Congenital and acquired anomalies of the basilar artery: A pictorial essay.

INTRODUCTION: The basilar artery is one of the two cases in our body where an arterial vessel is formed by the union of two others - the vertebral arteries. It provides vascular supply to essential structures for the main vital functions; the posterior cerebral arteries originate from it as terminal branches, and form part of the anastomotic circle of Willis. IMAGING FINDINGS: Congenital and acquired anomalies of the basilar trunk are described. We provide a schematic and detailed representation of normal anatomical variants - mainly represented by the fenestrated basilar artery or the persistence of carotid-basilar anastomosis; course anomalies are also illustrated, with reference to neuro-vascular conflicts and dolichoectasia. Among congenital anomalies, this pictorial review also shows the variants of the basilar origin, such as in the case of basilar trunk arising from only one of the two vertebral arteries, and the calibre changes - which are represented by aneurysm and hypoplasia. The latter appears to be a risk factor for posterior circulation stroke, when associated with a bilateral posterior foetal variant.Among the acquired forms, this pictorial essay describes some clinical cases of dissections, non-congenital aneurysms, thrombosis and tumour with vascular encasing or compression of basilar artery. CONCLUSION: CT angiography and MRI allow us to study the posterior intracranial circulation in detail, providing useful pre-treatment information. Therefore, knowledge of congenital or acquired anomalies of the basilar artery is essential for radiologists, neuroradiologists and neurosurgeons.

Case report: A gain-of-function of hamartin may lead to a distinct "inverse TSC1-hamartin" phenotype characterized by reduced cell growth.

Mutations of TSC1 and TSC2 genes cause classical Tuberous Sclerosis Complex (TSC), a neurocutaneous disorder characterized by a tendency to develop hamartias, hamartomas, and other tumors. We herein report on a girl, now aged 5 years, who presented a previously unreported, distinct clinical phenotype consisting of primary microcephaly (head circumference = 40 cm, -5.6 standard deviations), brain anomalies including hypoplasia of the corpus callosum (with a residual draft of the genu), simplified parieto-temporal gyral pattern, colpocephaly with ectasia of the temporal ventricular horns, intellectual disability, and a general pattern of reduced growth (with weight and height < 3rd centiles). No classical features of TSC were recorded; the girl harbored a novel missense variant in TSC1 (c.611G > A). We hypothesize that her clinical phenotype could be related to a "gain-of-function" of the TSC1 protein product hamartin, causing an increase in the effects of the protein on inhibition of its intracellular targets (i.e., mTORC or RAC1 pathways), resulting in a distinct "inverse TSC1-hamartin" phenotype characterized by reduced growth of cells instead of the more classical predisposition to increased cell growth.

Case report: Incidence and prognostic value of brain MRI lesions and elevated cerebrospinal fluid protein in children with Guillain-Barré syndrome.

Background: Guillain-Barrè syndrome (GBS) is an acute immune-mediated disorder affecting peripheral nerves and nerve roots with a variable clinical course and outcome. Epidemiologic analyses have revealed that the incidence of the syndrome increases linearly among the age. The clinical diagnosis of GBS is based on the family history, physical and neurological examination, electrodiagnostic exams, and cerebrospinal fluid analysis with the classical presence of albumin-cytologic dissociation. Prognosis is associated with the severity of clinical signs and the type of peripheral nerves involved. Methods: This study aims to clarify which clinical features can be used for prognostic purposes. We evaluated the correlation between (1) brain MRI lesions and grade of disability; (2) brain MRI lesions and elevated cerebrospinal fluid (CSF) protein; and (3) increased levels of CSF protein and grade of disability. Statistical analysis extracted from these data indicated a good correlation to be a prognostic indicator in children affected by GBS. We found little evidence regarding laboratory tests, imaging, and prognosis. We enrolled 12 continuous patients who met the Brighton criteria for GBS in this retrospective study. Each patient was clinically evaluated at the time of disease onset to assess the GBS disability score and after 2 weeks. Results: We estimated Pearson's correlation index to evaluate the possible correlation between MRI and disability and CSF protein levels and disability. The correlation coefficient was 0.92 and 0.85, respectively. In addition, we developed a graph to see the trend of the disability values, proteins in the CSF, and damage assessed with MRI in the 12 patients. It seems that these parameters have a parallel trend and a good correlation in each patient. Finally, we calculated the correlation between MRI and CSF protein values, with an r-value of 0.87. The values suggest a correlation among the MRI score, CSF protein, and prognosis. Conclusion: The MRI and CSF laboratory parameters can be important tools for the clinician not only for diagnosis but also to evaluate the possible worsening of general conditions or the need to prepare measures to support life parameters. Patients who need ventilatory support could be established early from patients who have less severe GBS and can begin rehabilitation earlier. We suggest MRI should be performed routinely in children with GBS to be able to estimate the evolution of the clinical condition.

