Athena Diagnostics® is pleased to announce the addition of several new tests for Charcot-Marie-Tooth (CMT) disorder, leukodystrophy, mitochondrial disorders and developmental delay available now.
Charcot-Marie-Tooth (CMT) Disorder
Next Generation Sequencing Now Available
Charcot-Marie-Tooth (CMT) disorder is the most common inherited neuropathy, affecting 1 in 2,500 people world wide. Athena Diagnostics is pleased to introduce next generation sequencing to analyze 23 genes for CMT.
Our advanced sequencing platform is in 100 percent concordance with Sanger sequencing, providing a reliable measurement for CMT. Additionally, we will continue to analyze all variants of unknown significance through the Athena Insight bioinformatics program, providing expert interpretation of results.
Leukodystrophies are a group of rare genetic disorders characterized by a developmental anomaly of myelin growth in the brain. The most common symptom is a progressive decline in a child or infant that was developing normally, however, other common symptoms include progressive loss in body tone, movements, speech, gait, hearing and behavior.1
Mutations in the PDHA1 gene are a common cause of pyruvate dehydrogenase (PDH) deficiency,2 which is linked to heterogeneous symptoms ranging from severe neonatal lactic acidosis to childhood-adolescence progressive neurological disease (often including hypotonia, seizures and developmental delay) to intermittent ataxia.3 A metabolic profile may show elevated blood or cerebrospinal fluid lactate and pyruvate and elevated alanine, as well as decreased PDH activity.4 A confirmatory diagnosis allows for early intervention and informed reproductive decision making.
Abnormalities in the FOXG1 gene are associated with a congenital variant Rett syndrome which may present with severe developmental and psychomotor delay, severe postnatal microcephaly, jerky limb movements, strabismus, hypoplasia of the corpus callosum and generalized seizures.5,6 Unlike classic Rett syndrome, symptoms are present from birth without a recognizable history of regression.7 Separately, Athena offers both sequencing and duplication/deletion testing for MECP2 (associated with classic Rett syndrome) and CDKL5 (associated with atypical Rett syndrome).
MEF2C aberrations may cause severe developmental delay (autosomal dominant inheritance), seizures (which may include infantile spasms), dysmorphic facial features and brain structural abnormalities.8
1. Leukodystrophy. American Academy of Neurology Web site. http://patients.aan.com/disorders/index.cfm?event=view&disorder_id=974. Accessed April 1, 2013.
2. DeBrosse SD, Okajima K, Zhang S, et al. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype. Mol Genet Metab. 2012; 107(3):394-402.
3. Ostergaard E, Birk Moller L, Serap Kalkanoglu-Sivri H, et al. Four Novel PDHA1 mutations in pyruvate dehydrogenase deficiency. J Inherit Metab Dis. 2009; 32 (Suppl 1):S235-S239.
4. Gunel MK, Mutlu A, Tarsuslu T, et al. Relationship among the Manual Ability Classification System (MACS), the Gross Motor Function Classification System (GMFCS), and the functional status (WeeFIM) in children with spastic cerebral palsy. Eur J Pediatr. 2009; 168(4):477-485.
5. Kortüm F, Das S, Flindt M, et al. The core FOXG1 syndrome phenotype consists of postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and corpus callosum hypogenesis. J Med Genet. 2011; 48(6):396-406.
6. MA Mencarelli1, A Spanhol-Rosseto, R Artuso, et al. Novel FOXG1 mutations associated with the congenital variant of Rett syndrome. J Med Genet. 2010; 47:49-53.
7. Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010; 68(6):944-50.
8. M Zweiera, A Rauch. The MEF2C-Related and 5q14.3q15 Microdeletion Syndrome. Mol Syndromol. 2012; 2(3-5):164–170.