Table 1.
An Overview of the Affected Individuals’ Symptoms and a Comparison with the Different Aspects of the Already Identified IGDs
|
Clinical Syndrome |
||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MCAHS2 | Ohtahara Syndrome | HPMRS6 | CHIME Syndrome | HPMRS5 | Inherited GPI Deficiency | HPMRS1 | MCAHS1 | HPMRS2 | IGD Identified in This Study | MCAHS3 | MRT42 | HPMRS4 | HPMRS3 | |||
| MIM no. | 300868 | 3008350 | 616809 | 280000 | 616025 | 610293 | 239300 | 614080 | 614749 | NA | 615398 | 611655 | 615716 | 614207 | ||
| Associated gene (MIM no.) | PIGA (311770) | PIGQ (605754) | PIGY (610662) | PIGL (605947) | PIGW (610275) | PIGM (610273) | PIGV (610274) | PIGN (606097) | PIGO (614730) | PIGG (not assigned) | PIGT (610272) | PGAP1 (611655) | PGAP3 (611801) | PGAP2 (615187) | ||
| GPI-biosynthesis stepa | GPI biosynthesis (ER cytoplasmic side) | GPI biosynthesis (ER lumen side) | GPI transamidase component (ER) | removal of inositol-linked acyl chain (ER) | lipid remodeling in Golgi | |||||||||||
| step 1 | step 1 | step 1 | step 2 | step 4 | step 6 | step 7 | step 8 | step 10 | step 11 | step 12 | step 13 | step 16 | step 17 | |||
| No. of families (affected individuals) | 9 (13) | 1 (1) | 2 (4) | 6 (7) | 1 (1) | 2 (3) | 14 (20) | 9 (17) | 4 (6) | 1 (EG01 and EG002) | 1 (JP01) | 1 (PK01 and PK02) | 3 (7) | 5 (7) | 4 (6) | 4 (9) |
| Mode of inheritance (locus) | X-linked (Xp22.2) | AR (16p13.3) | AR (4q22.1) | AR (17p11.2) | AR (17q12) | AR (1q23.2) | AR (1p36.11) | AR (18q21.33) | AR (9p13.3) | AR (4p16.3) | AR (4p16.3) | AR (4p16.3) | AR (20q13.12) | AR (2q33.1) | AR (17q12) | AR (11p15.4) |
| Clinical Features | ||||||||||||||||
| DD or ID | + | + | +/− | + | + | + | + | + | +/− | + | + | + | + | + | + | + |
| Seizures | + (<1 year) | + (<1 year) | +/− | + (<1 year) | + (<1 year) | + | + | + (<1 year) | + | + (4 months) | + (10 months) | +/− | + (<1 year) | +/− | +/− | +/− |
| Hypotonia | + | + | +/− | + | + | − | + | + | + | + | + | + | + | + | + | + |
| Head circumference | ND | ND | − or microcephaly | ND | ND | ND | ND | − or microcephaly | − or microcephaly | ND | ND | ND | − or microcephaly | − or microcephaly | − or microcephaly | ND |
| Facial dysmorphism | +/− | NA | + | + | + | − | + | + | + | + | − | − | + | − | + | +/− |
| Hearing impairment | + | NA | − | + | − | − | +/− | − | +/− | − | − | − | +/− | − | − | +/− |
| Joint contractures | + | + | +/− | ND | ND | ND | ND | ND | ND | hyperlaxity | − | − | ND | ND | ND | ND |
| Skeletal anomalies | ND | ND | short fingers and small feet, proximal limb shortening, hip dysplasia | ND | ND | ND | hypoplastic terminal phalanges | ND | hypoplastic terminal phalanges | − | − | − | osteopenia, scoliosis delayed bone age, short arms | ND | ND | ND |
| Skin anomalies | +/− | − | − | +/− | − | − | − | − | − | − | − | − | − | − | − | − |
| Congenital heart defects | +/− | − | − | +/− | − | − | +/− | +/− | +/− | − | − | − | +/− | − | − | +/− |
| Vesicoureteral reflex or anomalies in urinary tract | +/− | − | +/− | +/− | − | − | +/− | +/− | − | − | − | − | +/− | − | − | − |
| Anorectal anomalies | − | − | − | − | − | − | +/− | +/− | +/− | − | − | − | +/− | − | − | +/− |
| CNS abnormalities in MRI | +/− | + | +/− | +/− | + | − | + | +/− | +/− | thin corpus callosum | − | cerebellar hypoplasia, cerebral atrophy | + | +/− | +/− | +/− |
| Increased serum alkaline phosphatase | +/− (mild) | − | +/− (mild) | +/− | + | − | + | − | + | − | − | NA | − (hypophosphatasia) | − | + | + |
| Decreased GPI-AP | + | NA | + | + | + | + | + | + | + | − | − | − | + | − | +/− | + |
Abbreviations are as follows: +, present; −, absent; +/−, variable; AR, autosomal recessive; MCAHS, multiple congenital anomalies-hypotonia-seizures syndrome; CHIME, colobomas, congenital heart disease, ichthyosiform dermatosis, mental retardation, and ear anomalies; HPMRS, hyperphosphatasia with mental retardation syndrome; MRT42, mental retardation, autosomal recessive 42; DD, development delay; ID, intellectual disability; NA, not applicable; and ND, not determined.
a
Based on the review by Kinoshita.6