Amish, Mennonite, and Hutterite
Genetic Disorder Database

Polyhydramnios, megalencephaly and symptomatic epilepsy

Disorder
OMIM #: #611087  (Click to access OMIM database)
Disorder: Polyhydramnios, megalencephaly and symptomatic epilepsy 
Also known as: PMSE syndrome
Pretzel syndrome
STRADA deficiency 
Clinical
Phenotype: polyhydramnios, feeding difficulties, macrocephaly, hypotonia, long face, large forehead, peaked eyebrows, broad nasal bridge, hypertelorism, large mouth with thick lips, frontal bossing in childhood, seizures, developmental delay, motor delay, ventriculomegaly, congenital heart defect 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks:

Testing is available at LHSC.

Autosomal recessive  

Mutations
1   Old Order Mennonite  
Gene: STRADA (LYK5)
Base Change: 7304bp deletion: exons 9-13
Amino Acid Change:
Last updated: 2022-11-15 

References
Dang LT, Glanowska KM, Iffland PH, Barnes AE, Baybis M, Liu Y, Patino G, Vaid S, Streicher AM, Parker WE, Kim S, Moon UY, Henry FE, Murphy GG, Sutton M, Parent JM, Crino PB. (2020) Multimodal Analysis of STRADA Function in Brain Development. Front Cell Neurosci May 8;14:122.
PubMed ID: 32457579 
Hutson J, Siu VM, Rupar CA. (2022) Clinical Conundrum: Polyhydramnios as a Marker for a Fetal Genetic Syndrome in the Canadian Old Order Mennonite Population. J Obstet Gynaecol Can Jul;44(7):798-802.
PubMed ID: 35131504 
Parker WE, Orlova KA, Parker WH, Birnbaum JF, Krymskaya VP, Goncharov DA, Baybis M, Helfferich J, Okochi K, Strauss KA, Crino PB. (2013) Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder. Sci Transl Med Apr 24;5(182):182ra53.
PubMed ID: 23616120 
Puffenberger EG, Strauss KA, Ramsey KE, Craig DW, Stephan DA, Robinson DL, Hendrickson CL, Gottlieb S, Ramsay DA, Siu VM, Heuer GG, Crino PB, Morton DH. (2007) Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5. Brain 130(Pt 7): 1929-1941.
PubMed ID: 17522105 

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