MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: unknown

Cross syndrome
Kramer syndrome
Oculocerebrocutaneous syndrome

Albinism
Mental retardation
Developmental delay
Sclerocornea
Spasticity
Blindness

Oculocerebrocutaneous Syndrome with Hypopigmentation

Clinical Characteristics

General description (for patients): 

Decreased pigmentation with severe mental and physical retardation is the hallmark of this rare disorder. The hair, including eyelashes and eyebrows are white from birth. The corneas of the eye are “cloudy” and opacification merges with the sclera; there may be other ocular signs but internal examination is impossible due to the lack of corneal clarity. The skin is pale but may have a yellowish tinge and there may be a few dark pigment spots. Within several months it is evident that development is retarded and all responses remain infantile. Spontaneous writhing movements are noted early and never disappear. The eyes do not respond to light. There is an exaggerated startle response but children often respond to handling with smiles. The arms and legs become stiff and have brisk reflexes.  

Medical description: 

This is a rare disorder of pigmentation and severe developmental retardation. There is also corneal scleralization and blindness although internal ocular structures have not been visualized.  Spasticity of the extremities and athetoid movements are evident at several months of age.  The hair including lashes is white with a yellowish tinge and occasional dark strands.  The skin likewise has a slight yellowish tinge suggesting tyrosinase positive albinism but no relevant studies have been done.   No normal milestones are attained, and all neurological responses remain infantile. Some sensory responses such as withdrawal from painful stimuli are present. Deep tendon reflexes are brisk probably from birth and flexion contractures eventually develop. Extensor plantar responses are present. Some hyperirritability is often noted and the startle response is exaggerated but no seizures have been reported.

Genetics: 

The majority of reported cases have been familial and born of consanguineous unions suggesting autosomal recessive inheritance. No metabolic abnormalities have been found and the mutation remains unknown.  However, a locus on chromosome 3 has been identified.  A single Mennonite family with four affected offspring born of a consanguineous marriage has been reported.  The parents had Amish ancestry.

Treatment:

 There is no known treatment.

Prognosis: 

Poor. No reported cases have developed beyond the infantile stage. They may live at least to adolescence.

Ancillary tr:eatments and support:

Custodial and supportive care is necessary.

Specialists and specialty centers:

pediatrician, neurologist, nutritionist.

References:

Chabchoub E, Cogulu O, Durmaz B, Vermeesch JR, Ozkinay F, Fryns JP. Oculocerebral Hypopigmentation Syndrome Maps to Chromosome 3q27.1q29. Dermatology. 2012 Feb 7. [Epub ahead of print] PubMed PMID: 22327602.

Cross, H.E., McKusick, V.A., and Breen, W.:  A new oculocerebral syndrome with hypopigmentation.  J. Pediat. 70: 398-406, 1967.  PubMed ID: 4959856

Fryns, J.P., Dereymaeker, A.M., Heremans, G., Marien, J., van Hauwaert, J., Turner, G., Hockey, A., and van den Berghe, H.: Oculocerebral syndrome with hypopigmentation (Cross syndrome): report of two siblings born to consanguineous parents.  Clin. Genet. 34: 81-84, 1988.  PubMed ID: 3191612

Tezcan, I., Demir, E., Asan, E., Kale, G., Muftuoglu, S.F., and Kotiloglu, E.:  A new case of oculocerebral hypopigmentation syndrome (Cross syndrome) with additional findings.  Clin. Genet. 51: 118-121, 1997.  PubMed ID: 9112000

Resources:

National Organization for Albinism