Variable Presentation and Reduced Penetrance in Autosomal Dominant Acute Necrotizing Encephalopathy Related to RANBP2 Variant.

Acute necrotizing encephalopathy (ANE) is clinically characterized by fever, acute alteration of consciousness, seizures, and rapid progression to coma within days of onset of a viral illness occurring in healthy children without evidence of central nervous system infection. Brain magnetic resonance imaging (MRI) shows multiple symmetrical lesions affecting primarily the thalami but also brain stem, putamina, periventricular white matter, and cerebellum. Most cases of ANE are sporadic and nonrecurrent.

Spondyloepimetaphyseal dysplasia with elevated plasma lysosomal enzymes caused by homozygous variant in MBTPS1.

Variants in MBTPS1 (membrane-bound transcription factor peptidase, site 1) encoding the protein convertase site-1 protease (S1P) were recently reported in a single individual with skeletal dysplasia and elevated plasma lysosomal enzymes. Here, we report the second individual with this newly described autosomal recessive spondyloepiphyseal dysplasia (OMIM #618392), presenting severe growth retardation, cataract and dysmorphic features, mainly retromicrognathia. Epilepsy and craniosynostosis were novel findings in our proband.

Modelling the pathogenesis of X-linked distal hereditary motor neuropathy using patient-derived iPSCs.

encodes a copper-transporting P-type ATPase and is one of 23 genes in which mutations produce distal hereditary motor neuropathy (dHMN), a group of diseases characterized by length-dependent axonal degeneration of motor neurons. We have generated induced pluripotent stem cell (iPSC)-derived motor neurons from a patient with the p.T994I gene mutation as an model for X-linked dHMN (dHMNX).

19q13.11 microdeletion: Clinical features overlapping ectrodactyly ectodermal dysplasia-clefting syndrome phenotype.

We report a patient who was followed for a long time under an ectrodactyly ectodermal dysplasia-clefting (EEC) syndrome and was subsequently diagnosed with a 19q13.11 microdeletion. After a review of the related literature, we suggest testing patients with EEC for 19q13.

Analysis of mutations in EXT1 and EXT2 in Brazilian patients with multiple osteochondromas.

Background: Multiple osteochondromas is a dysplasia characterized by growth of two or more osteochondromas. It is genetically heterogeneous, caused by pathogenic variants in EXT1 or EXT2 genes in 70%-90% of patients. The EXT1 is more often mutated than EXT2 gene, with a variable prevalence between populations.

Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome.

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH).

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome.

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function.

Characterizing the molecular phenotype of an Atp7a(T985I) conditional knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX).

ATP7A is a P-type ATPase essential for cellular copper (Cu) transport and homeostasis. Loss-of-function ATP7A mutations causing systemic Cu deficiency are associated with severe Menkes disease or its milder allelic variant, occipital horn syndrome. We previously identified two rare ATP7A missense mutations (P1386S and T994I) leading to a non-fatal form of motor neuron disorder, X-linked distal hereditary motor neuropathy (dHMNX), without overt signs of systemic Cu deficiency.

Analysis of novel ARG1 mutations causing hyperargininemia and correlation with arginase I activity in erythrocytes.

Hyperargininemia (HA) is an autosomal recessive disease that typically has a clinical presentation that is distinct from other urea cycle disorders. It is caused by the deficient activity of the enzyme arginase I, encoded by the gene ARG1. We screened for ARG1 mutations and measured erythrocyte enzyme activity in a series of 16 Brazilian HA patients.

Brain MRI and magnetic resonance spectroscopy findings in patients with hyperargininemia.

Background And Purpose: Hyperargininemia (HA) is a rare autosomal recessive metabolic disorder and the neuroimaging features of this disease have seldom been reported. Hyperammonemic encephalopathy is uncommon in HA, and the clinical presentation of HA is distinct from other urea cycle disorders. This paper describes the brain MRI findings and a magnetic resonance spectroscopy (MRS) study of a series of Brazilian HA patients.

Severe neurologic manifestations from cervical spine instability in spondylo-megaepiphyseal-metaphyseal dysplasia.

Spondylo-megaepiphyseal-metaphyseal dysplasia (SMMD; OMIM 613330) is a dysostosis/dysplasia caused by recessive mutations in the homeobox-containing gene, NKX3-2 (formerly known as BAPX1). Because of the rarity of the condition, its diagnostic features and natural course are not well known. We describe clinical and radiographic findings in six patients (five of which with homozygous mutations in the NKX3-2 gene) and highlight the unusual and severe changes in the cervical spine and the neurologic complications.

Clinical features and neurologic progression of hyperargininemia.

Hyperargininemia is an autosomal recessive metabolic disorder caused by a deficiency of enzyme arginase I. It is a rare pan-ethnic disease with a clinical presentation distinct from that of other urea cycle disorders, and hyperammonemic encephalopathy is not usually observed. Hyperargininemia is one of the few treatable causes of pediatric spastic paraparesis, and can be confused with cerebral palsy.

Tibial hemimelia in Langer-Giedion syndrome with 8q23.1-q24.12 interstitial deletion.

Langer-Giedion syndrome (LGS) (OMIM 150230) is defined as a contiguous gene syndrome caused by loss of functional copies of the TRPS1 and EXT1 genes usually secondary to 8q microdeletion. Tibial hemimelia (TH) is the least common lower limb deficiency characterized by hypoplasia of the tibia with relatively intact fibula. We describe the third report of LGS with bilateral TH and an 8q23.

Additional features of unique Primrose syndrome phenotype.

Primrose syndrome is a unique condition of intellectual disability, dysmorphic facial features, and specific minor abnormalities including large calcified ear auricles. Only six patients have been previously reported. We describe a Brazilian boy with the striking similar facies and the main clinical findings that reinforced the singular phenotype of this rare disorder.

Craniofacial findings in fibrodysplasia ossificans progressiva: computerized tomography evaluation.

Objective: The aim of this study was the evaluation by using computerized tomography (CT) of craniofacial abnormalities in fibrodysplasia ossificans progressiva (FOP) patients regarding jaw restriction and retrognathia.

Study Design: Seven FOP patients were evaluated retrospectively in this observational study. Inclusion criteria were detection of ACVR1 gene mutation and complete craniofacial CT examination.

Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy.

Distal hereditary motor neuropathies comprise a clinically and genetically heterogeneous group of disorders. We recently mapped an X-linked form of this condition to chromosome Xq13.1-q21 in two large unrelated families.

Apolipoprotein E genotype and cerebral palsy.

Aim: Apolipoprotein E (APOE, protein; [ApoE, gene]) is a lipid transport protein abundantly present in brain cells. We investigated whether the APOE genotype is associated with cerebral palsy (CP) and whether patients with CP with comorbid conditions and more severe neurological deficits are likely to have a particular genotype.

Method: In a cross-sectional study, 243 individuals with spastic CP (135 males, 108 females; mean age at data collection 11 year ([SD 6y 7mo], 34% with hemiplegia, 37% with diplegia, 29% with triplegia/tetraplegia; 44% with mild motor involvement), 31% with moderate motor involvement, 25% with severe motor involvement, were compared with healthy individuals matched by age, race, and sex to analyse the association between APOE genotype and the incidence of CP.