Tag Archives: Genetic

Hereditary sensory neuropathy HSN (Hereditary sensory autonomic polyneuropathy HSAN)

Synonyms: Hereditary sensory neuropathy HSN or Hereditary sensory autonomic polyneuropathy HSAN Diagnosis: Clinical +genetic testing Clinical features: All have sensory neuropathy without motor features HSN1 a.k.a. Denny-Brown neuropathy: Clinical features: Loss of pain and temperature sensation, ulceration of feet and hands, Charcot joints. No autonomic features Findings on investigations: NCS/EMG: axonal HSN2 a.k.a. congenital sensory … Continue reading Hereditary sensory neuropathy HSN (Hereditary sensory autonomic polyneuropathy HSAN)

Charcot-Marie-Tooth disease CMT

Synonyms: Hereditary Motor and Sensory Neuropathy HMSN Now the whole group is called Charcot-Marie-Tooth disease CMT Diagnosis: Clinical +electrodiagnostics (EMG/NCS) +Genetic testing: Clinical features: Abnormal LMN features: weakness Atrophy: champagne-glass legs, stork legs Deformity: claw toe, Friedreich’s foot, kyphoscoliosis Sensory features: loss of vibration and later on loss of proprioception Palpable nerves Genetics: CMT1 a.k.a. … Continue reading Charcot-Marie-Tooth disease CMT

Heredofamilial Brachial Plexopathy

Synonyms: a.k.a. hereditary brachial plexus neuropathy a.k.a. hereditary neuralgic amyotrophy HNA, rare: Clinical features: Usually Painless Attacks of weakness with recovery over weeks +some cranial involvement Genetics: Mapped to chr. 17q24-25 Autosomal dominant Findings on investigations: NCS/EMG: may be normal between attacks Pathology, nerve biopsy: Semithin plastic sections: Tomacula (sausage like excess myelin) Teased fibres: … Continue reading Heredofamilial Brachial Plexopathy

Spinal and bulbar muscular atrophy, Kennedy disease

Synonyms: Spinal and bulbar muscular atrophy (SBMA), Kennedy disease Diagnosis: This is a clinical diagnosis supported by NCS/EMG Clinical features: Lower motor neuron (LMN) disease Muscle atrophy, weakness, contraction fasciculations, and bulbar involvement Gynecomastia, testicular failure Genetics: Androgen receptor (AR) gene, expansion of CAG trinucleotide repeat Related articles: Approache to weakness, nerve diseases, Amyotrophic lateral … Continue reading Spinal and bulbar muscular atrophy, Kennedy disease

Spinal Muscular Atrophy

Synonyms: see eponyms under subtypes Diagnosis: A form of motor neuron disease Genetics: SMN1 gene chr. 5 (survival motor neuron gene), autosomal recessive with modifier genes, Modifier genes: SMN2 gene number of copies, Subtypes: SMA1 a.k.a. Werdnig-Hoffman disease: onset at birth or prenatally, hypotonia frog-like leg posturing, respiratory muscle paralysis SMA2 a.k.a. intermediate: onset at … Continue reading Spinal Muscular Atrophy

Familial amyloid polyneuropathy FAP

Synonyms: a.k.a. Familial amyloidotic polyneuropathy FAP, a.k.a. Hereditary amyloid neuropathy Diagnosis: Biopsy plus genetic testing Types of familial amyloid polyneuropathy: Transthyretin amyloidosis Apolipoprotein A-I Gelsolin   Transthyretin amyloidosis a.k.a. amyloidogenic mutated transtyretin ATTR: TTR gene mutation, protein= transthyretin, autosomal dominant Clinical features: Polyneuropathy: Autonomic, symmetric mainly sensory polyneuropathy (pain and temperature dysfunction >proprioception/vibration) Genetics: Transtyretin … Continue reading Familial amyloid polyneuropathy FAP

