Cohen syndrome (also known as Pepper syndrome or Cervenka syndrome) is a very rare

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

genetic disorder with varied expression, characterised by

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

, intellectual disability, distinct craniofacial abnormalities and potential ocular dysfunction.

Signs and symptoms

Genetics

This syndrome is caused by pathogenic variants (

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s) in the VPS13B

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

at chromosomal locus 8q22. It has an

transmission with variable expression. Variants in VSP13B also cause Mirhosseini–Holmes–Walton syndrome, which is now considered to be the same entity as Cohen syndrome

Diagnosis

Cohen syndrome is diagnosed by clinical examination but is often difficult due to variation in expression. Ocular complications, though rare, are listed as

optic atrophy Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain. Damage and death of these nerve cells, or neurons, leads to characteristic featu ...

microphthalmia Microphthalmia (Greek: grc, μικρός, mikros, small, label=none, grc, ὀφθαλμός, ophthalmos, eye, label=none, also referred as microphthalmos, is a developmental disorder of the eye in which one (unilateral microphthalmia) or both ( ...

pigment A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compo ...

ary chorioretinitis,

hemeralopia Hemeralopia (from Greek ''ημέρα'' hemera, "day", and ''αλαός'' alaos, "blindness") is the inability to see clearly in bright light and is the exact opposite of nyctalopia (night blindness), the inability to see clearly in low light. Heme ...

(decreased vision in bright light),

myopia Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...

, strabismus, nystagmus and iris/

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

l coloboma. General appearance is obesity with thin/elongated arms and legs.

micrognathia Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorm ...

, short

philtrum The philtrum ( la, philtrum from Ancient Greek ''phíltron,'' lit. "love charm"), or medial cleft, is a vertical indentation in the middle area of the upper lip, common to therian mammals, extending in humans from the nasal septum to the tubercl ...

and high vaulted palate are common. Variable intellectual disability with occasional

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

and

deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an audiological condition. In this context it is written ...

also is characteristic of Cohen syndrome.

Management

Some of the symptoms of Cohen syndrome can be addressed through early intervention with medical specialists. Those who have this disease may benefit from early exposure to speech, physical, and occupational therapy to correct symptoms such as joint overflexibility, developmental delays, hypotonia, and motor clumsiness. Diagnosis may potentially be delayed due to the lack of a definitive molecular test as well as the clinical variability of published case reports. Glasses are beneficial to those who have severe nearsightedness, whereas individuals with retinal degeneration need training for the visually impaired, which is usually more beneficial when this is addressed at a young age. Younger patients start out having unimpaired vision, but it starts to deteriorate at a young age and does so slowly. If vision is able to improve with the use of glasses, they should be worn to help facilitate concept development. Retinal degeneration cannot be ameliorated with glasses. The type of therapy needed for each individual varies, as not every affected individual would benefit from speech, physical, and occupational therapies. The type of therapy for each person is highly individualized. Individuals who have Cohen syndrome may also benefit from psychosocial support. Many people who have Cohen syndrome also have neutropenia which is a condition in which an individual has an abnormally low number of white blood cells called neutrophils. Having this condition may make these individuals susceptible to infections. Granulocyte-colony stimulating factor (G-CSF) is one possible treatment for neutropenia. Monitoring weight gain and growth is crucial, as well as annual ophthalmologic and hematologic evaluations and checkups. While there are treatments available to people with Cohen syndrome, there are no known cures for the disease.

Prevalence

Over the past several years, there have been approximately 50 new cases worldwide. There are population groups with this condition in Australia, New Zealand, the UK and the US. It still seems to go undiagnosed, leaving the number of known cases less than 500.

Etymology

The syndrome is named after Michael Cohen, William Pepper and Jaroslav Cervenka, who researched the illness.

References

External links

GeneReview/NIH/UW entry on Cohen syndrome
{{Inherited disorders of trafficking Inherited disorders of trafficking Syndromes with intellectual disability Syndromes with obesity Syndromes with craniofacial abnormalities Rare syndromes