On this page, you will find information about a genetic change that was identified in a UDN participant. We are trying to find others with the same or similar condition. (Sharing information on this website is not a requirement of UDN participation. Only descriptions of participants who give explicit consent will appear here.)

Does this patient sound like someone you know?
Date of Report November 21, 2016
Full Gene Name Potassium voltage-gated channel subfamily D member 3
Location Chromosome 1 (1p13.2)
Ideogram: KCND3 gene on chromosome 1

Click to enlarge ideogram in new window (generated using the NCBI Genome Decoration Page )
Function The KCND3 gene codes for an alpha subunit of a voltage-gated potassium channel (Lee et al., 2012 ).
Database Links GeneCards: GC01M11177 NCBI Gene: 3752 OMIM: 605411 UniProtKB/Swiss-Prot: Q9UK17
Clinical Significance Changes in the KCND3 gene have been found in individuals with Brugada syndrome 9 and spinocerebellar ataxia 19.
A change in the KCND3 gene was also identified in a UDN participant. Research is underway to see if this change is causing symptoms in this patient.

The participant, a 49-year-old female with muscle weakness, balance problems, clumsiness, muscle twitching (fasiculations) and cramps, abnormal heart rhythm (second-degree AV block), episodes of high potassium (hyperkalemia), restrictive lung disease, double vision (diplopia), and seizures was found to carry the following genetic change in the KCND3 gene: c.1348C>T/ p.L450F.
Gene Inheritance Pattern Position Transcript DNA Change Protein Change
KCND3 Autosomal dominant chr1: 112323335 NM_004980 c.1348C>T p.L450F
The patient was in excellent health until age 45 when she started to notice muscle weakness and difficulty keeping up while playing sports. Her muscle weakness has continued to worsen and she now has balance problems, muscle twitching (fasciculations) and cramps, and difficulty with coordination. She has significant respiratory muscle weakness and requires nocturnal bi-level ventilation (BiPAP).

The patient has double vision (diplopia on lateral gaze) with weakness (opthalmoplegia) and started having seizures (left temporal lobe focus). These seizures are now controlled with carbamazepine treatment and a pacemaker.

The patient also has an abnormal heart rhythm (second-degree AV block) and had a pacemaker implanted at age 48. Based on recent imaging findings, she has probable early heart disease (cardiomyopathy).

She has been diagnosed with a potassium channel disease (channelopathy) with impaired renal excretion, and has had several episodes of extreme high potassium (hyperkalemia) with dramatic ECG changes, respiratory failure, and very low serum phosphate.

The patient also has stage 3 thyroid cancer (multifocal papillary).

Some of her other features include:

  • Protruding shoulder blades (scapular winging)
  • Abnormal muscle biopsies (abundance of “moth eaten” fibers, increased sub-sarcolemmal accumulation of mitochondria, disruption of internal architecture of type II fibers)
  • Cytochrome c oxidase deficiency
  • Multiple mitochondrial DNA deletions
  • Low blood sugar (hypoglycaemia)
  • Low white blood cell levels (leukopenia)
  • Low lymphocyte levels (lymphopenia)
  • Mild anemia (likely hemolytic)
  • Cerebral folate deficiency (high levels of anti-folate antibodies)
  • Elevated IgM
  • Raynaud’s disease
  • Abnormal calcification in the kidneys (diffuse renal cortical nephrocalcinosis with retraction and scarring of cortex)
  • Low urea excretion in urine
  • High creatinine excretion in urine
  • Amino acid abnormalities (elevated amino acid levels in urine, decreased amino acid levels in cerebrospinal fluid)
Do you think this profile matches someone you know? Contact us via email or phone.

Email: UDN@hms.harvard.edu
Phone: 1 844 Ring UDN (1 844 746 4836)