| Category | Summary | Evidence/Citation |
|---|---|---|
| Disease name / synonyms | **Focal dermal hypoplasia (FDH)**; also called **Goltz syndrome** and **Goltz-Gorlin syndrome**. Described as a rare multisystem disorder affecting ectodermal- and mesodermal-derived tissues. | (pqac-00000000, pqac-00000002, pqac-00000005, pqac-00000007) |
| Core molecular cause | Caused by pathogenic variants in **PORCN**, an X-linked gene encoding an ER-resident **membrane-bound O-acyltransferase** required for Wnt ligand acylation/processing and secretion. Loss of PORCN disrupts Wnt signaling during development. | (pqac-00000008, pqac-00000009, pqac-00000012, pqac-00000014) |
| Inheritance / male lethality / mosaicism | **X-linked dominant** inheritance. Most affected individuals are female; most male conceptuses are not viable in utero. Surviving males are often explained by **postzygotic mosaicism**; phenotype variability in females is also influenced by **X-chromosome inactivation**. Rare non-mosaic surviving males have been reported. | (pqac-00000009, pqac-00000010, pqac-00000012, pqac-00000013) |
| Hallmark phenotypes: skin | Characteristic **atrophic linear lesions following Blaschko lines**, pigmentary change, telangiectasias, **fat herniation/yellow nodules**, papillomas, sparse brittle hair/alopecia, and nail dystrophy or agenesis. Histology supports diagnosis with **thinned dermis** and extension of fat into superficial dermis. | (pqac-00000002, pqac-00000016, pqac-00000019, pqac-00000029) |
| Hallmark phenotypes: skeletal / limb | Frequent limb and skeletal anomalies including **syndactyly, polydactyly, ectrodactyly/split hand-foot (lobster-claw), oligodactyly, absent or hypoplastic digits, facial asymmetry, vertebral/long-bone anomalies, short stature**, and reduced bone density/osteoporosis in some reports. | (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000019) |
| Hallmark phenotypes: ocular | Ocular involvement includes **coloboma, microphthalmia, cataract, strabismus, nystagmus, photophobia**, and defects of the iris/retina/choroid/optic nerve; vision loss can occur. | (pqac-00000016, pqac-00000017, pqac-00000019) |
| Hallmark phenotypes: oral / dental | Oral and dental findings include **enamel hypoplasia** (commonly emphasized), microdontia, hypodontia/oligodontia, abnormal roots, taurodontism, delayed/ectopic eruption, cleft lip/palate, high-arched palate, gingival/intraoral papillomas, and gingivitis/caries risk due to enamel defects and hand-function limitations. | (pqac-00000017, pqac-00000020, pqac-00000021, pqac-00000022) |
| Hallmark phenotypes: CNS / other systems | CNS findings are variable: most patients have normal cognition, but **developmental delay/intellectual impairment, epilepsy, microcephaly, thin corpus callosum, hydrocephalus, and hearing loss** have been reported. Other organ systems that may be involved include urinary, gastrointestinal, cardiovascular, endocrine, and thyroid/neoplastic manifestations. | (pqac-00000000, pqac-00000010, pqac-00000017, pqac-00000018, pqac-00000014) |
| Key epidemiologic statistics reported in evidence | Reported figures in available evidence: **~90% female**, **~95% of all cases de novo**, **100% of male cases de novo**, **cognitive impairment ~15%**, and literature/case-based sources note **~300 cases reported** worldwide/in the literature. These are literature-based estimates rather than population incidence/prevalence rates. | (pqac-00000038, pqac-00000000, pqac-00000014) |
| Clinical diagnosis | Diagnosis is primarily **clinical**, based on the characteristic constellation of cutaneous, limb, ocular, and dental findings; some sources reference use of **Bostwick et al. clinical criteria**. Histopathology of skin lesions and skeletal imaging can provide supportive evidence. Differential diagnoses include **incontinentia pigmenti, MIDAS syndrome, EEC syndrome, aplasia cutis congenita, Rothmund-Thomson syndrome**, and others depending on presentation. | (pqac-00000025, pqac-00000028, pqac-00000029, pqac-00000002, pqac-00000003) |
| Genetic / molecular diagnostics | Contemporary molecular confirmation centers on **PORCN testing**. Reported approaches include **PCR/Sanger sequencing** of coding exons, testing for **copy-number changes/deletions** when indicated, and consideration of **multiple tissues** if mosaicism is suspected. | (pqac-00000024, pqac-00000025, pqac-00000026, pqac-00000027, pqac-00000030) |
| HRM screening | **High-resolution melting (HRM)** has been reported as a rapid, low-cost screening assay for **PORCN** exons in clinically suspected FDH, with **Sanger sequencing** used for confirmation and **ARMS** used for validation in the reported workflow. Limitation: HRM may miss some larger deletions. | (pqac-00000024, pqac-00000025, pqac-00000026) |
| Management: multidisciplinary care | Management is **multidisciplinary and supportive**, involving dermatology, genetics, dentistry, orthopedics/plastic surgery, ophthalmology, and other specialties as needed. Goals include improving function/appearance, surveillance for complications, and **genetic counseling**. | (pqac-00000003, pqac-00000032, pqac-00000037) |
| Management: surgery / dental / endocrine examples | Reported interventions include **orthopedic/plastic surgery** for limb malformations (e.g., syndactyly correction), **preventive dental care** (dietary advice, fluoride, fissure sealants, plaque control, restorative treatment), and a recent case of **long-acting growth hormone** for documented GH deficiency/short stature with improved growth and no side effects during follow-up. | (pqac-00000032, pqac-00000036, pqac-00000031, pqac-00000034) |


*Table: This table condenses the most decision-relevant facts on focal dermal hypoplasia/Goltz syndrome: terminology, PORCN genetics, hallmark phenotypes, reported epidemiologic figures, and current diagnostic and management approaches. It is useful as a quick-reference artifact for disease knowledge base curation.*