Report of Two Cases of Pediatric IgG4-Related Lymphadenopathy (IgG4-LAD): IgG4-Related Disease (IgG4-RD) or a Distinct Clinical Pathological Entity?

IgG4-related disease (IgG4-RD) is a recently discovered immune-mediated fibroinflammatory condition, uncommon in the pediatric population, that could involve multiple organs and induce cancer-like lesions and organ damage. Its main features are multiple injuries in different sites, a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells, storiform fibrosis, and often high serological concentrations of IgG4. Autoimmune pancreatitis is the most common manifestation, mainly in adults. Two cases of IgG4-RD in children with lymph node localization of disease are reported. Localized or systemic lymph node involvement is common, but lymph node enlargement as the first and only manifestation of IgG4-RD is unusual, and therefore, hard to differentiate from other diseases. IgG4-related lymphadenopathy (IgG4-LAD) is most likely a distinct disease, described as isolated lymphadenopathy, related to the presence of elevated numbers of IgG4-positive plasma cells. Both disorders are likely to be misdiagnosed in children because they are characterized by rare and polymorphic features. IgG4-RD and IgG4-LAD should be considered in the differential diagnosis of disorders characterized by lymphadenopathy of uncertain etiology.

An overview of the irreversible electroporation for the treatment of liver metastases: When to use it.

Tumour ablation is an established therapy for local treatment of liver metastases and hepatocellular carcinoma. Most commonly two different kind of thermic ablation, radiofrequency ablation and microwave ablation, are used in clinical practice. The aim of both is to induce thermic damage to the malignant cells in order to obtain coagulative necrosis of the neoplastic lesions. Our main concerns about these procedures are the collateral thermic damage to adjacent structures and heat-sink effect. Irreversible electroporation (IRE) is a recently developed, non-thermal ablation procedure which works applying short pulses of direct current that generate an electric field in the lesion area. The electric field increase the transmembrane potential, changing its permeability to ions.Irreversible electroporation does not generate heat, giving the chance to avoid the heat-sink effect and opening the path to a better treatment of all the lesions located in close proximity to big vessels and bile ducts. Electric fields produced by the IRE may affect endothelial cells and cholangiocytes but they spare the collagen matrix, preserving re-epithelization process as well as the function of the damaged structures. Purpose of the authors is to identify the different scenarios where CT-guided percutaneous IRE of the liver should be preferred to other ablative techniques and why.

Decreased Diversity and Abundance of Marine Invertebrates at CO2 Seeps in Warm-Temperate Japan.

Japan has many coastal carbon dioxide seeps as it is one of the most volcanically active parts of the world. These shallow seeps do not have the spectacular aggregations of specialist fauna seen in deep-sea vent systems but they do have gradients in seawater carbonate chemistry that are useful as natural analogues of the effects of ocean acidification on marine biodiversity, ecosystem function and fisheries. Here, we compare macroinvertebrate diversity and abundance on rocky habitats at ambient (mean ≤ 410 µatm) and high (mean 971-1484 µatm) levels of seawater pCO2 in the warm-temperate region of Japan, avoiding areas with toxic sulphur or warm-water conditions. We show that although 70% of intertidal taxa and 40% of shallow subtidal taxa were able to tolerate the high CO2 conditions, there was a marked reduction in the abundance of corals, bivalves and gastropods in acidified conditions. A narrower range of filter feeders, grazers, detritivores, scavengers and carnivores were present at high CO2 resulting in a simplified coastal system that was unable to retain the high standing stocks of marine carbon biomass found in ambient conditions. It is clear that cuts in CO2 emissions would reduce the risks of climate change and ocean acidification impacts on marine biodiversity, shellfish production and biomass in the rocky coastal shores of this region.

