A new patient with Andermann syndrome: an underdiagnosed clinical genetics entity?

Summary: A new patient with Andermann syndrome: an underdiagnosed clinical genetics entity .': Andermann syndrome is an autosomal recessive disorder characterized by the agenesis of the corpus callosum and peripheral neuropathy (ACCPN). People affected by Andermann syndrome have mental retardation, areflexia and severe progressive neuropathy often accompanied by psychiatric symptoms, and they typically die in the third decade of their life. We here report the case of a 5 year-old Turkish boy bom to consanguineous parents. He presented to clinical attention with delayed development and epilepsy and was found to have dysmorphic characteristics, areflexia and severe neuropathy on exam. Imaging studies were remarkable for agenesis of corpus callosum. SLCI2A6 screening revealed the presence of R101IX mutation; potentially responsible for the changes in intracellular and extracellular ion concentrations, leading to defects in cortical electrical activity.Key-words: Andermann Syndrome - EEG - SLCI2A6INTRODUCTIONPeripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) or Andermann syndrome is an autosomal recessively inherited progressive disorder mostly seen in French-Canadians (FC) living in Saguenay-Lac-St-Jean and Charlevoix, Quebec. In the first years of life the symptoms include slow developmental progress, mental retardation, areflexia and dysmorphic characteristics. Between 4 and 6 years of age they are able to walk with support, later on, severe progression of motor and intellectual disabilities are observed along with psychiatric symptoms such as hallucinations, suggesting a progressive deterioration in the central nervous system. Affected individuals typically die in the third decade of their life (5, 11). In 2002, Howard et al. showed mutations in solute carrier family 12 member 6 (SLC12A6) gene, encoding the potassium-chloride (K+-C1) cotransporter 3 (KCC3) protein, to be causative in the ACCPN syndrome (11). Other than the French-Canadian population, Andermann syndrome is reported to be most prevalent among Turkish patients. Here we report the presence of a R101IX mutation in a 5 year-old Turkish boy who presented to medical attention at 1 year-of-age with delayed development and epilepsy.CASE REPORTA one year-old boy was admitted to the child neurology clinic because of developmental delay. He was prematurely bom at week 31 at 2200 g through vaginal delivery. He was not reported to have newborn jaundice nor perinatal asphyxia, and did not need an incubator or ventilator. He did not speak any words and was reported to smile at 8 months, developed head control at 5 months and was able to sit up without support at 12 months. He was the second living child of third-degree consanguineous parents. The mother was 26 years old at the time with a healthy 8 year-old daughter and she also had a history of a terminated intrauterine pregnancy (via D&C) at 6-months reportedly due to a fetal brain abnormality. Of note, the 30 year old father has a childless sister with mild mental retardation and a 20 year-old brother with moderate mental retardation who continues to receive special education.On physical examination, the patient had dysmorphic characteristics which included hypertelorism, long face, slight ptosis, a high arched palate, separated teeth, proximally placed thumbs. He had absent deep tendon reflexes (Fig. 1). The rest of the physical exam was unremarkable. Laboratory values including complete blood count, biochemistry tests including creatine kinase, thyroid function tests, urine and plasma aminoacid levels were all normal. Agenesis of corpus callosum was detected by magnetic resonance imaging (MRI).The patient, who continues to receiving special education, began to say a few words at 2 years. At 4 years of age, a electrophysiological study was performed which revealed demyelinization and axonal damage consistent with severe sensorimotor polyneuropathy. …