Hereditary angioedema with normal C1-inhibitor: Clinical and genetic characterization of 15 Portuguese unrelated families.

Background: Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease with similar phenotype to HAE-C1-INH but different genetic background. Currently, 6 subtypes are recognized, based on the underlying mutations. Several aspects need further clarification.

Lissencephaly With Cerebellar Hypoplasia Due To a New RELN Mutation.

Lissencephaly with cerebellar hypoplasia (LCH) is a rare variant form of lissencephaly, its distinctive neuroradiological phenotype being an important investigation clue regarding the potential involved genes, including variants in RELN gene. We report on a case of LCH whose clinical and neuroradiological features led to the identification of a homozygous pathogenic variant in RELN gene that has not been previously reported in the scientific literature.

TANGO2 Deficiency Disorder: Two Cases of Developmental Delay Preceding Metabolic Crisis.

Background: TANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene.

Methods: We report the clinical phenotype of two children with TANGO2 deficiency disorder.

Results: Patient 1 is a female child presenting with developmental delay and microcephaly during the second year of life, who evolved with severe cognitive impairment, facial dysmorphisms, spastic paraparesis, and atonic seizures.

Case Report: Patient with deficiency of ADA2 presenting leukocytoclastic vasculitis and pericarditis during infliximab treatment.

Deficiency of adenosine deaminase 2 (DADA2), first reported in 2014, is a disease with great phenotypic variability, which has been increasingly reported. Therapeutic response depends on the phenotype. We present a case of an adolescent with recurrent fever, oral aphthous ulcers, and lymphadenopathy from 8 to 12 years of age and subsequently presented with symptomatic neutropenia.

Aberrant Splicing Caused by a Novel VPS16 Variant Linked to Dystonia Type 30.

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent involuntary muscle contractions, causing abnormal postures and/or repetitive movements. In this report, we identified a novel heterozygous splice-site variant in VPS16 (NM_022575.4:c.

Diagnosis across a cohort of "atypical" atypical and complex parkinsonism.

Introduction: The diagnostic approach for adulthood parkinsonism can be challenging when atypical features hamper its classification in one of the two main parkinsonian groups: Parkinson's disease or atypical parkinsonian syndromes (APS). Atypical features are usually associated with non-sporadic neurodegenerative causes.

Methods: Retrospective analysis of patients with a working clinical diagnosis of "atypical" APS and complex parkinsonism.

Clinical Role of Codon 87 of the CYFIP2 Gene in Early Infantile Epileptic Encephalopathy: A Clinical Case Description.

The diagnosis of early infantile epileptic encephalopathy (EIEE) remains challenging, and next-generation sequencing (NGS) techniques have played a key role in identifying genetic causes. Recent studies have shown an association between mutations in the  gene and EIEE, with 20 deleterious variants reported so far and a  mutational hotspot at codon 87.  A male infant presented with seizures since the age of four months as well as significant developmental delay and microcephaly.

Case Report: Wide Spectrum of Manifestations of Ligase IV Deficiency: Report of 3 Cases.

DNA ligase IV deficiency is a rare autosomal recessive disorder associated with impaired DNA repair mechanisms. Most patients with DNA repair defects present with neurologic deficits, combined immunodeficiency, bone marrow failure, and/or hematologic neoplasia. We present 3 unrelated cases of ligase IV deficiency with different clinical presentations.

Congenital heart defects associated with pathogenic variants in WAC gene: Expanding the phenotypic and genotypic spectrum of DeSanto-Shinawi syndrome.

WAC-related intellectual disability, also known as DeSanto-Shinawi syndrome, is a rare autosomal dominant genetic disorder caused by pathogenic variants in WAC gene. This syndrome is characterized by developmental delay, intellectual disability, behavioral abnormalities, and dysmorphic facial features, including deep-set eyes, flat nasal bridge, bulbous nasal tip, and synophrys. Chromosomal deletions at 10p12p11 encompassing WAC gene have been described in patients with a similar phenotype, presenting with developmental delay, intellectual disability, visual impairments, abnormal behavior, and dysmorphic features.

Parkinsonism and iron deposition in two adult patients with L-2-hydroxiglutaric aciduria.

L-2-hydroxiglutaric aciduria (L2HGA) is a rare, childhood-onset, organic aciduria, with characteristic clinical (cerebellar ataxia) and neuroimaging (subcortical leukodystrophy) features. Movement disorders in this condition are usually of hyperkinetic type. Herein is reported the case of two adult siblings with recent L2HGA diagnosis, presenting with dopa-responsive parkinsonism and MRI iron deposition.

Spasmodic cough preceding CANVAS phenotype in a family with biallelic repeat expansions in RFC1.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset, multisystem ataxia that remained only clinically defined, until recently, when the discovery of biallelic repeat expansion in the RFC1 gene allowed the genetic link. We describe the first Portuguese familial CANVAS harboring the pathogenic RFC1 expansion. Detail clinical features and course of four affected members are provided.

X-linked hypophosphatemic rickets: a new mutation.

Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs.