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

• Cross Syndrome
• Depigmentation-Gingival Fibromatosis-Microphthalmia
• Oculocerebral-Hypopigmentation Syndrome

What is Oculocerebral Syndrome with Hypopigmentation? (Definition/Background Information)

• Oculocerebral Syndrome with Hypopigmentation is an extremely rare, genetic disorder characterized by decreased hair and skin color (hypopigmentation). It is also known as Cross-McKusick-Breen Syndrome, or simply, Cross Syndrome
• These signs are often accompanied by central nervous system (CNS) abnormalities along with slow mental and physical development. The disorder can be severe and cause complications that often include impaired vision, breathing difficulties, and abnormalities of the urinary tract
• Oculocerebral Syndrome with Hypopigmentation is an autosomal recessive genetic disorder; thus, having parents, who both carry the gene responsible for the disorder, is a predisposing factor
• Treatment measures for this disorder target the symptoms and may include surgery for enlarged gums, corrective lenses for vision defects, and the use of high SPF sunscreen for skin sensitivity
• Oculocerebral Syndrome with Hypopigmentation is an extremely rare disorder and little is known about its prognosis. However, on the cases reviewed, the prognosis was poor

Who gets Oculocerebral Syndrome with Hypopigmentation? (Age and Sex Distribution)

• Oculocerebral Syndrome with Hypopigmentation is a highly infrequent congenital disorder. The signs and symptoms of the condition are apparent at birth, which then affect the individuals throughout their lives
• Both males and females can be affected and no preference is observed
• All races and ethnic groups can be affected by Oculocerebral Syndrome with Hypopigmentation

What are the Risk Factors for Oculocerebral Syndrome with Hypopigmentation? (Predisposing Factors)

The risk factors for Oculocerebral Syndrome with Hypopigmentation may include:

• Having a family history of the condition
• Both parents being carriers of the condition (without displaying any symptoms)
• Parents, who are closely related to each other by blood

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 Oculocerebral Syndrome with Hypopigmentation? (Etiology)

Oculocerebral Syndrome with Hypopigmentation is a genetic disorder caused by the inheritance of a defective gene from each parent.

• Thus, it is inherited in an autosomal recessive manner. This means that if both parents are asymptomatic carriers of the disorder, there is a 1 in 4 chance that a child born to them will display symptoms of the disorder
• If one normal gene and one defective gene is present, the individual will not display symptoms of Oculocerebral-Hypopigmentation Syndrome, but will be a carrier

Autosomal recessive: 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 Oculocerebral Syndrome with Hypopigmentation?

The signs and symptoms of Oculocerebral Syndrome with Hypopigmentation are manifested at birth. The indications can vary from one individual to another and may include:

• Decreased skin or hair color (hypopigmentation) or an absence of skin and hair color (depigmentation). The skin may also be sensitive to sun exposure
• Infants with Oculocerebral Syndrome with Hypopigmentation may be extremely sensitive to light
• Abnormally slow mental and physical development
• Central nervous system abnormalities affecting the brain including:
  • Slow, involuntary movements (athetoid movements)
  • Impaired coordination associated with voluntary movements (ataxia)
  • Head movement beyond a normal range of motion (hyperextension)
  • Increased muscle rigidity and stiff movement
  • Exaggerated reflexes
• Lack of leg and arm voluntary movements (spastic tetraplegia)
• Permanently flexed joints (joint contractures) usually affecting the legs, arms, hips, and shoulders
• Infants with the condition may have a high-pitched cry or make a constant sucking sound
• Abnormalities of the eye that include:
  • One or both the eyes may be abnormally small (microphthalmia). The cornea of the eyes may be small as well, resulting in vision problems
  • Eyes may appear to have lost transparency (presence of cataracts)
  • Rapid involuntary eye movement from side-to-side (horizontal nystagmus)
  • Outward folding eyelids causing the membrane which is in contact with the eyeball to be exposed (ectoprion palpebral conjuctiva)
• Abnormally large gums that may be:
  • Pink, leathery, and have small bumps
  • Gums may completely cover the teeth resulting in speaking, breathing, and swallowing problems
• The head has an elongated appearance (dolichochephaly)
• Highly arched roof of the mouth
• Widely spaced teeth

How is Oculocerebral Syndrome with Hypopigmentation Diagnosed?

