Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 37-year-old housewife, who had physical characteristics of cerebral gigantism, such as the tall stature, acromegaly, macrocephalia, high arched palate and antimongoloid slant, developed cerebellar ataxia and dysarthria. Her mother, uncle and grandmother were also reported to have slowly progressive gait disturbance. Her mother was also tall. Endocrinological studies failed to show any definite abnormality. CT and MRI revealed remarkable cerebellar atrophy. Though cerebral gigantism is often associated with clumsiness and incoordination, the etiology of the ataxia is poorly understood. This case indicates that the ataxia in cerebral gigantism may be, at least partly, caused by cerebellar atrophy.
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PMID:[A case of cerebral gigantism with cerebellar atrophy]. 240 Nov 12

De novo monoallelic variants in NFIX cause two distinct syndromes. Whole gene deletions, nonsense variants and missense variants affecting the DNA-binding domain have been seen in association with a Sotos-like phenotype that we propose is referred to as Malan syndrome. Frameshift and splice-site variants thought to avoid nonsense-mediated RNA decay have been seen in Marshall-Smith syndrome. We report six additional patients with Malan syndrome and de novo NFIX deletions or sequence variants and review the 20 patients now reported. The phenotype is characterised by moderate postnatal overgrowth and macrocephaly. Median height and head circumference in childhood are 2.0 and 2.3 standard deviations (SD) above the mean, respectively. There is overlap of the facial phenotype with NSD1-positive Sotos syndrome in some cases including a prominent forehead, high anterior hairline, downslanting palpebral fissures and prominent chin. Neonatal feeding difficulties and/or hypotonia have been reported in 30% of patients. Developmental delay/learning disability have been reported in all cases and are typically moderate. Ocular phenotypes are common, including strabismus (65%), nystagmus (25% ) and optic disc pallor/hypoplasia (25%). Other recurrent features include pectus excavatum (40%) and scoliosis (25%). Eight reported patients have a deletion also encompassing CACNA1A, haploinsufficiency of which causes episodic ataxia type 2 or familial hemiplegic migraine. One previous case had episodic ataxia and one case we report has had cyclical vomiting responsive to pizotifen. In individuals with this contiguous gene deletion syndrome, awareness of possible later neurological manifestations is important, although their penetrance is not yet clear.
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PMID:Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and a review of the literature. 2511 28

Background: Genetic studies of late-onset sporadic ataxias (>40 years of age) are not routinely indicated. For unresolved cases, next-generation sequencing (NGS) tools, such as whole-exome sequencing (WES), are available for a definitive diagnosis. Case presentation: Our patient is a woman with a usual facial phenotype and anthropometry, who developed ataxia at 45 years of age, with no relevant family history and an initial clinical approach that ruled out common aetiologies. WES was performed when the patient was 54 years old. The results identified the heterozygous pathogenic variant c.248delA (p.N83MfsX4) in the nuclear receptor-binding SET domain protein 1 (NSD1; MIM 606681) gene (related to Sotos syndrome), which was not associated with ataxia and is not related to the patient's phenotype. Sanger sequencing of NSD1 in two different laboratories confirmed the variant. Conclusions: NGS findings generally offer valuable information that can be used for clinical decision-making. However, an incidental finding that leads to defining new clinical and bioethical actions is also possible. Consequently, the biological importance of this type of genetic "incidentalome" must be determined.
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PMID:Incidentalome in Neurogenetics: Pathogenic Variant of NSD1 in a Patient With Spinocerebellar Ataxia (SCA). 2959 81