Andermann syndrome
Andermann syndrome is a hereditary motor and sensory neuropathy with agenesis of the corpus callosum that causes severe progressive weakness, sensory loss, and reduced life expectancy.
Overview
Andermann syndrome is a disorder that damages the nerves used for muscle movement and sensation (motor and sensory neuropathy). The neuropathy results from poor development of nerves, especially those that control movement, which are only about half their normal size. Most individuals have absence (agenesis) or malformation of the tissue connecting the left and right halves of the brain (corpus callosum). Because of these features, the condition is also called hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC).
Symptoms
- Abnormal or absent reflexes (areflexia)
- Weak muscle tone (hypotonia)
- Muscle wasting (amyotrophy)
- Severe progressive weakness and loss of sensation in the limbs
- Rhythmic shaking (tremors)
- Delayed walking (typically 3–4 years) followed by loss of ambulation in teenage years
- Joint deformities (contractures) and spinal curvature (scoliosis)
- Cranial nerve problems: facial muscle weakness, drooping eyelids (ptosis), gaze palsy
- Intellectual disability (mild to severe)
- Seizures
- Psychiatric symptoms in adolescence (depression, anxiety, agitation, paranoia, hallucinations)
- Atypical physical features:
- Widely spaced eyes (ocular hypertelorism)
- Wide, short skull (brachycephaly)
- High‑arched hard palate
- Big toe crossing over other toes (hallux valgus)
- Partial fusion (syndactyly) of the second and third toes
Causes & Risk Factors
Pathogenic variants (mutations) in the SLC12A6 gene cause Andermann syndrome. The gene encodes the K‑Cl co‑transporter protein KCC3, which moves potassium (K⁺) and chloride (Cl⁻) ions together across cell membranes in an electroneutral fashion. Although the precise physiological role of KCC3 is unknown, it is critical for the development and maintenance of nerve tissue and for regulating axonal function.
Disruptive variants in SLC12A6 impair KCC3 function, interfering with corpus callosum development and the maintenance of peripheral nerves, leading to the clinical manifestations of the disorder.
The condition is inherited in an autosomal recessive pattern: both copies of the gene must carry variants. Parents are typically carriers without symptoms.
Andermann syndrome is most prevalent in the French‑Canadian population of the Saguenay‑Lac‑St‑Jean and Charlevoix regions of northeastern Quebec, occurring in almost 1 in 2,000 newborns there. Only a few cases have been identified elsewhere.
Diagnosis
Diagnosis relies on clinical recognition of the characteristic neuropathy, agenesis of the corpus callosum, and associated features, followed by confirmation through genetic testing that identifies pathogenic variants in SLC12A6. Relevant genetic testing resources include the Genetic Testing Registry entry for “Agenesis of the corpus callosum with peripheral neuropathy.”
Treatment & Management
The source material does not detail specific therapeutic interventions. Management typically focuses on supportive care for neuromuscular, orthopedic, and psychiatric complications, as well as monitoring respiratory function given the association with reduced life expectancy.
Other Names
- ACCPN
- Agenesis of corpus callosum with neuronopathy
- Agenesis of corpus callosum with peripheral neuropathy
- Agenesis of corpus callosum with polyneuropathy
- Charlevoix disease
- Hereditary motor and sensory neuropathy with agenesis of the corpus callosum
- HMSN/ACC
Additional Information & Resources
Genetic Testing Information
- Genetic Testing Registry: Agenesis of the corpus callosum with peripheral neuropathy
Genetic and Rare Diseases Information Center
- Corpus callosum agenesis‑neuronopathy syndrome
Patient Support and Advocacy Resources
- National Organization for Rare Disorders (NORD)
Catalog of Genes and Diseases from OMIM
- AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY; ACCPN
Scientific Articles on PubMed
- PubMed