Abstract Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant inherited disorder characterized by selective weakness of face and upper arms and girdle. Respiratory involvement in ...FSHD has been described mainly in the most severely affected patients. In this work we tested the respiratory function by spirometry in 12 patients affected by FSHD with onset before 18 years. Spirometry results were correlated with motor involvement and compared to aged matched group of Becker patients. Of note FSHD patients present a peculiar pattern characterized by a flat shape in flow-volume loop. Respiratory volumes correlate with clinical severity and expiratory phase is specifically affected in comparison to other muscular dystrophies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gaucher disease (GD) type 1 is the most common lysosomal storage disorder due to beta glucocerebrosidase deficiency leading to an abnormal accumulation of its substrate, glucocerebroside, in the ...mononuclear phagocyte system. The disease presentation is usually characterized by signs and symptoms related to hypersplenism, such as splenomegaly, anaemia, thrombocytopenia and leucopenia. Skeletal disease may occur later for the infiltration of bone marrow by macrophages infiltration and bone resorption: bone involvement may be heterogeneously manifested by symptoms ranging from bone crisis to avascular necrosis, osteoporosis and defect in remodeling of long bones. Herein, we report a patient in whom the osteoarticular involvement has been the only symptom of the disease stressing that this unusual presentation of GD has prompted a wide differential diagnosis with more common forms of coxitis.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Allopurinol-induced drug reaction syndrome with eosinophilia and systemic symptoms (A-DRESS) is a well-described condition in adults, whereas it is uncommon among children. We describe a case of ...A-DRESS in a 16-year-old male with steroid-dependent nephrotic syndrome. He presented a life-threatening clinical course with persisting fever, skin rash, eosinophilia, lymphadenopathy, distributive shock, and herpesvirus 6 detection. The withdrawal of allopurinol and a combination of intravenous immunoglobulins (IVIGs) and systemic corticosteroids led to the patient's recovery without sequelae. Drug reaction with eosinophilia and systemic symptoms (DRESS) in pediatrics is rare and can present in a severe form. Early diagnosis and timely treatment are critical for prognostic purposes. This report suggests the potentially crucial role of IVIG in the treatment of patients with A-DRESS.
Mitochondrial disorders are a heterogeneous group of diseases sharing a defect of the oxidative phosphorylation system. Point mutations in the mitochondrial DNA are a common cause of mitochondrial ...disorders and frequently affect the sequences encoding mitochondrial transfer RNAs. The m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) is traditionally reported in patients with clinical features of the mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and in mitochondrial diabetes. Here we describe the clinical, pathological, and molecular features of an Italian child and his asymptomatic mother, carrying the m.3271T>C mutation in the mitochondrial tRNA(Leu(UUR)) gene, in association with an unusual clinical phenotype dominated by hypertrophic cardiomyopathy and provide review literature of cases with this mutation. To the best of our knowledge, there are no reports describing the association of this mutation with cardiomyopathy, and our cases suggest that the m.3271T>C mutation has to be taken into account in the diagnostic approach of maternally inherited cardiomyopathies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ObjectivesFacioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers (≤8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an ...infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1–3 repeats (1–3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1–3 DRA.SettingItaly.Participants66 index cases and 33 relatives carrying 1–3 DRA.OutcomesThe clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk.ResultsNo patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1–3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment.ConclusionsThe size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity.
Background: Pneumocytis jirovecii pneumonia (PJP) has high mortality rates in immunocompromised children, even though routine prophylaxis has decreased in incidence. The aim of this case series is to ...present the radiological and clinical pathway of PJP in a pediatric population. Description of Cases: All PJP cases in non-HIV/AIDS patients diagnosed at Istituto Giannina Gaslini Pediatric Hospital in Genoa (Italy) from January 2012 until October 2022 were retrospectively evaluated. Nine cases were identified (median age: 8.3 years), and of these, 6/9 underwent prophylaxis with trimethoprim/sulfamethoxazole (TMP/SMX; five once-a-week schedules and one three times-a-week schedule), while 3/9 did not receive this. PJP was diagnosed by real-time PCR for P. jirovecii-DNA in respiratory specimens in 7/9 cases and two consecutive positive detections of β-d-glucan (BDG) in the serum in 2/9 cases. Most patients (6/8) had a CT scan with features suggestive of PJP, while one patient did not undergo a scan. All patients were treated with TMP/SMX after a median time from symptoms onset of 3 days. In 7/9 cases, empirical TMP/SMX treatment was initiated after clinical suspicion and radiological evidence and later confirmed by microbiological data. Clinical improvement with the resolution of respiratory failure and 30-day survival included 100% of the study population. Discussion: Due to the difficulty in obtaining biopsy specimens, PJP diagnosis is usually considered probable in most cases. Moreover, the severity of the clinical presentation often leads physicians to start TMP/SMX treatment empirically. BDG proved to be a useful tool for diagnosis, and CT showed good accuracy in identifying typical patterns. In our center, single-day/week prophylaxis was ineffective in high-risk patients; the three-day/week schedule would, therefore, seem preferable and, in any case, should be started promptly in all patients who have an indication of pneumonia.
Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases ...still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs:
MTM1, DNM2, RYR1
and
BIN1
. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in
MTM1
, 6 in
DNM2
, 3 in
RYR1
and one in
TTN
. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in
DNM2
. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in
DNM2
, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
Autoinflammatory diseases are a group monogenic inflammatory conditions characterized by an early onset during childhood.
Discussion
Under the term “periodic fevers” are gathered some ...monogenic diseases (familial Mediterranean fever, mevalonate kinase deficiency, and tumor necrosis factor receptor-associated syndrome) characterized by periodic or recurrent episodes of systemic inflammation causing fever often associated with rash, serositis (peritonitis, pleuritis), lymphadenopathy, arthritis, and other clinical manifestations. Systemic reactive (AA) amyloidosis may be a severe long-term complication. Cryopyrinopathies are a group of conditions associated to mutations of the gene
Cryopyrin
that are responsible for a spectrum of diseases (familial cold autoinflammatory syndrome, Muckle–Wells syndrome, and chronic infantile neurological cutaneous and articular syndrome) characterized by a chronic or recurrent systemic inflammation variably associated with a number of clinical features, such as urticarial-like rash, arthritis, sensorineural deafness, and central nervous system and bone involvement. Other disorders are dominated by the presence of sterile pyogen abscesses prevalently affecting the skin, joints, and bones (pyogenic disorders). These include pyogenic sterile arthritis, pyoderma gangrenosum, and acne syndrome, and Majeed syndrome. Finally, some diseases, such as Blau’s syndrome, are characterized by the appearance of typical noncaseating granulomatous inflammation affecting the joints, skin, and uveal tract (granulomatous disorders). In the present review, we will focus on the clinical presentation of these disorders in childhood and report on the available therapeutic strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Below-average reading performances have been reported in individuals with Duchenne muscular dystrophy (DMD), but literacy problems in these subjects have yet to be characterized. In this study, the ...presence and characteristics of literacy deficits in boys with DMD were investigated through a comparison with typically developing children and with children affected by developmental dyslexia, with the aim of clarifying whether DMD and developmental dyslexia have overlapping profiles of literacy deficits and whether these deficits are associated, as in children with dyslexia, with impairments in phonological processing and rapid lexical access.
The results confirmed the high incidence of literacy problems in boys with DMD and revealed a profile less severe than, but qualitatively similar to, that of Italian children with developmental dyslexia. Both groups showed specific difficulties in reading and writing words and a reduced rapid automatized naming (RAN) speed. This is the first time that a RAN speed deficit has been documented in DMD. Moreover, the boys with DMD and the subgroup of dyslexic children with a previous language delay showed additional deficits in phonological processing.
The impairments highlighted in this study could explain the reading difficulties observed in boys with DMD and suggest that there is a need for targeted preschool interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
► Neutral lipid storage disease with myopathy (NLSDM) is associated with mutations in the PNPLA2 gene. ► Muscle symptoms usually start at the beginning of the third decade of life. ► In a 14-year-old ...boy with asymptomatic hyperCKemia two heterozygous mutations in the PNPLA2 gene were identified. ► A lipid storage myopathy should be considered in children with hyperCKemia.
We report a 14-year-old-boy with markedly elevated serum creatine kinase (CK) levels, in whom massive triglyceride storage was found in peripheral blood leukocytes and in muscle biopsy. Sequencing PNPLA2, the gene encoding the adipose triglyceride lipase (ATGL) and responsible for the neutral lipid storage disease with myopathy (NLSDM), we identified two heterozygous mutations, including a previously reported nonsense and a novel missense mutation in the patatin domain of the gene.
Lipid storage myopathy can be clinically silent in childhood and presenting only with hyperCKemia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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