Tuberous Sclerosis

Synonyms: a.k.a. Bournvile disease Genetics: Genetic tests: chr. 9q34 TSC1 encoding hamartin , chr. 16p13 TSC2 encoding tuberin Diagnosis: Clinical features plus findings on investigations Clinical  features: Seizures Retinal hamartomas Skin: Hypopigmented macules a.k.a. ‘Ash leaf shaped’, easier to see with Wood lamp (UV light)= poliosis (white hair) on the scalp Ungal fibromas, shagreen patches … Continue reading Tuberous Sclerosis

Familial Hyperekplexia

Synonyms: a.k.a. Familial startle disease Diagnosis: This is a clinical diagnosis Genetics: Autosomal dominant, autosomal recessive (frame shift) Glycine Receptor alpha subunit GLRA1 5q32 Clinical features: Infants: stiff (except when sleeping), excessive startle response Older patients: Sudden myoclonus or falling Spastic paraparesis in one family Precipitated by sudden stimuli Treatment: Responds to benzodiazepines Related articles: … Continue reading Familial Hyperekplexia

Fatal Familial Insomia

Diagnosis: Combination of clinical features and imaging Genetics: Autosomal dominant Clinical features: Insomnia, sympathetic over activity, impaired attention Ataxia, dysarthria, Memory loss Hormone abnormalities: increased cortisol, Polysomnography: reduced total sleep time, absent REM sleep, absent deep nonREM sleep, Findings on Investigations: MRI: Normal or cerebral or cerebellar atrophy PET: Decreased metabolism in the thalami CSF: … Continue reading Fatal Familial Insomia

Progressive Myoclonic Epilepsy (PME)

Unverricht-Lundborg a.k.a. Baltic myoclonus Myoclonic epilepsy and ragged red fibres Lafora disease Neuronal ceroid lipofuscinosis Gaucher disease GM2 Gangliosidosis, hexosaminidase deficiency Sialidosis Juvenile neuroaxonal atrophy Dentatorubral-Pallidoluysian atrophy Related articles: Approach to cognitive impairment, Epilepsy,  

Neuronal Ceroid Lipofuscinosis

Synonyms: Jansky-Bielschowsky, (Spielmeyer-Vogt-Sjogren) Batten, (Parry) Kuf, Santavori Diagnosis: A group of lysosomal storage disorders Types: Infantile INCL Type 2: Late infantile LINCL a.k.a. Classic a.k.a. Jansky-Bielschowsky disease Type 3: Juvenile JNCL a.k.a. Spielmeyer-Vogt-Sjogren disease, or Batten disease Type 4: Adult ANCL a.k.a. Kuf’s disease, or Parry disease. No visual failure Type 5: Finish variant Genetics: … Continue reading Neuronal Ceroid Lipofuscinosis

GM2 Gangliosidosis, Hexosaminidase Deficiency

Diagnosis: A type of lysosomal storage disease. Also a sphingolipidosis. Subtypes: Tay-Sachs disease: hexosaminidase A gene mutation, HEXA gene chr. 15q, encodes the alpha subunit Sandhoff disease: hexosaminidase B gene mutation, HEXB gene chr. 5q, encodes the beta subunit AB variant a.k.a. GM2 activator deficiency: GM2A gene chr. 5q, encodes activator protein Related articles: Epilepsy,

Gaucher Disease

Synonyms: a.k.a. Glucosylcerebrosidase deficiency Diagnosis: A type of lysosomal storage disease. A type of sphingolipidosis. Also a type of Progressive myoclonic epilepsy Genetics: Autosomal recessive Subtypes: Type 1 Type 2, absent enzyme activity Type 3, “neurological”: Supranuclera gaze palsy, myoclonus, no dementia Splenomegaly, pancytopenia Pathology: Ectopic dendritogenesis, meganeurites Treatment: Options as below Enzyme replacement therapy: … Continue reading Gaucher Disease

Myoclonic Epilepsy and Ragged Red Fibres (MERRF)

Genetics: mitochondrial DNA mutation Diagnosis: A form of progressive myoclonic epilepsy Clinical features: Myopathy, neuropathy Deafness Lipomas Optic atrophy Myoclonus Genetics: Familial, sporadic, maternal Mitochondrial DNA mutation Pathology: Ragged red fibres in muscle. Changes in Dentate nucleus & inferior olive Related articles: Epilepsy, mitochondrial disorders,