TABLE 1.
HPMRS phenotype overview, listed by subtypes (HPMRS 1–6)
| HPMRS type | 1 | 2 | 3 | 4 | 5 | 6 |
|---|---|---|---|---|---|---|
| Gene | PIGV 7 , 23 , 24 , 25 | PIGO 2 , 4 , 5 , 9 , 10 , 17 , 26 , 27 , 28 | PGAP2 8 , 12 , 14 , 15 , 16 | PGAP3 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 | PIGW 6 , 39 , 40 | PIGY 41 |
| Inheritance | AR | AR | AR | AR | AR | AR |
| Growth | normal | NA – data limited | normal | normal | normal – few data reported | abnormal – poor growth |
| Signs and Symptoms | ||||||
| Neurology | ||||||
| Intellectual disability | + | ++ | ++ | ++ | ++ | ++ |
| Developmental delay | ++ | ++ | ++ | ++ | ++ | ++ |
| Hypotonia | + | ++ | + | ++ | ++ | − |
| Seizures/epilepsy | + | ++ | ++ | ++ | ++ | + |
| Neurosensorial | ||||||
| Hearing impairment | +/− | + | + | + | − | − |
| Vision impairment | NA | NA | + | NA | NA | + (congenital cataract, strabism) |
| Cardiological abnormalities | +/− | +/− | +/− | + | − | − |
| Gastrointestinal/anorectal abnormalities | + (Hirschprung, anterior anus, abdominal distension) | + (anal stenosis, anal atresia, mild anal prolapse, inguinal hernia) | +/− | +/− (inguinal hernia, constipation) | − | +/− (poor feeding, abdominal distension, NEC) |
| Vescicouretral anomalies | + | +/−(hypogenitalism) | − | +/− | − | +/− |
| Endocrine dysfunction | − | − | precocious adrenarche | − | − | − |
| Facial dysmorphism | ||||||
| Broad nasal bridge | ++ | +/− | +/− | ++ | + | − |
| Tented up lips | ++ | + | +/− | ++ | + | − |
| Hypertelorism | ++ | +/− | +/− | ++ | − | +/− |
| Wide palpebral fissures | +/− | |||||
| Cleft palate | + | + | +/− | ++ | − | − |
| Abnormalities of extremities | ++ (brachytelephalangyhypoplastic finger and toenails, hypoplastic distal phalange) | ++ (brachytelephalangyhypoplastic finger and toenails, hypoplastic distal phalange) | +/− | +/− | − | + (brachytelephalangy) |
| Investigations | ||||||
| ALP | ++ | ++ | + | ++ | + | + |
| Brain imaging | Mostly normal ‐ one reported poorly formed cerebellar vermis | Abnormal – hypoplasia of cerebellar vermis and brainstem, hypomyelination and abnormal T1 and T2 signal in basal ganglia to brainstem, increased DWI signal in globus pallidus and dorsal brainstem, signs of cerebral atrophy | Mostly normal – signs of cerebral atrophy, hypoplasia of the corpus callosum reported, Dandy Walker malformation | Abnormal – thin corpus callosum, hypoplasia of cerebellar vermis, dilated ventricles, brain atrophy, fronto‐parietal atrophy, mega cisterna magna, small capsula interna, Dandy‐Walker variant | Abnormal ‐ widened subarachnoid space | Abnormal ‐ white matter loss |
| CSF study | NA | NA | pyridoxine 8 mmol/L (ref. 10–37); 5MTHF 66 mmol/L (ref. 72–172) | NA | Investigated for infection, no Neurotransmitter done | NA |