Spinal cord compression as tumor onset: an unusual case report of Hodgkin lymphoma in a teenager.

BACKGROUND: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us. CASE PRESENTATION: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function. CONCLUSIONS: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management.

Mandatory Reporting of Coronary Artery Calcifications Incidentally Noted on Chest Multi-Detector Computed Tomography: A Multicentre Experience.

BACKGROUND: Coronary Artery Calcifications (CACs) are associated with coronary atherosclerosis and Cardiovascular (CV) events. In "non-cardiovascular" settings, CACs can be easily detected on chest Multi-Detector Computed Tomography (MDCT). Their evaluation may help to better stratify CV risk in the general population, especially for primary prevention. AIMS: We retrospectively evaluated the relationship between CAC distribution and CV risk, determined by Framingham Risk Score (FRS), in a cohort of patients who underwent chest MDCT performed for several clinical indications. METHOD: We retrospectively recruited 305 patients (194 men, 111 women; mean age 70.5 years) from 3 different Italian centres. Patients with coronary stent, pacemaker and/or CV devices were excluded from the study. Circumflex Artery (LCX), Left Main Coronary Artery (LMCA), left Anterior Descending artery (LAD) and right coronary artery (RCA) were analysed. RESULTS: From a total population of 305 patients, 119 (39%) had low FRS (<10%), 115 (38%) had intermediate FRS (10-20%), and 71 (23%) had high FRS (>20%). The study identified 842 CACs located in decreasing order as follows: RCA (34.5%), LAD (32.3%), LCX (28%) and LMCA (13%). Statistical two-step analysis subdivided patients into two clusters according to FRS (risk threshold = 12.38%): cluster I (mean 9.34) and cluster II (mean 15.09). A significant association between CAC distribution and cluster II was demonstrated. CACs were mostly detected in patients with intermediate FRS. All patients (100%) with the highest CV risk showed intermediate RCA and LMCA involvement. CONCLUSION: Radiologists can note the distribution of CACs on a chest MDCT and should mandatorily record them in their reports. Depending on CAC presence and location, these findings may have important clinical implications, mostly in asymptomatic patients with intermediate FRS. This information may reclassify a patients' CV risk and improve clinical management.

Concurrent chemotherapy alone versus irreversible electroporation followed by chemotherapy on survival in patients with locally advanced pancreatic cancer.

Pancreatic adenocarcinoma is one of the most fatal cancers, characterized by aggressive tumor growth and a short patient survival time between diagnosis and death. Safe and effective treatment options are limited, especially in cases when surgical resection is not possible. Irreversible electroporation (IRE) is a non-thermal ablation technique recently introduced in the treatment of pancreatic cancer. From 2013 to 2016, 29 cases of locally advanced pancreatic cancer (LAPC) treated with IRE were retrospectively analyzed and the median overall survival (OS) rates were compared with patients with the same diagnosis who received standard chemotherapy as reported in the literature. Literature was selected according to a predetermined protocol. Secondarily, preoperative and postoperative Karnofsky scores of the 29 IRE-treated patients were compared to determine improvement in quality-of-life. Median OS of IRE-treated patients was 14 months (SE 11 months, 95% CI range 9.86-18.14). For IRE-treated patients, the Karnofsky score increased from Tzero to T3m by a mean of 28.28 (SE 2.11, 95% CI range 23.95-32.60). In 27 patients, 6-month imaging follow-up showed a mean lesion volumetric decrease percentage of 40.32% (SE 2.76, 95% CI 34.63-46.01%). Treatment with IRE followed by chemotherapy substantially increases median OS rate and quality-of-life of LAPC-diagnosed patients when compared to patients treated with traditional methods, including chemotherapy. Further investigation of this multi-modal treatment is warranted.

Mixed vascular nevus syndrome: a report of four new cases and a literature review.

