Fetal for Tuesday, June 2nd, 2026

Contributed by Nemours Children's Hospital
Sukriti Chaudhri, Kriti Gwal, Lauren May, and Jennifer Kucera .

History

A 23-year-old healthy primigravida female presented at 19 weeks gestation for a fetal anatomy scan. A review of her prenatal records was unremarkable with no family history of congenital malformations, birth defects, or chromosomal abnormalities. Abnormal findings on fetal anatomy ultrasound warranted fetal MRI, which was performed at 24 weeks gestation, revealing a number of abnormalities.

Images (Click any image to enlarge)

Top row: Transverse, Sagittal, and Oblique Coronal US images showing [A] bilateral hyperechoic lungs (green asterisks) with centralization of heart (red arrowhead), [B] echogenic lung with a flattened hemidiaphragm (purple arrow), and [C] a fluid filled dilated trachea (green arrowhead) Bottom row: Coronal [D] and sagittal [E] T2- weighted SSFSE (single shot fast spin echo) images show a fluid filled dilated trachea (white arrow) and mainstem bronchi with upstream obstruction at the level of the larynx (yellow arrow), enlarged T2 hyperintense lungs, and flattened diaphragms (purple arrow).
Coronal [F] and axial [G] T2-weighted single shot fast spin echo (SSFSE) images show normal left renal parenchyma (orange arrowhead) and a multicystic dysplastic right kidney (pink arrowhead) with suggested fusion of the lower pole of the kidneys at the midline. Ascites is also present (green asterisks). Axial diffusion weighted image [H] confirms the horseshoe configuration of kidneys.
Axial T2-weighted SSFSE images show skin covering the globes (green arrows) in [I]. Subcutaneous edema is also identified at the scalp soft tissues in [J] (red arrowheads).
4 chamber view in fetal echo without [K] and with doppler [L] revealed a ventricular septal defect (green arrowhead). There was also presence of only one bone (radius or ulna) in the right forearm (pink asterisks) [M] while both the radius and ulna were seen in the left forearm [N].

Question

The fetus is most likely affected by which of these conditions?

Your answer

Please log in to see your results.

Correct answer

Fraser syndrome

Discussion

Congenital high airway obstruction syndrome (CHAOS) represents an uncommon fetal condition characterized by partial or complete obstruction of the upper airway, involving the larynx or trachea. The obstruction may arise from intrinsic causes such as laryngeal or tracheal atresia or webs, or from extrinsic compression. Impaired egress of fluid normally produced by the fetal lungs results in progressive accumulation within the bronchial tree and alveoli, leading to marked pulmonary enlargement. Characteristic enlarged and hyperexpanded lungs are associated with flattening or inversion of the diaphragmatic contours (1).

Prenatal imaging plays a pivotal role in diagnosis. Both sonography and fetal MRI demonstrate hallmark features that help distinguish CHAOS from other fetal thoracic pathologies. Bilateral lung enlargement with hyperechogenicity on ultrasound (or T2 hyperintensity on MRI), dilatation of the tracheobronchial tree distal to the level of obstruction, and diaphragmatic inversion may occur. Secondary effects from mass effect of the distended lungs include central displacement of the heart and great vessels. Progressive impairment of venous return due to increased intrathoracic pressure predisposes the affected fetus to hydrops fetalis (excess fluid in two compartments), which significantly worsens prognosis (1).

CHAOS is frequently associated with syndromic conditions, most notably Fraser syndrome, a rare autosomal recessive disorder with multisystem involvement. Fraser syndrome is characterized by a constellation of anomalies including cryptophthalmos (failure of normal eyelid development with continuous skin covering the globes), syndactyly, urogenital malformations, laryngotracheal abnormalities, craniofacial dysmorphism, and skeletal defects (2). The genetic basis has been linked to mutations in genes involved in epithelial–mesenchymal adhesion and extracellular matrix integrity, including FRAS1, FREM2, and GRIP1 (3).

Diagnosis of Fraser syndrome relies on a combination of clinical and imaging findings based on established criteria. The current diagnostic framework requires either three major criteria, two major and two minor criteria, or one major and three minor criteria. Major features include syndactyly, cryptophthalmos, ambiguous genitalia, urinary tract anomalies, laryngeal or tracheal defects, and a positive family history, whereas minor features encompass anorectal malformations, dysplastic ears, cranial ossification defects, umbilical abnormalities, and nasal anomalies (4).

Prenatal detection of Fraser syndrome is often challenging, as some defining features such as cryptophthalmos and syndactyly may not be readily appreciable on imaging. Therefore, diagnosis frequently relies on identifying more conspicuous findings such as renal anomalies, laryngotracheal obstruction (manifesting as CHAOS), and associated structural abnormalities, especially when supported by family history (5).

Given the multisystem involvement, comprehensive prenatal assessment is essential, followed by detailed postnatal evaluation to confirm additional phenotypic features that are better assessed clinically, including external genital anomalies, syndactyly, and ocular abnormalities. The overall prognosis of Fraser syndrome remains poor and is largely determined by the severity of associated anomalies, particularly airway obstruction and renal involvement. Early prenatal diagnosis allows for appropriate counseling, delivery planning, and--in severe cases--arrangement of palliative care (6).

References

  • 1. Mong, A., Johnson, A.M., Kramer, S.S. et al. Congenital high airway obstruction syndrome: MR/US findings, effect on management, and outcome. Pediatr Radiol 38, 1171–1179 (2008). https://doi.org/10.1007/s00247-008-0962-2 2. van Haelst MM, Scambler PJ, Hennekam RC - Fraser syndrome: A clinical study of 59 cases and evaluation of diagnostic criteria. Am J Med Genet. 2007; 143a: 3194–203. doi: 10.1002/ajmg.a.31951. 3. van Haelst, M.M., Maiburg, M., Baujat, G., Jadeja, S., Monti, E., Bland, E., Pearce, K., Fraser Syndrome Collaboration Group, Hennekam, R.C. and Scambler, P.J. (2008), Molecular study of 33 families with Fraser syndrome new data and mutation review. Am. J. Med. Genet., 146A: 2252-2257. https://doi.org/10.1002/ajmg.a.32440 4. McGregor L, Makela V, Darling SM, et al. - Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet. 2003; 34: 203–208. doi: 10.1038/ng1142. 5. van Haelst, M.M., Scambler, P.J., Fraser Syndrome Collaboration Group and Hennekam, R.C.M. (2007), Fraser syndrome: A clinical study of 59 cases and evaluation of diagnostic criteria. Am. J. Med. Genet., 143A: 3194-3203. https://doi.org/10.1002/ajmg.a.31951 6. Bouaoud J, Olivetto M, Testelin S, Dakpe S, Bettoni J, Devauchelle B. Fraser syndrome: review of the literature illustrated by a historical adult case. Int J Oral Maxillofac Surg. 2020 Oct; 49(10): 1245-1253. doi: 10.1016/j.ijom.2020.01.007. Epub 2020 Jan 22. PMID: 31982235.