared by gender. RESULTS: The cohort included 468 children and adolescents of mean age 11.3 ± 3.6 years; 215 males (45.9%) and 253 females (54.1%). Migraine without aura was documented in 313 patients (66.9%), and migraine with aura in 127 (27.1%); 28 patients (6.0%) had probable migraines. The female patients had significantly higher values than the male patients for the following parameters: age at admission (p = 0.042, Cohen's d 0.8303, 95% CI 0.614-0.992); age at migraine onset (p = 0.021, Cohen's d 0.211, 95% CI 0.029-0.394); rate of migraine with aura (OR 2.01, 95% CI 1.29-3.16, p = 0.0056); headache frequency (p = 0.0149, Cohen's d 0.211, 95% CI 0.029-0.3940); rate of chronic migraine (p = 0.036, OR 1.54, 95% CI 1.02-2.34); and puberty (OR 3.51, 95% CI 2.01-6.35, p = <0.001). Males had a higher rate of vomiting (OR 0.62, 95% CI 0.41-0.93, p = 0.018). Further analysis by pubertal stage revealed that pubertal females, but not prepubertal females, had a significantly higher rate of migraine with aura than did males (41.1% versus 28.9%; OR 1.42, 95% CI 0.85-2.37, p = 0.039). CONCLUSION: Female children and adolescents with migraine treated in a tertiary pediatric headache clinic were characterized by a higher rate of chronic migraine and migraine with aura, a lower rate of vomiting, and older age at onset relative to males. These findings might be influenced by the better description of migraine symptoms by females owing to their better verbal ability.

Vomiting and migraine-related clinical parameters in pediatric migraine.

OBJECTIVE/BACKGROUND: To investigate the characteristics of vomiting in pediatric migraineurs and the relationship of vomiting with other migraine-related parameters. METHODS: The cohort included children and adolescents with migraine attending a headache clinic of a tertiary pediatric medical center from 2010 to 2016. Patients were identified by a retrospective database search. Data were collected from medical files. The presence of vomiting was associated with background and headache-related parameters. RESULTS: The study group included 453 patients, 210 boys (46.4%) and 243 girls (53.6%), of mean age 11.3 ± 3.7 years. Vomiting was reported by 161 patients (35.5%). On comparison of patients with and without vomiting, vomiting was found to be significantly associated with male gender (54% vs 42.1%, P < .018), younger age at migraine onset (8.0 ± 3. years vs 9.6 ± 3.7 years, P < .001), younger age at clinic admission (10.5 ± 3. years vs 11.6 ± 3.6 years, P = .002), higher rate of awakening headache (64.1% vs 38.7%, P < .001), lower headache frequency (10.5 ± 10.3 headaches/month vs 15.0 ± 11.7 headaches/month, P < .001), higher rate of episodic vs chronic migraine (67% vs 58.7%, P < .001), and higher rates of paternal migraine (24.1% vs 10.1%, P < .001), migraine in both parents (9.3% vs 3.1%, P = .007), and migraine in either parent (57.5% vs 45.5%, P = .02). CONCLUSIONS: The higher rate of vomiting in the younger patients and the patients with awakening pain may be explained by a common underlying pathogenetic mechanism of vomiting and migraine involving autonomic nerve dysfunction/immaturity. The association of vomiting with parental migraine points to a genetic component of vomiting and migraine. It should be noted that some of the findings may simply reflect referral patterns in the tertiary clinic.

Comparison of comorbidities of migraine and tension headache in a pediatric headache clinic.

Objective To compare comorbidities between migraine and tension headache in patients treated in a tertiary pediatric headache clinic. Methods Files of patients with migraine or tension headache attending a pediatric headache clinic were retrospectively reviewed for the presence of organic comorbidities. Additionally, patients were screened with the self-report Strengths and Difficulties Questionnaire to identify nonorganic comorbidities. If necessary, patients were referred to a pediatric psychiatrist, psychologist or social worker for further evaluation. Results The study cohort comprised 401 patients: 200 with migraine and 201 with tension headache. The main organic comorbidities were atopic disease, asthma, and first-reported iron-deficiency anemia; all occurred with statistical significance more often with migraine than with tension headache (Familial Mediterranean fever was six times more frequent in the migraine group than in the tension headache group, but the difference was not statistically significant. Nonorganic comorbidities (psychiatric, social stressors) were associated significantly more often with tension headache than with migraine (48.3% versus 33%; p = 0.03). Conclusions Children and adolescents with migraine or tension headache treated in a dedicated clinic have high rates of organic and nonorganic comorbidities. In this setting, patients with migraine have significantly more organic comorbidities, and patients with tension headache, significantly more nonorganic comorbidities.

Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a MICOS complex subunit.

The mitochondrial inner membrane possesses distinct subdomains including cristae, which are lamellar structures invaginated into the mitochondrial matrix and contain the respiratory complexes. Generation of inner membrane domains requires the complex interplay between the respiratory complexes, mitochondrial lipids and the recently identified mitochondrial contact site and cristae organizing system (MICOS) complex. Proper organization of the mitochondrial inner membrane has recently been shown to be important for respiratory function in yeast. Here we aimed at a molecular diagnosis in a brother and sister from a consanguineous family who presented with a neurodegenerative disorder accompanied by hyperlactatemia, 3-methylglutaconic aciduria, disturbed hepatocellular function with abnormal cristae morphology in liver and cerebellar and vermis atrophy, which suggest mitochondrial dysfunction. Using homozygosity mapping and exome sequencing the patients were found to be homozygous for the p.(Gly15Glufs*75) variant in the QIL1/MIC13 (C19orf70) gene. QIL1/MIC13 is a constituent of MICOS, a six subunit complex that helps to form and/or stabilize cristae junctions and determine the placement, distribution and number of cristae within mitochondria. In patient fibroblasts both MICOS subunits QIL1/MIC13 and MIC10 were absent whereas MIC60 was present in a comparable abundance to that of the control. We conclude that QIL1/MIC13 deficiency in human, is associated with disassembly of the MICOS complex, with the associated aberration of cristae morphology and mitochondrial respiratory dysfunction. 3-Methylglutaconic aciduria is associated with variants in genes encoding mitochondrial inner membrane organizing determinants, including TAZ, DNAJC19, SERAC1 and QIL1/MIC13.

Factors Influencing Response to Pharmacologic Treatment of Migraine in a Pediatric Headache Clinic.

OBJECTIVE: The responses of different patients to the same drug may vary as a consequence of biologic, psychosocial, and genetic differences. The aim of this study was to identify clinical factors associated with a response to pharmacologic treatment in pediatric patients with migraine. METHODS: The medical files of patients with migraine attending the headache clinic of a tertiary pediatric medical center in 2010-2015 were reviewed. The children and parents (or only the parents if the child was very young) completed the International Headache Society-based questionnaire. Patients were treated with at least one of the following medications: propranolol, amitriptyline, topiramate. Response to treatment was rated as no change in migraine pattern (grade 1) or a decrease in migraine attack frequency per month by at least 50% (grade 2) or at least 75% (grade 3). The highest-grade response to any pharmacologic treatment was defined as the best clinical response. RESULTS: The study group included 248 patients of mean age 12.71 ± 3.04 years. A grade 3 best clinical response was significantly associated with a positive maternal history of migraine, younger age at treatment onset, lower frequency of headache attacks per month, postpubertal children had a significantly lower rate of grade 3 response than prepubertal children (P < .05). Analysis of the association of overuse of medication and treatment response achieved a P value equal to .05. CONCLUSIONS: Several background and clinical factors are identified that may predispose children with migraine to respond better to pharmacologic treatment. Clinicians who see children with migraine in a pediatric headache clinic setting should consider these factors before initiating a treatment program.

Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency.

OBJECTIVE: To define phenotypic groups and identify predictors of disease severity in patients with phosphoglucomutase-1 deficiency (PGM1-CDG). STUDY DESIGN: We evaluated 27 patients with PGM1-CDG who were divided into 3 phenotypic groups, and group assignment was validated by a scoring system, the Tulane PGM1-CDG Rating Scale (TPCRS). This scale evaluates measurable clinical features of PGM1-CDG. We examined the relationship between genotype, enzyme activity, and TPCRS score by using regression analysis. Associations between the most common clinical features and disease severity were evaluated by principal component analysis. RESULTS: We found a statistically significant stratification of the TPCRS scores among the phenotypic groups (P < .001). Regression analysis showed that there is no significant correlation between genotype, enzyme activity, and TPCRS score. Principal component analysis identified 5 variables that contributed to 54% variance in the cohort and are predictive of disease severity: congenital malformation, cardiac involvement, endocrine deficiency, myopathy, and growth. CONCLUSIONS: We established a scoring algorithm to reliably evaluate disease severity in patients with PGM1-CDG on the basis of their clinical history and presentation. We also identified 5 clinical features that are predictors of disease severity; 2 of these features can be evaluated by physical examination, without the need for specific diagnostic testing and thus allow for rapid assessment and initiation of therapy.

Persistent Headache and Cephalic Allodynia Attributed to Head Trauma in Children and Adolescents.

