| Subtype | Umbrella/subtype MONDO where evidenced | Causal gene | Inheritance | Molecular role | Hallmark human phenotype / counts from 337-case systematic review | Representative variants | Diagnostic functional assay |
|---|---|---|---|---|---|---|---|
| MCAHS (umbrella) | MONDO:0100247 umbrella evidenced; subtype MONDOs only partly evidenced in gathered data (pqac-00000000) | PIGN, PIGA, PIGT (pqac-00000000) | Mixed by subtype: AR for PIGN and PIGT; X-linked for PIGA germline disease context; umbrella-level inheritance NR (pqac-00000001, pqac-00000002) | Inherited GPI-anchor biosynthesis defects causing reduced/abnormal GPI-anchored proteins on cell surfaces (pqac-00000010) | Severe neurodevelopmental disease with seizures, hypotonia, developmental delay/intellectual disability; review states MCAHS caused by PIGA/PIGN/PIGT is among the more severe GPIBD phenotypes (pqac-00000002) | NR at umbrella level | Flow-cytometric assessment of GPI-anchored proteins / FLAER-based assays in blood cells or fibroblasts are used across GPI deficiencies (pqac-00000004, pqac-00000010) |
| MCAHS1 | MONDO:0013563 evidenced for “multiple congenital anomalies-hypotonia-seizures syndrome 1” (pqac-00000000) | PIGN (pqac-00000000) | Autosomal recessive (inherited GPI deficiency context; biallelic disease) (pqac-00000000) | PIGN mediates ethanolamine phosphate transfer during GPI-anchor biosynthesis in the ER (pqac-00000010) | PIGN cases in review: n=27; seizures 23; delayed motor development 7; developmental delay/intellectual disability 23; hypotonia 22 (pqac-00000002) | Specific PIGN variants NR in gathered evidence | Reduced GPI-anchored protein expression by flow cytometry is the relevant functional assay class for GPIBD; subtype-specific PIGN assay details NR in gathered evidence (pqac-00000010) |
| MCAHS2 | Umbrella MONDO:0100247 evidenced; subtype-specific MONDO for MCAHS2 NR in gathered evidence (pqac-00000000) | PIGA (pqac-00000000) | X-linked (germline PIGA disease context) (pqac-00000000, pqac-00000002) | PIGA is part of the GPI-N-acetylglucosaminyltransferase complex catalyzing the first step of GPI-anchor biosynthesis in the ER (pqac-00000010) | PIGA cases in review: n=81; seizures 76; delayed motor development 61; developmental delay/intellectual disability 70; hypotonia 55; cerebellar atrophy 19 (pqac-00000002) | Specific PIGA variants NR in gathered evidence | Flow cytometry of GPI-anchored proteins / granulocyte CD16b-type screening is relevant for GPI deficiencies; subtype-specific PIGA functional assay details NR in gathered evidence (pqac-00000010) |
| MCAHS3 | Umbrella MONDO:0100247 evidenced; subtype-specific MONDO for MCAHS3 NR in gathered evidence (pqac-00000000) | PIGT (pqac-00000000, pqac-00000001) | Autosomal recessive; affected siblings with compound heterozygous variants reported (pqac-00000001) | PIGT encodes a subunit of the heteropentameric GPI transamidase complex that attaches GPI anchors to proteins (pqac-00000001, pqac-00000010) | PIGT cases in review: n=38; seizures 33; delayed motor development 31; developmental delay/intellectual disability 34; hypotonia 17; cerebellar atrophy 15 (pqac-00000002) | c.918dupC (frameshift), c.1342C>T (missense) (pqac-00000001) | Flow cytometry showing decreased surface expression of GPI-anchored proteins on granulocytes; proposed screening approach because standard CDT/N-glycan CDG screens may miss PIGT-CDG (pqac-00000001, pqac-00000009) |


*Table: This table summarizes the MCAHS umbrella disorder and its key molecular subtypes using only gathered evidence. It highlights subtype-specific genes, inheritance, molecular function, systematic-review phenotype counts, representative variants where available, and the main functional diagnostic assays.*