MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: LYK5

PMSE syndrome
Megalencephaly
Epilepsy syndrome

Polyhydramnios
Prematurity
Seizures
Epilepsy
Microcephaly
Phychomotor retardation
Congenital heart defects
Diabetes insipides

LYK5 Deficiency

Clinical Characteristics

General description (for patients): 

This is an unusual seizure syndrome associated with excess amniotic fluid and mild prematurity. Heart defects are common, mostly involving holes in the atral septum.  Regulation of body fluids can be faulty leading to dehydration. Seizures begin between 3 and 7 months in all patients and can be severe.  Only 16 cases have been reported, and many do not live beyond early childhood.

Medical description:  

Sixteen cases with severe, early onset seizures have been reported with the unusual association of polyhydramnios, psychomotor retardation and death in childhood.  Twenty-five per cent have atrial septal defects. Diabetes insipidus was found in two and autopsy in one patient revealed extensive malformations, both gross and histological.  Facial dysmorphology is present at birth with progression to a rather characteristic facial elongation, thickening of the lips and hypertelorism.

Genetics:

LYK5 deficiency seems to be caused by a defect in the LYK5 gene located on chromosome  7 (17q23.3).  The condition has only been reported in Old Order Mennonite families in whom a large (7304 base pairs) homozygous deletion was present in 16 patients.

Treatment:

No treatment is available.

Prognosis:

Poor. Most patients are confined to a wheelchair and have generalized delays in their neurodevelopment.  They can live into adulthood.

Ancillary treatments and support:

General supportive care.

Specialists and specialty centers:

Pediatrician, neurologist.

References:

Puffenberger, E.G., Strauss, K.A., Ramsey, K.E., Craig, D.W., Stephan, D.A., Robinson, D.L., Hendrickson, C.L., Gottlieb, S., ramsay, D.A., Siu, V.M., Heur, G.G., Crino, P.B., and Morton, D.H.:  Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5.  Brain 130: 1929-1941, 2007.  PubMed ID: 17522105