What are the other Names for this Condition? (Also known as/Synonyms)

• Cleft Lip/Palate-Syndactyly-Pili Torti Syndrome
• Ectodermal Dysplasia, Cleft Lip and Palate, Mental Retardation, and Syndactyly
• Zlotogora-Ogur Syndrome

What is Zlotogora Syndrome? (Definition/Background Information)

• Zlotogora Syndrome, also known as Zlotogora-Ogur Syndrome, is an ectodermal dysplasia syndrome characterized by hair, skin and teeth anomalies, facial dysmorphism with cleft lip and palate, cutaneous syndactyly and, in some cases, intellectual disability
• Zlotogora Syndrome is a congenital disorder characterized by sparse and twisted hair (pili torti) and absent or sparse eyebrows, hypohidrosis, dry skin, palmoplantar keratoderma, abnormal teeth (delayed eruption, microdontia/hypodontia, and anodontia in adults), facial dysmorphism (protruding and malformed ears, micrognathia, bilateral cleft lip and palate), cutaneous syndactyly (fingers and toes) and transverse crease on the palms. Onychodystrophy may be present
• Additional features including intellectual disability, deafness, hypoplastic lacrimal puncta, nipple anomalies, genitourinary abnormalities (hypoplastic scrotum and presence of the testes in the inguinal canal), and lumbar lordosis may be observed
• Zlotogora Syndrome and Margarita Island ectodermal dysplasia are the same entity

(Source: Zlotogora-Ogur Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Zlotogora Syndrome? (Age and Sex Distribution)

• Zlotogora Syndrome is an extremely rare congenital disorder, with less than 60 cases reported worldwide
• The onset of symptoms may occur at birth or in infancy
• Both males and females may be affected
• The disorder is frequent on Margarita Island due to a founder effect

What are the Risk Factors for Zlotogora Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Zlotogora Syndrome can be inherited
• Children of consanguineous parents may bear an increased risk of being born with this syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Zlotogora Syndrome? (Etiology)

• Zlotogora Syndrome is caused by mutation(s) in the PVRL1 gene
• This gene codes for nectin-1, which is involved in cell to cell adhesion (with afadin,  and ponsin, known as the NAP-dependent cell to cell adhesion)
• The condition is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Zlotogora Syndrome?

The signs and symptoms of Zlotogora Syndrome may include:

• Abnormality of the philtrum
• Abnormality of the ear
• Anteverted ears
• Cleft palate
• Cleft upper lip
• Cutaneous finger syndactyly
• Cutaneous syndactyly of toes
• Microdontia
• Nail dysplasia
• Progressive hypotrichosis
• Sparse and thin eyebrow
• Sparse eyelashes

Very frequently present symptoms in 80-99% of the cases:

• Bilateral cleft lip and palate
• Ectodermal dysplasia
• Finger syndactyly
• Macrotia
• Macrotia
• Toe syndactyly

Frequently present symptoms in 30-79% of the cases:

• Abnormality of dental morphology
• Alopecia
• Bilateral single transverse palmar creases
• Carious teeth
• Downslanted palpebral fissures
• Dystrophic fingernails
• Dystrophic toenail
• Highly arched eyebrow
• Hypogonadism
• Hypoplasia of the zygomatic bone
• Intellectual disability
• Micrognathia
• Midface retrusion
• Neurological speech impairment
• Pili torti
• Protruding ear
• Recurrent respiratory infections
• Scrotal hypoplasia
• Sparse hair
• Sparse lateral eyebrow
• Synophrys
• Wide intermamillary distance
• Wide nasal bridge

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of dental enamel
• Abnormality of the ureter
• Anodontia
• EEG abnormality
• Hyperlordosis
• Hypodontia
• Hypohidrosis
• Palmoplantar hyperkeratosis
• Seizures

(Source: Zlotogora Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Zlotogora Syndrome Diagnosed?

Zlotogora Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative genetic mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Zlotogora Syndrome?

The complications of Zlotogora Syndrome may include:

• Severe intellectual disability
• Problems with chewing food due to dental abnormalities
• Low self esteem due to physical appearance

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Zlotogora Syndrome Treated?

There is no cure for Zlotogora Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Zlotogora Syndrome be Prevented?

Currently, Zlotogora Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Zlotogora Syndrome? (Outcomes/Resolutions)

• The prognosis of Zlotogora Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Zlotogora Syndrome:

• Alpha herpes viruses use nectin-1 to gain entry into human cells. The gene coding for nectin-1 is mutated in Zlotogora Syndrome
• Zlotogora Syndrome is also known by the following names:
  • Cleft Lip/Palate-Ectodermal Dysplasia Syndrome
  • Cleft Lip/Palate-Syndactyly-Pili Torti
  • Syndactyly-Ectodermal Dysplasia-Cleft/Lip palate
  • Zlotogora-Zilberman-Tenenbaum Syndrome

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/