Pathogenic homozygous variant in POMK gene is the cause of prenatally detected severe ventriculomegaly in two Lithuanian families

Am J Med Genet A. 2020 Mar;182(3):536-542. doi: 10.1002/ajmg.a.61453. Epub 2019 Dec 12.


Biallelic pathogenic variants in POMK gene are associated with two types of dystroglycanopathies: limb-girdle muscular dystrophy-dystroglycanopathy, type C12 (MDDGC12), and congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A12 (MDDGA12). These disorders are very rare and have been previously reported in 10 affected individuals. We present two unrelated Lithuanian families with prenatally detected hydrocephalus due to a homozygous nonsense variant in the POMK. The first signs of hydrocephalus in the affected fetuses became evident at 15 weeks of gestation and rapidly progressed, thus these clinical features are compatible with a diagnosis of MDDGA12. The association between pathogenic POMK variants and macrocephaly and severe hydrocephalus has been previously reported only in two families. Clinical and molecular findings presented in this report highlight congenital hydrocephalus as a distinct feature of POMK related disorders and a differentiator from other dystroglycanopathies. These findings further extend the spectrum of MDDGA12 syndrome.

Keywords: POMK; Walker-Warburg syndrome; hydrocephalus; muscular dystrophy-dystroglycanopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / pathology
  • Codon, Nonsense / genetics
  • Female
  • Homozygote
  • Humans
  • Infant, Newborn
  • Male
  • Muscular Dystrophies, Limb-Girdle / diagnosis*
  • Muscular Dystrophies, Limb-Girdle / diagnostic imaging
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / pathology
  • Mutation / genetics
  • Nervous System Malformations / diagnosis*
  • Nervous System Malformations / diagnostic imaging
  • Nervous System Malformations / genetics
  • Nervous System Malformations / pathology
  • Pedigree
  • Pregnancy
  • Protein Kinases / genetics*
  • Ultrasonography, Prenatal


  • Codon, Nonsense
  • POMK protein, human
  • Protein Kinases