The aim of the study was to investigate clinical features of headache associated with minor versus moderate to severe traumatic brain injury and of posttraumatic versus primary headache in children and adolescents. Study group included 74 patients after mild (n = 60) or moderate to severe (n = 14) traumatic brain injury identified by retrospective review of the computerized files of a tertiary pediatric headache clinic. Forty patients (54%) had migraine-like headache, 23 (31.1%) tension-like headache, and 11 (14.9%) nonspecified headache. Fourteen patients (53.8%) had allodynia. In comparison with 174 control patients, the study group had a significantly lower proportion of patients with migraine-like headache and a higher proportion of male patients and patients with allodynia. There was no statistically significant correlation of any of the clinical parameters with the type or severity of the posttraumatic headache or rate of allodynia. The high rate of allodynia in the study group may indicate a central sensitization in posttraumatic headache.

Long-term Follow-up of Observation-Only Management of Nontuberculous Mycobacterial Lymphadenitis.

A total of 21 children with clinically and microbiologically proven craniofacial nontuberculous mycobacterial lymphadenitis managed by observation only at a tertiary medical center in 1993-2005 were evaluated for scar parameters at least 2 years after diagnosis. Parents completed a satisfaction questionnaire. Median follow-up time from presentation was 6.8 years (range = 2.3-16.9 years). In all, 18 patients showed scar formation, for a total of 26 scars; 21 scars (81%) had a maximal length of ≤3 cm. Vascularity was normal in 20 scars (77%), and pigmentation was normal in 18 (69%); 21 scars (81%) had a normal to only mildly uneven surface. Although 8 parents (44%) reported that the presence of the scar disturbed them, all responders but one (94%) expressed overall contentment of observation only as a conceivable management alternative. In conclusion, an observation-only approach to craniofacial nontuberculous mycobacterial lymphadenitis is associated with an acceptable outcome and may be an alternative to patients who wish to avoid surgery.

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome.

Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebrofacial syndrome, Cerebro-oculo-facio-skeletal syndrome, Kahrizi syndrome and others. Using exome sequencing, we have been able to identify homozygous mutation p.(Tyr39Cys) in MED25 as the cause of a syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability in seven patients from four unrelated families, all originating from the same village. The protein encoded by MED25 belongs to Mediator complex or MED complex, which is an evolutionary conserved multi-subunit RNA polymerase II transcriptional regulator complex. The MED25 point mutation is located in the von Willebrand factor type A (MED25 VWA) domain which is responsible for MED25 recruitment into the Mediator complex; co-immunoprecipitation experiment demonstrated that this mutation dramatically impairs MED25 interaction with the Mediator complex in mammalian cells.

Association of pediatric obesity and migraine with comparison to tension headache and samples from other countries.

The link between body weight and headache has hardly been examined in children. The aim was to evaluate the association of obesity and migraine in selected pediatric patients and compare the findings with the literature. Data on clinical symptoms, headache type, and body mass index standard deviation score were derived from the medical files of 245 patients with migraine and 87 with tension headache. Comparison of the 3 subgroups of migraine patients of normal weight, overweight, and obese with the corresponding body mass index standard deviation score subgroups of patients with tension-type headache yielded no statistically significant differences in frequency of headache attacks per month, or duration of headache attacks in hours. These results call into question earlier reports linking headache and obesity in children. Differences in findings between our study and those in the literature highlight several factors that should be addressed in further studies. A larger sample size may reveal more significant results.

Association of age at onset of migraine with family history of migraine in children attending a pediatric headache clinic: a retrospective cohort study.

AIM: Migraine is known to run in families and has long been considered a strongly heritable disorder. This study sought to evaluate the relationship between age at onset of pediatric migraine and family history of migraine. METHODS: Review of the medical files of the headache clinic of a tertiary pediatric medical center yielded 344 children with migraine for whom details on migraine in family members were available. RESULTS: Mean age of the cohort was 11.69 ± 3.49 years, and mean frequency of headache per month, 13.68 ± 11.26. Mean age at migraine onset in patients with a negative parental history was10.48 ± 3.39 years; in patients with one parent with migraine, 8.84 ± 3.72 years; and in patients with both parents with migraine, 7.32 ± 3.22 years (p < 0.001).The duration of migraine attacks (in hours) was significantly longer in patients with any family member with migraine than in those with no family history (p = 0.026). CONCLUSIONS: Among children attending a tertiary pediatric headache clinic, migraine appears at a younger age in those with parental history of migraine than in those with a negative family history. The findings suggest that having a genetic background of migraine makes a child more susceptible to migraine earlier in life than a child without a family history.