Timothy C. Hain, MD Page last modified: March 3, 2019
Kearns-Sayre syndrome (abbreviated KSS) is a disease caused by a deletion in the mitochondrial DNA. It is a "progressive external ophthalmoplegia", or PEO. The "external" in the PEO, means that the pupil continues to react (as it is "internal"), but the eye muscles are paralyzed (the external part). KSS is rare (Chinnery et al., 2004). Ptosis (droopy eyes) is the most common complaint (Tsang et al, 2018)
Another acronym used in these conditions is "CPEO" which stands for chronic progressive external opthalmoplegia.
KSS and PEO are distinct from "bulbar palsies", because KSS and PEO involve the eyes alone, while bulbar palsies involve more muscles in the face.
To account for the variability of KSS, the acronym "CPEO-plus" has been coined, meaning that in addition to the PEO, there may be cerebellar ataxia, pyramidal signs, sensorineural hearing loss, optic atrophy, pigmentary retinopathy, cardiomyopathy, cardiac conduction defects, thyroid disturbance, and diabetes.
KSS is just one of these, and it names the triad of CPEO, pigmentary retinopathy, and an early age of onset (<30).
Early death -- think in the 20's -- mainly occurs due to heart block. (Trivedi et al, 2018)
The essence of diagnosing KSS lies in noting a PEO developing before the age of 20 years of age, with ptosis (droopy eyelids), accompanied by retinitis pigmentosa. KSS may affect either gender. Although mitochondrial disorders are usually inherited from the mother, in KSS, this pattern is generally not found.
In PEO, the eyes don't move under ANY circumstances -- neither voluntarily or reflexively. In PEO, there is no "dolls head reflex". See the movie below for an example.
Supplemental material on the site DVD: Another Movie of PEO due to mitochondiral myopathy. Muscle biopsy showed COX deficient and ragged red fibers. Courtesy of Dr. Dario Yacovino.
Accompanying the PEO can be cardiac conduction problems (i.e. heart arrythmia), ataxia and cerebellar signs (Vedanarayanan, 2003), deafness (Kokotas et al, 2007), and brainstem disorders (i.e. the CPEO+ mentioned above". Spinal fluid protein may be > 100, but this is a nonspecific sign. There may also be short stature and have deafness.
Regarding eye exams, according to Zhu et al, only about 16% of patients with genetic mitochondrial mutations have pigmentary retinopathy (2018). The pigmentary retinopathy helps with diagnosis, but it usually does not affect visual acuity. PEO was noted in only 8%. Thus, it seems that there are far more people with genetic mutations, than manifest with the classic KSS type picture.
Diabetes is common, particularly in the MELAS subgroup (about 32%, Al-Gadi et al, 2018).
White matter disorders are always present in KSS (Filostito, 2007).
Cyclic vomiting is rarely encountered in KSS (Boles, 2007)
Muscle biopsy in KSS as well as other mitochondrial myopathies shows "ragged red" fibers. This typically involves taking a large "chunk" of muscle, and we don't think this should be pursued lightly.
The genetics generally are characterized by a large deletion of variable size within the mitochondrial DNA of skeletal muscle. As mitochondria have their own DNA, and is inherited from the mother, KSS is inherited from the mother. Mitochondrial deletions occur in roughly 1/8000 persons (Chinnery et al., 2004).
Larger deletions of mitochondrial DNA cause more issues such as cerebellar ataxia, heart block for example.
CPEO combined with bilateral optic atrophy suggets a mutation in OPA1, the nueclear gene responsible for most cases of dominant optic atrophy. The combination of CPEO with recurrent stroke like episodes suggests a mutation in the mitochondrial transfer RNA for leucine, most commonly the A3243G mutation, also responsible for MELAS (see below).
Several nuclear and mitochondrial CPEO mutations cause a combination fo CEPO with cerebellar ataxia, including nuclear mutations in POLG1, and a variety of other miscellaneous mutations. (Kung et al, 2017). None of these genetic disorders has a specific treatment, but once they are documented, the expensive search for a cause can stop.
There are a high number of references concerning Kearns-Sayre in the literature (more than 900 in Pubmed as of 2019). Thus it is not for lack of study that KSS has no effective treatment. As is the case for most genetic disorders, at present all we have is supportive treatment. Vigilance is needed regarding the cardic disorders as a pacemaker may be indicated at some point, surgery may be needed to correct eye lid weakness, and hearing aids are commonly used for the hearing loss when it occurs.
One would think that effective treatment would involve inserting in functional genes into mitochondria. This is likely tougher than inserting in functional genes into nuclear DNA, and thus may take quite a long time as genetic medicine is developed.
Several authors (Rodriguez et al 2007, Komura, 2003; Choi et al, 2000) suggested a benefit for nutritional supplements such as creatine or coenzyme-Q. As there are potential adverse health effects of creatine, we suggest that persons with KSS who wish to pursue this treatment do this under supervision of a physician who is familiar with KSS (and there are not very many of these !).
In individuals with heart block, an implantable cardiac device may be suggested (Imamura et al, 2019). This seems rather reasonable to us.