BACKGROUND: Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as an purely cutaneous trait or as a hallmark of a neurocutaneous phenotype (mixed vascular nevus syndrome) characterised by the combination of: (I) paired vascular (telangiectatic and anemic) twin nevi and brain abnormalities of the Dyke-Davidoff-Masson type (i.e., crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels and homolateral hypertrophy of the skull and sinuses (hyperpneumatisation) with contralateral hemispheric hypertrophy); or (II) paired vascular twin nevi and brain malformations of the Dyke-Davidoff-Masson type in association with systemic abnormalities consisting in facial asymmetry, skeletal anomalies (i.e., Legg-Calvé-Perthes-like disease) and disorders of autoimmunity (i.e., diabetes, thyroiditis). In 2014, Happle proposed to name the syndrome with the eponym Ruggieri-Leech syndrome. METHODS: Review of the existing literature on nevus vascularis mixtus and information on our personal experience on new cases and follow-up of previously reported cases by some of us. RESULTS: The existing literature revealed 4 previous studies including 33 cases with an inferred purely cutaneous trait and 3 cases with a combination of paired vascular twin nevi and brain malformation of the Dyke-Davidoff-Masson type. Our personal experience includes 4 unpublished patients (1 female and 3 males; currently aged 2 to 34 years) seen and followed-up at our Institutions in Italy who had: paired vascular nevi involving either the face (n=2) or the face and parts of the body (n=2); facial asymmetry (n=4); mild to moderate facial dysmorphic features (n=2); developmental delay (n=3); seizures/stroke-like episodes and associated hemiplegia (n=4); muscular hypotrophy (n=2); mild to moderate hemispheric atrophy (n=4); skull osseous hypertrophy (n=4); hyperpneumatisation of the sinuses (n=2); hypoplastic brain vessels (n=4); colpocephaly and malformation of cortical development (n=2). Follow-up data on our previous 2 cases revealed that the vascular abnormalities in the skin and nervous system were stable over years without neurological progression or deterioration. CONCLUSIONS: Pathogenically, this complex phenotype suggests that embryonic pairing and somatic recombination of recessive (didymotic) alleles controlling the balance between constriction (i.e., nevus anemicus) and dilatation (i.e., nevus telangiectaticus) of blood vessels could be the primary event causing the phenomena of cutaneous and brain vascular twin spotting and the paired phenomena of skull hyperpneumatisation vs. hypertrophy and brain megalencephaly/colpocephaly vs. cortical dysplasia. This association is likely more frequent than previously thought and should be investigated by means of: (I) brain and spinal cord imaging (combination of CT and MRI studies); (II) skeletal X-ray studies (when dictated by clinical findings); (III) systemic ultrasound studies; (IV) neurophysiologic studies (EEG); (V) psychomotor testing; (VI) and laboratory investigation (including immune-mediated dysfunction).

Cutis tricolor: a literature review and report of five new cases.

BACKGROUND: Cutis tricolor is a skin abnormality consisting in a combination of congenital hyper- and hypopigmented skin lesions (in the form of paired macules, patches or streaks) in close proximity to each other in a background of normal skin. It is currently regarded as a twin-spotting (mosaic) phenomenon and today is clear that not all cases of cutis tricolor represent one single entity. This phenomenon has been reported so far either: (I) as an purely cutaneous trait; (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) including distinct facial features, eye (cataract), skeletal (skull and vertebral defects, and long bones dysplasia), nervous system (corpus callosum, cerebellar and white matter anomalies, cavum vergae and holoprosencephaly) and systemic abnormalities; (III) as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata); and (IV) in association with other skin disturbances [e.g., cutis marmorata telangectasica congenita (phacomatosis achromico-melano-marmorata)] or in the context of other skin (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis, PPV) or complex malformation phenotypes (e.g., microcephaly and dwarfism). METHODS: (I) Review of the existing literature; and (II) information on our personal experience (clinical, laboratory and imaging data) on new cases with cutis tricolor seen and followed-up at our institutions during years 2010-2016. RESULTS: The existing literature revealed 19 previous studies (35 cases) with pure cutaneous or syndromic cutis tricolor phenomena. Our personal experience included 5 unpublished patients (3 boys; 2 girls; currently aged 2 to 14 years) seen and followed-up at our Institutions in Italy who had: (I) skin manifestations of the cutis tricolor type (N=5); (II) skeletal abnormalities including small skull (n=2), obtuse angle of mandible (n=3), mild to moderate scoliosis (n=3), vertebral defects (n=3), and long bones bowing (n=3); mild psychomotor delay (n=3); epilepsy (n=2); anomalies of the corpus callosum (n=3); and cavum vergae (n =2). CONCLUSIONS: This study further confirms and expands the overall phenotype of cutis tricolor. By literature review and personal experience we conclude that the skin abnormalities of the cutis tricolor type are stable over time; the skeletal defects are mild to moderate and do not progress or cause relevant orthopaedic complications; the neurological/behavioural phenotype does not progress and the paroxysmal events (when present) tend to decrease over time; there is a typical facial phenotype in some patients (long, elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted nostrils), which characterizes a somewhat distinct syndromic phenotype; some patients may develop early onset cataracts. The allelic dydymotic hypothesis of post-zygotic mutations likely involving the same gene loci could well explain the overall skin, bone, lens and nervous system phenomena of migration of different streaks of clones in the different tissues.

