| Domain | Summary | Evidence strength | Key citations |
|---|---|---|---|
| Identity / identifiers | **Disease:** short-rib thoracic dysplasia 21 without polydactyly (SRTD21), a **Mendelian skeletal ciliopathy** associated with **biallelic KIAA0753** variants. **Gene/protein aliases:** KIAA0753, **MOONRAKER (MNR)**, **OFIP**. **MONDO:** MONDO:0030356. **OMIM caution:** available evidence clearly supports **KIAA0753 as the causal gene** and a broader KIAA0753-related ciliopathy spectrum; disease/gene OMIM distinctions should be checked in OMIM directly rather than inferred here. | Strong for disease-gene identity; moderate for exact cross-database identifier harmonization | (pqac-00000014, pqac-00000015, pqac-00000016, pqac-00000029) |
| Inheritance | **Autosomal recessive**; reported affected individuals carry **biallelic** variants (homozygous or compound heterozygous). Several skeletal cases occurred in **consanguineous** families, but non-consanguineous families are also reported. | Strong | (pqac-00000013, pqac-00000015, pqac-00000034, pqac-00000038) |
| Core phenotype | Congenital/prenatal **narrow thorax**, **short ribs**, **short limbs/short tubular bones**, **brachydactyly**, abnormal pelvis including **trident acetabula/ilia**, neonatal or infantile **respiratory distress**, severe short stature, and variable developmental delay/hypotonia. **Polydactyly is absent in the canonical SRTD21 designation**, although some broader KIAA0753-spectrum cases reported in later literature show overlap with other ciliopathy phenotypes. | Strong for skeletal-respiratory core; moderate for full spectrum boundaries | (pqac-00000014, pqac-00000015, pqac-00000034, pqac-00000035, pqac-00000040) |
| Variants | Recurrently reported skeletal-dysplasia variants are mostly **predicted loss-of-function/truncating** alleles, including **c.970C>T (p.Arg324\*)**, **c.943C>T (p.Gln315\*)**, and **c.1271del (p.Pro424Hisfs\*9)**; one family in a later skeletal ciliopathy cohort had **c.810C>T (synonymous, splice-affecting candidate)**. Reported gnomAD frequencies for some KIAA0753 ciliopathy alleles are extremely low, and homozygotes were not observed in cited reports. | Strong for recurrent truncating skeletal alleles; moderate for complete variant catalog | (pqac-00000015, pqac-00000020, pqac-00000034, pqac-00000038) |
| Mechanism / pathophysiology | KIAA0753/MNR is a **centrosome/pericentriolar satellite and distal centriole protein** required for **primary ciliogenesis**. It functions with **OFD1, FOPNL, and CEP90** in a distal centriole module that helps establish **distal appendages**, recruit **CEP83**, support **preciliary vesicle docking**, and regulate **centriole length**. Loss impairs ciliation and downstream **SHH** and some **WNT** signaling; growth-plate and cerebellar developmental defects are consistent downstream consequences. | Strong | (pqac-00000016, pqac-00000021, pqac-00000022, pqac-00000027, pqac-00000029, pqac-00000030, pqac-00000031) |
| Diagnosis | Real-world diagnosis has relied on **prenatal ultrasound**, **fetal MRI/brain MRI**, **skeletal survey/radiographs**, and **exome or genome sequencing**. Suggestive imaging includes short femurs/limbs, narrow thorax, trident pelvis, metaphyseal changes, and in some allelic-spectrum cases **molar tooth sign** or other CNS anomalies. Functional follow-up in research settings has used patient fibroblasts, RNA/cDNA studies, and variant rescue assays. | Strong for sequencing + imaging; moderate for functional assays as clinical tools | (pqac-00000013, pqac-00000014, pqac-00000019, pqac-00000021, pqac-00000038) |
| Prognosis | **Highly variable.** Reported outcomes range from **fetal loss/neonatal death** or death in childhood from **respiratory failure/pulmonary complications** to survival into childhood with chronic respiratory disease, growth failure, hypotonia, developmental delay, and ongoing support needs. Long-term natural history, life expectancy, and population survival statistics are **not established**. | Moderate for variability; weak for long-term statistics | (pqac-00000014, pqac-00000015, pqac-00000020, pqac-00000034, pqac-00000036) |
| Treatment / management | **No disease-specific or disease-modifying therapy established.** Management is supportive and multidisciplinary: neonatal/childhood **respiratory support** (e.g., tracheostomy, ventilation, CPAP), **feeding support** including tube feeding/gastrostomy, developmental therapies, and surveillance for renal/hepatic/neurologic complications as indicated by phenotype. No relevant interventional clinical trial was identified in the cited evidence. | Moderate for supportive care; weak for formal guidelines | (pqac-00000014, pqac-00000015) |
| Prevention / screening | **No primary prevention** known for the disease biology. For at-risk families, prevention is mainly **genetic counseling**, **carrier testing**, **prenatal diagnosis** by targeted familial-variant testing or exome/genome sequencing, and potentially **preimplantation genetic testing** if the familial variants are known. Population screening recommendations are **not established**. | Moderate | (pqac-00000013, pqac-00000014, pqac-00000038) |
| Models / comparative evidence | Experimental systems include **patient fibroblasts**, **NIH3T3 and RPE1 KIAA0753/MNR loss-of-function cells**, **mouse embryos** lacking **Mnr** with defective ciliogenesis/Hedgehog-linked development, **zebrafish kiaa0753 nonsense mutants** with curved body and altered cartilage patterning, and **Paramecium/mammalian comparative ciliogenesis studies** for conserved distal appendage assembly. A naturally occurring veterinary KIAA0753 disease homolog is **not established**. | Strong for engineered models; weak for natural animal disease | (pqac-00000021, pqac-00000029, pqac-00000031, pqac-00000034, pqac-00000035) |
| Unknown / not established | Population **prevalence**, **incidence**, **carrier frequency**, penetrance estimates, validated **modifier genes**, environmental risk/protective factors, biomarker-based monitoring, and disease-specific pharmacologic/gene/RNA/cell therapies are **not established** in the cited evidence. | Strong for absence of established evidence | (pqac-00000014, pqac-00000016, pqac-00000038) |


*Table: This table provides a compact knowledge-base style summary of SRTD21 caused by biallelic KIAA0753 variants, covering identity, phenotype, mechanism, diagnosis, prognosis, management, prevention, and model systems. It also flags where evidence is strong versus where key aspects remain not established.*