The following conclusions were reached: 1) brain damage in MCT8 deficiency is diffuse, without evidence of focal lesions, and present from fetal stages despite apparent normality at birth; 2) deficient hypomyelination persists up to 11 years of age; and 3) the findings are compatible with the deficient action of thyroid hormones in the developing brain caused by impaired transport to the target neural cells.

Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal atresia (EA) patients. A retrospective case analysis of all EA patients born at our center between January 1999 and April 2012 was performed. A total of 113 of patients were identified; 10 patients were excluded as a result of inadequate data. Eighteen patients (17%) were diagnosed with EoE. The average number of eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months). Children with EoE had a significantly greater incidence of reflux symptoms, dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also underwent significantly more surgery including fundoplication and aortopexy when compared with those without EoE (P < 0.0001). Although the incidence of gastrostomy was greater in the EoE group (33% vs. 13%), this was not statistically significant. Half of the EoE patients had a coexisting atopic condition at time of diagnosis. The commonest condition was asthma 7/18 (38%) followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with either swallowed fluticasone or budesonide slurry. All improved clinically. Histologically, five had complete resolution and six had partial improvement. Six children with EoE were treated with acid suppression alone. All improved clinically, and 5/6 had subsequent histological resolution. One child who received acid suppression and an exclusion diet also improved. Seven patients (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at time of the initial endoscopy, prior to the diagnosis of EoE being available. Two patients had resolution of their strictures on medical treatment of their EoE alone and did not require further dilatation. EoE was seen in 17% of children with EA in this study. EoE should be considered in EA patients with persistent symptoms on standard reflux treatment, increasing dysphagia, and recurrent strictures.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Non-pulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and ten deletions, we have identified an additional thirty eight novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, twenty missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic whereas four familial cases with three showing maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA binding domain, indicating its plausible role in gene regulation. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis worldwide. We describe 2 cases among young children from Sydney, Australia, where locally acquired infection of children has not been reported previously. Both cases manifested as severe hemorrhagic meningoencephalitis, one resulting in death. Angiostrongyliasis must be considered in acute neurological presentations occurring among individuals who live in endemic areas.

We report a case of a 2 year-old boy who initially presented with macrocephaly and severe global developmental delay. Imaging revealed a large left temporo-parietal mass that was lobulated, calcified, focally enhancing and partially cystic. A second surgery was required for tumor recurrence approximately one year later, and tissue from that resection proved to be diagnostic for an embryonal tumor with abundant neuropil and true rosettes (ETANTR). Only 12 cases of this rare pediatric embryonal tumor have been previously documented, and as of 2000, the WHO has not recognized ETANTR as a distinct entity (Kleihues P, Cavenee WK (2000) International agency for research on cancer: pathology and genetics of tumors of the nervous system. IARC Press, Lyon). As opposed to prior cases, our patient's tumor exhibited extensive neurocytic elements. Two recently described cases were examined via fluorescence in situ hybridization (FISH), with one demonstrating isochromosome 17q (i17q) and the second exhibiting polysomies of chromosomes 2, 8, 17 and 22 (Fuller C, Fouladi M, Gajjar A, Dalton J, Sanford RA, Helton KJ (2000) Am J Clin Pathol 126: 277-283). Via FISH analysis, we found normal dosages of chromosomes 2, 8 and 17. Our case expands the histopathologic spectrum of ETANTR, illustrating marked neuronal differentiation towards neurocytes. The lack of common PNET-associated FISH abnormalities in this case adds to the limited cytogenetic genetic data on this rare pediatric embryonal neoplasm.

There are very few conditions that present with dopa-responsive juvenile parkinsonism. We present two such children with neuronal intranuclear inclusion disease (NIID) who had an initial good levodopa response that was soon complicated by disabling dopa-induced dyskinesia. One child was diagnosed by rectal biopsy in life, and the other diagnosis was confirmed at postmortem. In this patient, dopamine transporter imaging showed severely decreased binding of the radiotracer in the striatum on both sides. Bilateral subthalamic deep brain stimulation in this patient produced initial improvement, but this was not sustained. Both patients died within 10 years of symptom onset. As well as levodopa responsiveness with rapid onset of dyskinesia, clues to the diagnosis of NIID in patients presenting with parkinsonism include the presence of gaze-evoked nystagmus, early onset dysarthria and dysphagia and oculogyric crises. Differential diagnosis of clinical symptoms and neuropathological findings are discussed including the approach to rectal biopsy for early diagnosis.

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We report three cases of primary osteoma cutis in children, two of whom (siblings) were associated with Albright's hereditary osteodystrophy (AHO), manifesting as short stature with autosomal dominant inheritance from the father, but no dysmorphic features and no parathyroid hormone (PTH) resistance. Osteoma cutis can manifest as an isolated skin disease, a secondary condition to other skin diseases (such as acne), or in association with several syndromes, including AHO, which in turn may be associated with PTH resistance. The management and prognosis of patients diagnosed with osteoma cutis is determined by whether the skin manifestation has occurred in isolation, in association with a syndrome, or as a secondary skin disease. These three paediatric cases highlight the importance of understanding the aetiology and associations of osteoma cutis in order to appropriately investigate and manage patients who present with this rare skin disease.