Bilateral adrenal neuroblastoma in the infant: Is it an image-defined risk factor?

The treatment of neuroblastoma is based on the International Neuroblastoma Risk Group stratification considering life-threatening symptoms, image-defined risk factors (IDRFs), presence and site of metastases, biology, and histopathology. The authors present an infant with bilateral nonmetastatic adrenal neuroblastoma with favorable biology. Both tumors were resectable and without IDRFs, but bilateral resection was considered mutilating, so it was decided to operate one side only. The authors suggest considering bilaterality among IDRFs.

Preliminary Results in Unresectable Head and Neck Cancer Treated by Radiofrequency and Microwave Ablation: Feasibility, Efficacy, and Safety.

PURPOSE: To retrospectively determine whether the application of thermal ablation to recurrent and advanced head and neck cancer (HNC) could allow for local tumor control. MATERIALS AND METHODS: From 2002 to 2014, 22 patients (17 men and 5 women; mean age, 64 y; age range, 42-88 y) with unresectable HNC lesions treated with thermal ablation were evaluated. Patients were followed at 3 and 6 months after treatment, every 6 months for 5 years, and yearly thereafter with computed tomography and/or magnetic resonance imaging. The mean follow-up period was 32.2 months (range, 3-51 mo). RESULTS: Three of 22 patients with primary lesions are still alive; two of these patients were treated with radiofrequency (RF) ablation and one was treated with microwave (MW) ablation. Of the 19 remaining patients, four were treated with MW ablation and 15 were treated with RF ablation. Imaging revealed partial response in eight patients, and complete response was observed in the remaining 14. There were two major complications after ablation treatment. The mean survival time was 32.9 months ± 3.205 (standard error; 95% confidence interval [CI], 26.6-39.2 mo). The survival time for MW ablation cases (36 mo ± 5.185; 95% CI, 25.8-46.16 mo) was longer than for RF ablation (32.2 mo ± 3.911; 95% CI, 24.5-39.8 mo), although the CI overlap between the groups is large. CONCLUSIONS: Percutaneous thermal ablation is a promising alternative treatment for local control of incurable HNC.

Percutaneous CT-guided irreversible electroporation followed by chemotherapy as a novel neoadjuvant protocol in locally advanced pancreatic cancer: Our preliminary experience.

INTRODUCTION: Irreversible electroporation (IRE) is a non-thermal ablation technique recently used in pancreatic cancer. In our prospective study we evaluated safety, feasibility and efficacy of a neoadjuvant protocol based on CT-guided percutaneous IRE followed by chemotherapy in patients with locally advanced pancreatic cancer (LAPC). METHODS: We performed CT-guided percutaneous IRE in 20 patients with LAPC, followed by a combination of gemcitabine (1000 mg/mq) and oxaliplatin (100 mg/mq) biweekly. Imaging follow-up was performed by a contrast enhanced CT scan at 1, 3, 6 months and then every 3 months. RESULTS: No major complications occurred. Two patients died 3 and 4 months after IRE because of rapidly progressive disease. In the remaining 18 patients 6-month imaging follow-up showed a mean lesions volumetric decrease percentage of 42.89% (95% Confidence Interval: 34.90-54.88%). Thanks to lesions downstaging, three patients underwent R0 resection. At last available follow-up (mean follow-up 91 months; range 6-14), imaging showed no disease progression or post-surgical relapse in all 18 cases. The mean estimated survival was 12,950 months (95% CI: 11,570-14,332). CONCLUSIONS: Our preliminary study suggests that IRE followed by chemotherapy is safe, feasible and effective in producing local control of LAPC, with a possible downstaging effect to resectable lesions.

