Expanding the Phenotypic Spectrum of TRAF7-Related Cardiac, Facial, and Digital Anomalies With Developmental Delay: Report of 11 New Cases and Literature Review.

Background: TRAF7-related cardiac, facial, and digital anomalies with developmental delay (CAFDADD), a multisystemic neurodevelopmental disorder caused by germline missense variants in the TRAF7 gene, exhibits heterogeneous clinical presentations.

Methods: We present a detailed description of 11 new TRAF7-related CAFDADD cases, featuring eight distinct variants, including a novel one.

Results: Phenotypic analysis and a comprehensive review of the 58 previously reported cases outline consistent clinical presentations, emphasizing dysmorphic features, developmental delay, endocrine manifestations, and cardiac defects.

Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies.

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20.

Beyond the known phenotype of sotos syndrome: a 31-individuals cohort study.

Introduction: Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly, typical facial appearance and different degrees of intellectual disability. Three different types are described caused by variants or deletions/duplications in and genes. We aimed to describe a cohort of pediatric patients reporting the typical and unexpected findings in order to expand the phenotype of this syndrome and trying to find genotype-phenotype correlations.

Targeting the Gut Microbiome in Prader-Willi Syndrome.

Overwhelming evidence demonstrates an important role of the gut microbiome in the development of a wide range of diseases, including obesity, metabolic disorders, and mental health symptoms. Indeed, interventions targeting the gut microbiome are being actively investigated as a therapeutic strategy to tackle these diseases. Given that obesity and mental health symptoms are both hallmarks of Prader-Willi syndrome, targeting the gut microbiome may be a promising therapeutical strategy.

-Related Disorders in Males.

Methyl CpG binding protein 2 () is located at Xq28 and is a multifunctional gene with ubiquitous expression. Loss-of-function mutations in are associated with Rett syndrome (RTT), which is a well-characterized disorder that affects mainly females. In boys, however, mutations in can generate a wide spectrum of clinical presentations that range from mild intellectual impairment to severe neonatal encephalopathy and premature death.

Mutations Causing Early Onset Ataxia: Profiling Clinical, Dysmorphic and Structural-Functional Findings.

The gene encodes the pore-forming α subunit of the voltage-gated Ca2.1 Ca channel, essential in neurotransmission, especially in Purkinje cells. Mutations in result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both.

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND): Case report, pharmacological trial, and literature review.

Early-onset severe spinocerebellar ataxia 42 with neurodevelopmental deficits (SCA42ND, MIM#604065) is an ultrarare autosomal dominant syndrome related to de novo CACNA1G gain-of-function pathogenic variants. All patients with SCA42ND show cerebellar atrophy and/or hypoplasia on neuroimaging and share common features such as dysmorphic features, global developmental delay, and axial hypotonia, all manifesting within the first year of life. To date, only 10 patients with SCA42ND have been reported with functionally confirmed gain-of-function variants, bearing either of two recurrent pathogenic variants.

Platelet Dysfunction in Noonan and 22q11.2 Deletion Syndromes in Childhood.

Introduction:  An underlying thrombocytopathy seems to be responsible for hemorrhagic symptoms in patients diagnosed with 22q11.2 deletion syndrome (22q11DS) or Noonan syndrome (NS). In 22q11DS, it is explained by a defect in the membrane glycoprotein (GP) complex Ib-V-IX.

Molecular characterization of Spanish patients with MECP2 duplication syndrome.

MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder characterized by a severe to profound intellectual disability, early onset hypotonia and diverse psycho-motor and behavioural features. To date, fewer than 200 cases have been published. We report the clinical and molecular characterization of a Spanish MDS cohort that included 19 boys and 2 girls.

Okur-Chung neurodevelopmental syndrome in a patient from Spain.

Okur-Chung neurodevelopmental syndrome (OCNS, MIM#617062) is a rare autosomal dominant syndrome related to CSNK2A1 mutations. It is characterized by intellectual disability, hypotonia, feeding and speech difficulties, dysmorphic features, and multisystem involvement. To date, less than 30 patients with OCNS have been described in detail in the literature, primarily in Asian populations.

AZATAX: Acetazolamide safety and efficacy in cerebellar syndrome in PMM2 congenital disorder of glycosylation (PMM2-CDG).

Objective: Phosphomannomutase deficiency (PMM2 congenital disorder of glycosylation [PMM2-CDG]) causes cerebellar syndrome and strokelike episodes (SLEs). SLEs are also described in patients with gain-of-function mutations in the CaV2.1 channel, for which acetazolamide therapy is suggested.

Clinical Assessment of Dysarthria in Children with Cerebellar Syndrome Associated with PMM2-CDG.

Phosphomannomutase deficiency (PMM2-CDG) causes a cerebellar syndrome that has been evaluated using the International Cooperative Ataxia Rating Scale (ICARS). However, no particular dysarthria tests have been used. Speech ICARS subscore subjectively assesses fluency and clarity of speech with two items.

Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy.

Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in (encoding Ca2.1 channel). The underlying pathomechanisms are unknown.

A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG).

Background: We aim to delineate the progression of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG) using the International Cooperative Ataxia Rating Scale (ICARS). We sought correlation between cerebellar volumetry and clinical situation. We prospectively evaluated PMM2-CDG patients aged from 5 to 18 years through ICARS at two different time points set apart by at least 20 months.

Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG).

Objective: We aim to delineate the progression of cerebellar atrophy (the primary neuroimaging finding) in children with phosphomannomutase-deficiency (PMM2-CDG) by analyzing longitudinal MRI studies and performing cerebellar volumetric analysis and a 2D cerebellar measurement.

Methods: Statistical analysis was used to compare MRI measurements [midsagittal vermis relative diameter (MVRD) and volume] of children with PMM2-CDG and sex- and age-matched controls, and to determine the rate of progression of cerebellar atrophy at different ages.

Results: Fifty MRI studies of 33 PMM2-CDG patients were used for 2D evaluation, and 19 MRI studies were available for volumetric analysis.

Changes in Parenteral Nutrition During the First Week of Life Influence Early but Not Late Postnatal Growth in Very Low-Birth-Weight Infants.

Background And Aims: Postnatal growth restriction remains a serious problem in very low-birth-weight infants. Enhanced parenteral supply of nutrients as soon as possible after birth is one of the strategies addressed to avoid extrauterine growth restriction. We aimed to analyze changes in growth patterns and in clinical outcomes in our unit after a change in our parenteral nutrition (PN) protocol.