A diagnosis of Oculocerebral Syndrome with Hypopigmentation may be made through the following observations and tests:

• A careful physical examination and assessment of the child’s family (medical) history
• Assessment of the signs and symptoms presented by the child: This could include the presence of silver or grey hair in infants accompanied by neurological or ocular abnormalities including:
  • Slow, involuntary movements (athetoid movements)
  • Impaired coordination associated with voluntary movements (ataxia)
  • Head movement beyond a normal range of motion (hyperextension)
  • Increased muscle rigidity and stiff movement
  • One or both eyes may be abnormally small (microphthalmia)
  • The cornea of the eyes may be small as well resulting in vision problems
  • Eyes may appear to have lost transparency (cataracts)
  • Rapid involuntary eye movement from side-to-side (horizontal nystagmus)
  • Outward folding eyelids revealing membrane in contact with the eyeball (ectoprion palpebral conjuctiva)
  • Lack of leg and arm voluntary movements (spastic tetraplegia)
  • Exaggerated reflexes
  • Permanently flexed joints (joint contractures) usually affecting the legs, arms, hips, and shoulders
• Imaging techniques: CT scans to observe internal abnormalities such as underdevelopment of the diaphragm
• Molecular genetic testing to detect the presence of the mutant gene causing Oculocerebral Syndrome with Hypopigmentation

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 Oculocerebral Syndrome with Hypopigmentation?

The possible complications of Oculocerebral Syndrome with Hypopigmentation may include:

• Impaired vision or blindness
• Learning disabilities
• Impaired physical development
• Severe breathing and feeding problems from enlarged gums
• Breathing difficulties associated with an underdeveloped diaphragm
• Urinary tract abnormalities
• Emotional stress that can affect the quality of life

How is Oculocerebral Syndrome with Hypopigmentation Treated?

Treatments for Oculocerebral Syndrome with Hypopigmentation are directed toward the specific signs and symptoms that are observed. It often requires the coordinated effort of various specialties including pediatricians, neurologists, dermatologists, ophthalmologists, and dentists.

The treatment measures may include the following:

• Surgeries may be required to reduce the size of the gums: Gums may enlarge again with the onset of the child’s second set of teeth (permanent teeth)
• High SPF sunscreen, hats, and long-sleeve shirts are recommended as the affected individuals may have highly-sensitive skin
• Glasses or contact lenses may be necessary to correct defective vision

It is important that children with Oculocerebral Syndrome with Hypopigmentation be diagnosed early in order for appropriate treatment measures to be instituted. This may involve the aid of medical, remedial education, social or vocational services. This can help allow them to develop to their full potential.

How can Oculocerebral Syndrome with Hypopigmentation be Prevented?

• Currently, there are no specific methods or guidelines to prevent Oculocerebral Syndrome with Hypopigmentation, since it is a genetic condition
• 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 such as Oculocerebral Syndrome with Hypopigmentation

What is the Prognosis of Oculocerebral Syndrome with Hypopigmentation? (Outcomes/Resolutions)

• Oculocerebral Syndrome with Hypopigmentation is extremely rare, thus very little is known about the prognosis of this disorder
• Medical literature reports only 2 individuals, one in the teens and one in the twenties, with Oculocerebral Syndrome with Hypopigmentation. The reports indicate that both the individuals are deceased now

Additional and Relevant Useful Information for Oculocerebral Syndrome with Hypopigmentation:

In one case, it was reported that two sibling suffered from Oculocerebral Syndrome with Hypopigmentation. Yet a third sibling had the grey-silver hair and hypopigmentation indicative of Oculocerebral Syndrome with Hypopigmentation, but had no other (CNS) symptoms.