| Subtype | OMIM disease ID | Gene | Molecular role / mechanism | Hallmark distinguishing findings | Lethality / survival | Key evidence / date |
|---|---:|---|---|---|---|---|
| LCCS1 | 253310 | GLE1 | Regulates mRNA export and translation; GLE1-related fetal motor neuron disease with anterior horn involvement (pqac-00000000, pqac-00000007) | Complete fetal immobility, severe hydrops, intrauterine growth restriction; flexion contractures, knee hyperextension, pulmonary hypoplasia, micrognathia; fetal death often before 32 weeks (pqac-00000007, pqac-00000012) | Usually prenatal lethal / fetal death before 32 weeks (pqac-00000012, pqac-00000007) | Nousiainen thesis evidence summarized in retrieved text; Trabacca review 2024 (pqac-00000007, pqac-00000012) |
| LCCS2 | not established from retrieved evidence | ERBB3 | Gene assignment supported in review-level retrieved evidence; detailed molecular mechanism not established from primary retrieved text (pqac-00000000, pqac-00000012) | Cranial and ocular abnormalities, enlarged bladder with hydronephrosis, cystic kidney changes (pqac-00000000, pqac-00000012) | Usually fatal shortly after birth (pqac-00000012) | Trabacca review 2024; pediatric motor neuron review evidence in conversation (pqac-00000000, pqac-00000012) |
| LCCS3 | 611369 | PIP5K1C | Phosphatidylinositol-4-phosphate 5-kinase; synthesizes PIP2; reported disease mechanism is haploinsufficiency / truncating loss of function in retrieved evidence (pqac-00000020, pqac-00000021) | Small gestational age, severe multiple joint contractures, muscle atrophy, respiratory failure; detailed fetal findings include talipes equinovarus, extended knees, closed hands/overlapping fingers; possible bilateral dilated lateral ventricles in one fetus (pqac-00000020, pqac-00000021) | Early death due to respiratory failure; prior five reported individuals all died in summarized table, plus two Chinese fetuses described (pqac-00000020, pqac-00000021) | Zhang et al., BMC Pediatrics, 2024; novel c.949_952dup p.S318Ifs*28 plus c.688_689del p.G230Qfs*114 (pqac-00000020, pqac-00000021) |
| LCCS6 | 613915 | ZBTB42 | Not established from retrieved evidence beyond subtype-gene association mention in review evidence (pqac-00000005) | Not established from retrieved evidence | Not established from retrieved evidence | Mentioned in Beecroft review 2018 as LCCS6/ZBTB42 association (pqac-00000005) |
| LCCS7 | inconsistent in retrieved evidence: 616286 vs 607598 | CNTNAP1 | CASPR; essential node of Ranvier component for saltatory conduction; severe axoglial / myelinated axon abnormalities with very low motor nerve conduction velocity (pqac-00000014, pqac-00000008) | Severe arthrogryposis / fetal akinesia with peripheral nerve axoglial defects; marked reduction in motor nerve conduction velocity (<10 m/s) (pqac-00000014) | In review summary, 5 of 7 patients died within 2 months; exact survival spectrum not fully established here (pqac-00000008) | Laquerriere et al., Hum Mol Genet, 2014; Beecroft review 2018 notes OMIM inconsistency in retrieved evidence (pqac-00000014, pqac-00000008) |
| LCCS8 | 616287 | ADCY6 | Adenylyl cyclase type 6; membrane-associated enzyme catalyzing cAMP formation; associated with lack of PNS myelin / hypomyelinating neuropathy in reported cases (pqac-00000022, pqac-00000014) | Distal joint contractures, severe hypotonia, lack of swallowing, absent autonomous respiratory function and deep tendon reflexes; may include hydrocephalus, severe muscle loss, hypomyelinating neuropathy (pqac-00000022) | Original reported siblings died within first 3 months; additional patient died at 36 months after intensive support (pqac-00000022, pqac-00000008) | Agolini et al., Clin Genet, 2020; Laquerriere et al., 2014 discovery paper (pqac-00000022, pqac-00000014) |
| LCCS10 | 617022 | NEK9 | NIMA-related serine/threonine kinase; mitotic spindle / centrosome functions; linked to defective primary cilia formation, with broader cilia/autophagy evidence from NEK9 biology (pqac-00000018, pqac-00000013) | Multiple joint contractures / arthrogryposis; severe cases reported with shortened limbs in literature summaries; neonatal cases included camptodactyly, stiff neck, pyloric stenosis, heart defects (pqac-00000018, pqac-00000019) | Historically described as lethal fetal form, but 2023 report expands to neonatal survivors/discharges; full survival range not established from retrieved evidence (pqac-00000018, pqac-00000019) | Liu et al., Front Genet, 2023; novel variants c.717C>A, c.2824delA, c.61G>T not in ClinVar/HGMD/gnomAD (pqac-00000018, pqac-00000019) |
| LCCS11 | 617194 | GLDN | Gliomedin; required for nodes of Ranvier formation and peripheral nervous system development; GLDN variants disrupt nodal interactions and can be framed as FADS-spectrum nodopathy (pqac-00000011, pqac-00000016) | Hydrops, short long bones, fixed limb joints, absent fetal movements, polyhydramnios, growth restriction, pulmonary hypoplasia, retrognathia; distal arthrogryposis (pqac-00000011) | Not invariably lethal: 4/6 additional patients in 2017 survived beyond neonatal period with intensive chronic respiratory/nutritional support; condition may extend into childhood/adolescence (pqac-00000017, pqac-00000016) | Wambach et al., Hum Mutat, 2017; Potrony et al., J Clin Med, 2022; Mis et al., AJMG A, 2020 (pqac-00000017, pqac-00000011, pqac-00000016) |


*Table: This table summarizes lethal congenital contracture syndrome subtypes supported by evidence retrieved in the conversation. It highlights subtype-gene relationships, distinguishing findings, survival patterns, and places where the evidence base is incomplete or internally inconsistent.*