| Domain | Recommendation | MAXO term suggestion(s) | Evidence/notes |
|---|---|---|---|
| Molecular diagnosis | Perform next-generation sequencing with **WES or broad NGS** as first-line molecular testing when GPS/KAT6B-related disorder is suspected; confirm candidate variants by **Sanger sequencing** and test parents to determine de novo status | MAXO: genetic testing; next-generation sequencing; whole-exome sequencing; Sanger sequencing; familial variant testing | GPS was molecularly solved by WES in the 2012 discovery studies, with Sanger confirmation and parental testing showing de novo heterozygous truncating **KAT6B** variants; later series also used NGS/exome sequencing as routine diagnostics (pqac-00000033, pqac-00000034, pqac-00000037) |
| Variant interpretation | Pay particular attention to **truncating variants in exon 18/C-terminal region** and assess predicted escape from nonsense-mediated decay because this can inform GPS-vs-SBBYSS interpretation | MAXO: sequence variant interpretation; genotype-phenotype correlation assessment | GPS-associated variants often cluster in proximal exon 18 and may escape NMD, producing truncated proteins; careful interpretation is clinically relevant (pqac-00000002, pqac-00000005, pqac-00000037) |
| Prenatal detection | If structural anomalies are seen prenatally, consider **prenatal genetic testing** for KAT6B-related disorder and targeted fetal imaging review | MAXO: prenatal diagnostic testing; prenatal ultrasonography | Prenatal anatomy scan abnormalities were frequent in GPS subsets, and recent case reports describe prenatal detection of corpus callosum/genitourinary/skeletal anomalies before molecular confirmation (pqac-00000026, pqac-00000030) |
| Neuroimaging | Obtain **brain MRI** to evaluate agenesis/hypoplasia of the corpus callosum and other CNS malformations | MAXO: magnetic resonance imaging; neurologic evaluation | Corpus callosum abnormalities are a core GPS feature; postnatal MRI was central to diagnosis in recent GPS cases (pqac-00000022, pqac-00000023, pqac-00000038) |
| Skeletal/orthopedic workup | Perform **skeletal survey and focused knee/limb imaging** to document patellar aplasia/hypoplasia, contractures, clubfoot, hip dysplasia, and other skeletal defects | MAXO: radiographic imaging; skeletal survey; orthopedic evaluation | Patellar abnormalities and flexion deformities are hallmark findings; skeletal survey and radiographs are recommended in case-based literature (pqac-00000022, pqac-00000032, pqac-00000035) |
| Renal/urologic workup | Perform **renal ultrasound / urinary tract imaging** and nephrology-urology assessment to detect hydronephrosis, renal cysts, or structural anomalies | MAXO: renal imaging; nephrology referral; urologic evaluation | Hydronephrosis and renal anomalies are common in GPS; recent neonatal GPS management included surveillance and prophylaxis for hydronephrosis (pqac-00000022, pqac-00000023, pqac-00000030) |
| Cardiac workup | Obtain **baseline ECG and echocardiogram** at diagnosis | MAXO: electrocardiography; echocardiography; cardiology referral | Congenital heart defects are common across KAT6B disorders; Yabumoto et al. recommend baseline ECG/echo, and GPS cohorts show frequent ASD/VSD (pqac-00000022, pqac-00000028, pqac-00000039) |
| Endocrine assessment | Check **thyroid function** (including TSH) early after diagnosis and follow clinically | MAXO: thyroid function test; endocrinology referral | Thyroid abnormalities/hypothyroidism have been reported in KAT6B-related disorders, prompting recommendation for TSH testing soon after diagnosis (pqac-00000028, pqac-00000037, pqac-00000039) |
| Ophthalmology/hearing | Arrange **ophthalmologic** assessment and **hearing evaluation** where clinically indicated | MAXO: ophthalmologic examination; hearing assessment | Ocular and hearing anomalies occur across the spectrum; Yabumoto et al. recommend regular visual assessments and ophthalmology referral (pqac-00000037, pqac-00000039) |
| Feeding/airway evaluation | Assess for **feeding difficulty, aspiration/airway issues, and abnormal breathing**; consider swallow/feeding support and **sleep study** if breathing is abnormal | MAXO: feeding support; sleep study; respiratory evaluation | Feeding difficulties and airway problems such as laryngomalacia/tracheomalacia are recurrent; sleep study is suggested for abnormal breathing (pqac-00000022, pqac-00000023, pqac-00000025, pqac-00000039) |
| Developmental management | Initiate **multidisciplinary developmental care** including physical, occupational, and speech-language therapy | MAXO: physical therapy; occupational therapy; speech therapy; developmental assessment | Severe developmental delay, profound language impairment, hypotonia, and mobility limitations are common and drive supportive therapy needs (pqac-00000016, pqac-00000030, pqac-00000039) |
| Orthopedic intervention | Refer early for **orthopedic management** of clubfoot, contractures, hip dysplasia, and patellar problems; use casting/splinting and surgery as indicated | MAXO: orthopedic management; casting; corrective surgery | Real-world neonatal GPS care included clubfoot casting; contractures and lower-limb malformations are major morbidity drivers (pqac-00000023, pqac-00000030) |
| Surgical management of congenital anomalies | Correct major structural anomalies such as **anal atresia, genital anomalies, airway lesions, cryptorchidism, or selected cardiac defects** when indicated | MAXO: surgical repair; orchiopexy; reconstructive surgery | Recent and prior case reports document successful surgery for anal atresia, laryngomalacia, cryptorchidism, and genital reconstruction in KAT6B-related disorders (pqac-00000023, pqac-00000006, pqac-00000027) |
| Bone health monitoring | Consider **bone densitometry** and fracture surveillance in patients with fractures or low bone health concern | MAXO: bone density assessment; fracture monitoring | Fractures were noted in expanded KAT6B cohorts; Yabumoto et al. recommend bone densitometry when clinically relevant (pqac-00000028, pqac-00000039) |
| Biomarker/advanced diagnostics | **DNA methylation episignature testing** may be useful as an emerging adjunct in unresolved Mendelian neurodevelopmental disorders, but KAT6B-specific routine use remains investigational in the extracted evidence | MAXO: DNA methylation profiling | Recent KAT6B literature cites diagnostic DNA methylation episignature work and clinical epigenomics resources, but no extracted GPS-specific implementation standard was provided (pqac-00000036) |
| Genetic counseling | Provide **genetic counseling** regarding usually **autosomal dominant, de novo** causation, recurrence risk, and family planning; consider prenatal testing in future pregnancies if a familial variant is known | MAXO: genetic counseling; reproductive counseling; prenatal counseling | Most GPS cases arise from de novo heterozygous KAT6B variants; multiple reports emphasize counseling as part of management (pqac-00000001, pqac-00000014, pqac-00000031) |
| Ongoing follow-up | Use a **multidisciplinary longitudinal surveillance** model involving genetics, neurology, orthopedics, cardiology, nephrology/urology, developmental pediatrics, ophthalmology, and other specialties as needed | MAXO: multidisciplinary care; longitudinal monitoring | Recent case reports and cohort studies consistently describe multispecialty follow-up as the practical standard of care because complications are multisystemic and evolve over time (pqac-00000023, pqac-00000032, pqac-00000039) |


*Table: This table summarizes practical diagnostic, monitoring, and supportive-management recommendations for genitopatellar syndrome and related KAT6B disorders, with suggested MAXO-style action labels. It is useful for translating case-series and cohort evidence into structured knowledge-base actions.*