Long-term local disease control in a recurrent soft-tissue sarcoma of the thigh treated by radiofrequency ablation.

In 2008, we performed radiofrequency ablation (RFA) in an elderly patient with a large recurrent soft-tissue sarcoma of the thigh, previously treated with surgery and radiotherapy. After ablation, a marked shrinkage of tumor was obtained. Further local recurrences occurred during follow-up, all safely treated by RFA, with local control of the disease maintained until 6-year follow-up. RFA was safe, effective, and repeatable for soft-tissue sarcoma recurrences, and allowed long-term local control of the disease.

Imaging findings of mucopolysaccharidoses: a pictorial review.

INTRODUCTION: Mucopolysaccharidosis (MPS) represent a heterogeneous group of inheritable lysosomal storage diseases in which the accumulation of undegraded glycosaminoglycans (GAGs) leads to progressive damage of affected tissues. The typical symptoms include organomegaly, dysostosis multiplex, mental retardation and developmental delay. Definitive diagnosis is usually possible through enzymatic assays of the defective enzyme in cultured fibroblasts or leukocytes. IMAGING FINDINGS: Radiological and neuroradiological findings are reported. The most important neuroradiological features include abnormal signal intensity in the white matter, dilatation of periventricular spaces, widening of cortical sulci, brain atrophy, enlargement of extraventricular spaces and spinal cord compression. With reference to the skeletal system, most important radiological findings include multiplex dysostosis, which is represented by several bone malformations found in the skull, hands, legs, arms and column. The abnormal storage of GAGs leads to liver and spleen enlargement; it also damages cartilage layers and synovial recesses in the joints. CONCLUSION: The aim of this pictorial essay is to describe the imaging findings of MPS, represented by skeletal and neurological features; skeletal X-ray and MR allow an assessment of the severity of disease, to plan medical and surgical therapy and to evaluate response to treatment. TEACHING POINTS: • To describe the imaging findings common to different types of MPS. • To describe multiplex dysostosis encountered in the axial and appendicular skeleton. • To evaluate neuroradiological features of MPS, including brain abnormal signal intensity and atrophy. • To evaluate important otorhinolaryngological problems, such as otitis media and airways obstruction.

Natural history of neurofibromatosis type 2 with onset before the age of 1 year.

Neurofibromatosis type 2 (NF2) with onset before the first year of life has been anecdotally reported in the literature. We (a) prospectively (years 1997-2012) followed up three unrelated NF2 children, all harbouring NF2 gene mutations whose onset of disease was before age 1 year, and (b) systematically reviewed published reports on NF2 in the youngest age group (i.e. onset <1 year). The present three children had (1) small (<1 cm), bilateral vestibular schwannomas (VSs) detected (as an incidental finding) at magnetic resonance imaging (MRI) by the age of 4 to 5 months that were asymptomatic for 10 to 14 years, with sudden and rapid (<12 months) progression in two cases at the age of 11 and 15 years, respectively; (2) development of large numbers of skin NF2 plaques mainly in atypical locations (i.e. face, hands, legs and knees), which reverted to normal skin appearance at the time of VSs progression; (3) lens opacities (n = 1) and NF2 retinal changes (n = 2) detected as early as age of 3-4 months; (4) diffuse (asymptomatic) high signal lesions at brain MRI in the periventricular regions (alike cortical dysplasia); and (5) unaffected first-degree relatives who did not harbour NF2 gene abnormalities. This represents the youngest NF2 group with the longest prospective follow-up so far reported. NF2 may present as a congenital form with bilateral VSs presenting as early as the first months of life and with natural history different to that which occurs in classical NF2.