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Table 1 Clinical presentation and diagnostic characterization of individuals with pathogenic POMK mutations

From: Further evidence for POMK as candidate gene for WWS with meningoencephalocele

  this study Di Constanzo et al. [5], Renesse et al. [10], Jae et al. [11], Preiksaitiene et al. [12], Ardicli et al. [13], Strang-Karlsson et al. [7],
family 1
patient 1#
family 1
patient 2#
family 2
patient 3
family 2
patient 4
family 3
patient 5*
family 4
patient 6*
family 4
patient 7*
family 5
patient 8*
family 5
patient 9#
family 6
patient 10*
family 6
patient 11*
family 6
patient 12*
family 7
patient 13*
family 8
patient 14
family 9
patient 15
family 9
patient 16
c-DNA mutation c.640C>T c.640C>T c.325C>T c.325C>T c.286delT
c.325C>T c.325C>T c.410T>G
c.136C>T c.136C >T c.136C>T c.136C>T c.401T>G c.965C>T
protein mutation p.Gln214* p.Gln214* p.Gln109* p.Gln109* p.Phe96Phefs*19
p.Gln109* p.Gln109* p.Leu13Arg
p.Arg46Ter p.Arg46Ter p.Arg46Ter p.Arg46Ter p.V134G p.Pro322Leu
age of onset neonatal neonatal infancy infancy neonatal infancy neonatal neonatal neonatal neonatal neonatal neonatal neonatal childhood childhood childhood
first signs in utero: cerebral malformation, opened dorsal 4th ventricle, encephalocele in utero: cerebral malformation, agyri, encephalocele floppiness and delayed walking at 18 months floppiness and delayed walking at 18 months in utero: macrocephaly, hydrocephalus feeding problems, motoric development delayed proximal weakness, little antigravity movements, hyporeflexia typical WWS in utero:
ventriculomegaly/ hydrocephalus, absence of the falx cerebri and cerebellar tentorium, occipital encephalocele
in utero: ventriculo-megaly, thin cortex, hydro-cephalus, macro-cephaly in utero: ventriculo-megaly in utero: ventriculo-megaly (lateral / 4th ventricle) in utero: hydrocephalus, ventriculo-megaly, suspected aplasia of cerebellar vermis muscle weakness, easy fatigue, clumsiness, difficulty running and climbing hip / neck cramps, growing pain thigh stiffness, cramps thigh/neck
muscle weakness (locali-sation) CMD, postnatal reduced spontaneous motor movement, lifting limbs against gravity CMD, postnatal reduced spontaneous motor movement, lifting arms against gravity proximal weakness, calf pseudo-hypertrophy, mild facial weakness posture and gait affected CMD, spontaneous motility absent at 7 months CMD, proximal weakness (difficulties climbing stairs and running) proximal weakness, never able to sit, roll on the side with 2 years typical WWS n/a n/a n/a n/a n/a CMD, muscle weakness age of 12), calf hypertrophy, proximal muscle weakness, Gowers sign CMD, proximal weakness, calf hyper-trophy CMD, proximal weakness
CK level 7159 U/l 8769 U/l 1090 U/l 1420 U/l 3985 U/l 1238 U/l 1810 U/l typical WWS n/a n/a n/a n/a n/a 2400 U/l 1000-4000 U/l 6800 U/l
biopsy findings n/a n/a n/a dystrophic, cell death and regeneration positive for all markers tested dystrophin, utrophin, merosin, dysferlin, sarco-glycans and b-dystro-glycan muscle fibers are absent myopathic pattern with normal dystrophin expression (9 months) re-biopsy (age of 4): laminin, alpha 2, merosin reduced myopathic pattern and merosin deficiency n/a n/a n/a n/a n/a n/a mild dystrophic changes, increase in nuclei, degenerating and regenerating fibers, focal endomysal fibrosis immunofluorescent analysis: laminin alpha 2 pos., alpha-dystroglycan neg., dystrophin/ sarcoglycan pos. normal moderate chronic myopathic changes, small groups of regenerating fibers, sparse inflammatory cell infiltrates, alpha-dystroglycan deficiency, normal merosin immunolabelling
MRI findings meningocele, opened 4th ventricle, hypoplastic vermis cerebellum, small myelon, arachnoid cyst meningocele, opened 4th ventricle, hypoplastic vermis, lissencephaly, small myelon, arachnoid cyst cysterna magna temporal lobe arachnoid cyst cobblestone lissencephaly, agenesis of the corpus, severe cerebellar vermis hypoplasia symmetric cerebral white matter changes (15 months) hypomyelination aquaeductal stenosis, hydrocephalus, agyria, cerebellar and brainstem hypoplasia, Arnold-Chiari malformation n/a n/a n/a n/a n/a cerebellar hypoplasia, cortical disorganization, brainstem hypoplasia, cerebellar cortical microcysts, bilateral hippocampal incomplete rotation n/a n/a
ocular findings anophthalmus (right eye), blindness, cataract (left), staphyloma (left) congenital cataract, bilateral hypoplastic corpus vitreum, lagophthalmos bilateral none none glaucoma (right eye), bilateral retinal degeneration eyes appeared large (corneal diameter 11,5 mm) – no criteria for megalo-cornea reduced visual acuity micro-ophthalmia, persistent hyperplasic primary vitreous body, myopia, cataract cataract, coloboma none none none none none none none
additional information pathological EEG with delta-waves, tonic-clonic seizures, bilateral sensorineural hearing loss pathological EEG with multifocal pathological EEG-potentials, seizures, bilateral sensorineural hearing loss, patent foramen ovale hyporeflexia   hypotonia, bilateral sensorineural hearing loss,delayed psycho-motor development, tonic seizures sensorineural hearing loss BERA: moderate hearing impairment, contractures knees/hips        mirror movements (hands) since infancy birth asphyxia due to placental abruption, high frequency hearing loss preterm birth (placenta previa) Weakened function of left ventricle (age 12)
latest check up 30 months: severe motor and verbal developmental disorder: hypersalivation, no movement of the head, no active movement of the extremities or active language 17 months: cardiopulmonary resuscitation with exitus letalis due to an aspiration still ambulatory at 25 at the age of 13 years: climbs stairs without support death at the age of 4 years at the age of 17 years: wheelchair, at the age of 21 years: lost ambulation, not able to stand, eat or drink without support at the age of 10 years: scoliosis, pathologic pulmonary function (VC:36%) death at the age of 3 years TOP (19 weeks of gestation) died during labor (32 weeks of gestation, TOP) TOP (16 weeks of gestation) TOP (14/15 weeks of gestation) TOP (19 weeks and 6 days of gestation)
autopsy: massive hydrocephalus, aplasia of the cerebellar vermis
at the age of 19 years: mild learning difficulties, reduced deep tendon reflexes, pes cavus deformity calf hypertrophy, mild lumbar lordosis, slightly winged scapulae, brisk tendon reflexes in upper extremities calf hypertrophy, mild lumbar lordosis, slightly winged scapulae, brisk tendon reflexes in upper extremities, problems walking on heels
  1. Columns of individuals with severe WWS phenotype are marked *; #: WWS+ encephalocele