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.905T>A | c.325C>T | c.325C>T | c.410T>G c.773A>G | c.410T>G c.773A>G | c.136C>T | c.136C >T | c.136C>T | c.136C>T | c.401T>G | c.965C>T c.136C>T | c.965C>T c.136C>T |
protein mutation | p.Gln214* | p.Gln214* | p.Gln109* | p.Gln109* | p.Phe96Phefs*19 p.Val302Asp | p.Gln109* | p.Gln109* | p.Leu13Arg p.258Arg | p.Leu13Arg p.258Arg | p.Arg46Ter | p.Arg46Ter | p.Arg46Ter | p.Arg46Ter | p.V134G | p.Pro322Leu p.Arg46Ter | p.Pro322Leu p.Arg46Ter |
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 |