Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

Background and purpose Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided. Results Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. Conclusions NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels

Visual Loss in Orbitofacial Neurofibromatosis Type 1

Geneeskunde en GesondheidswetenskappeOogheelkundePlease help us populate SUNScholar with the post print version of this article. It can be e-mailed to: [email protected]

Rare neonatal diabetes insipidus and associated late risks: Case report

<p>Abstract</p> <p>Background</p> <p>Most cases of neonatal central diabetes insipidus are caused by an injury, which often results in other handicaps in the patient. The infant’s prognosis will be determined by his or her own early age and disability as well as by the physician’s skill. However, the rarity of this condition prevents the acquisition of personal experience dealing with it.</p> <p>Case Presentation</p> <p> A neonatal hemorrhagic stroke, caused by an aortic coarctation, caused right lower limb paresis, swallowing disability, and central diabetes insipidus in a term infant. The scant oral intake, as a consequence of his disability, caused progressive undernutrition which closed a vicious circle, delaying his development and his ability to overcome the swallowing handicap. On the other hand, nasal desmopressin absorption was blocked by several common colds, resulting in brain bleeding because of severe dehydration. This even greater brain damage hampered the improvement of swallowing, closing a second harmful circle. Moreover, a devastating central myelinolysis with quadriplegia, caused by an uncontrolled intravenous infusion, consummated a pernicious sequence, possibly unreported.</p> <p>Conclusions</p> <p>The child’s overall development advanced rapidly when his nutrition was improved by gastrostomy: This was a key effect of nutrition on his highly sensitive neurodevelopment. Besides, this case shows potential risks related to intranasal desmopressin treatment in young children.</p