Table 3 Possible diagnostic clues in patients with POMT1-related disorders

A good clinical characterization remains a mandatory prerequisite greatly improving the diagnostic strategy and ultimately shortening the diagnostic yield and time to report.

WWS should be prenatally considered in the presence of fetal ultrasound abnormalities with ventricular dilatation in combination with infratentorial and/or ocular anomalies[32].

Diagnosis of an occipital encephalocele might be a diagnostic clue for POMT1 as causative gene within the different genes associated with WWS.

In the European population POMT1 is the gene most commonly associated with WWS ([18], personal data).

In patients with a complex brain malformation not suggestive for a specific monogenic disorder early CK analysis as a simple laboratory test could potentially guide the diagnosis of a dystroglycanopathy.

In patients with unexplained cognitive impairment, microcephaly and muscular weakness early CK analysis may also help to identify milder clinical manifestations of dystroglycanopathy.

A dystroglycanopathy should also be considered in any CMD or LGMD patients, negative for Duchenne or Becker muscular dystrophy, with cognitive impairment with or without structural brain malformations, prompting genetic analysis of a NGS panel including POMT1 prior to muscle biopsy.