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PubMed This is a summary of 10 peer-reviewed journal articles Updated
Maternal-Fetal Medicine

Prenatal Diagnosis: Deciphering Ultrasounds and Genetic Reports

At a Glance

A prenatal diagnosis of Fryns syndrome is typically confirmed by identifying specific ultrasound signs, like a congenital diaphragmatic hernia and underdeveloped lungs, alongside genetic testing that shows variants in the PIGN gene inherited from both parents.

Navigating prenatal care when there is a suspected diagnosis of Fryns syndrome often feels like learning a new, difficult language. Understanding the terms on your ultrasound and genetic reports can help you feel more prepared for conversations with your medical team.

Decoding the Ultrasound

When a sonographer or maternal-fetal medicine specialist looks for signs of Fryns syndrome, they are searching for a specific “pattern” of development.

  • Congenital Diaphragmatic Hernia (CDH): This is often the first sign detected. It is a hole in the diaphragm (the muscle that separates the chest from the belly) [1][2].
  • Mediastinal Shift: Because abdominal organs (like the stomach) move through the hole into the chest, they push against the heart. A “mediastinal shift” means the heart has been pushed out of its normal central position to one side [2].
  • Pulmonary Hypoplasia: This is the most critical factor for survival. It means the lungs are “underdeveloped” or too small [2][3]. Because the stomach and other organs are taking up space in the chest, the lungs don’t have room to grow to a size that can support breathing after birth.
  • Distal Digital Hypoplasia: Doctors look closely at the baby’s hands and feet. This term means the very tips of the fingers or toes (the “distal” parts) appear unusually small or underdeveloped [3][4].
  • Polyhydramnios: This is an excess of amniotic fluid around the baby. It often happens in Fryns syndrome because the baby may have trouble swallowing the fluid normally due to the structural changes in the chest and abdomen [5].
    • What this means for the mother: Excess fluid can cause severe discomfort and breathlessness for the pregnant mother. It also significantly increases the risk of preterm labor [5]. Your obstetrician will need to monitor you closely for maternal safety.

Understanding the Genetic Report

While ultrasound shows the effects, genetic testing looks for the cause.

  • Whole Exome Sequencing (WES): This is a highly detailed genetic test that “spells out” the most important parts of the baby’s DNA [6]. If your report says Trio-WES, it means they tested the baby’s DNA directly against both parents’ DNA [7]. This definitively proves that the baby inherited one changed gene from each parent, which confirms the diagnosis.
  • The PIGN Gene: For a definitive genetic diagnosis of Fryns syndrome, the report must usually show biallelic variants in the PIGN gene [5][3]. “Biallelic” means there is a change in both copies of the gene.

Sorting Through “Look-Alike” Conditions

Because Fryns syndrome is rare, it can sometimes be confused with other conditions that have similar features.

Condition Primary Gene / Cause Key Difference from Fryns Syndrome
Fryns Syndrome PIGN Defined by the triad of CDH, facial differences, and limb anomalies [3].
Pallister-Killian Syndrome (PKS) Tetrasomy 12p A chromosomal condition that commonly causes CDH and facial differences, but often includes distinct skin pigmentation changes and differences in the baby’s scalp hair.
Lujan-Fryns Syndrome MED12 Despite the similar name, this is entirely different. It is X-linked (mostly affecting males) and does not typically involve CDH [8].
MCAHS1 PIGN Caused by the same gene but usually involves “missense” variants that allow for more lung development and survival, though with severe neurological challenges [5].
Cornelia de Lange NIPBL Can involve CDH, but often includes different limb patterns and heavy facial hair (hirsutism) [9].

To confirm Fryns syndrome, your medical report should ideally show the “cardinal” physical features on imaging AND/OR the presence of biallelic PIGN gene variants [5][10].

Return to the Home Page

Common questions in this guide

What does a congenital diaphragmatic hernia (CDH) mean on my baby's ultrasound?
A congenital diaphragmatic hernia is a hole in the muscle separating the chest from the belly. This allows abdominal organs like the stomach to move into the chest, which can press against the heart and limit lung growth.
Why is pulmonary hypoplasia critical in Fryns syndrome?
Pulmonary hypoplasia means the baby's lungs are underdeveloped or too small. Because abdominal organs take up space in the chest due to the hernia, the lungs do not have enough room to grow to a size that can support breathing after birth.
What does the PIGN gene have to do with Fryns syndrome?
Variants in the PIGN gene are the primary genetic cause of Fryns syndrome. A definitive genetic diagnosis usually requires a test showing that the baby inherited changed copies of the PIGN gene from both parents.
Why does Fryns syndrome cause extra amniotic fluid (polyhydramnios)?
Polyhydramnios is an excess of amniotic fluid around the baby. It occurs because structural changes in the baby's chest and abdomen make it difficult for them to swallow the fluid normally during pregnancy.
How is Fryns syndrome different from Pallister-Killian syndrome?
While both can cause a diaphragmatic hernia and facial differences, Pallister-Killian is caused by a different genetic change called Tetrasomy 12p. It also frequently involves distinct skin pigmentation and scalp hair differences not typically seen in Fryns syndrome.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is the Lung-to-Head Ratio (LHR), and what does it tell us about the severity of the pulmonary hypoplasia?
  2. 2.Does the genetic report specifically identify 'pathogenic' or 'likely pathogenic' variants in the PIGN gene?
  3. 3.Were both parents tested (Trio-WES) to confirm we are both carriers of the same PIGN variant?
  4. 4.How is the excess amniotic fluid (polyhydramnios) being monitored, and what does it mean for my own safety during the rest of the pregnancy?
  5. 5.If the genetic testing is 'negative' for PIGN, how are we confirming it is Fryns syndrome versus a similar-looking condition like Pallister-Killian?

Questions For You

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References

References (10)
  1. 1

    When Fryn met Edward: Two rare syndromes in a single patient.

    Nandan N, Raman VS, Dey S, Dwivedi D

    Medical journal, Armed Forces India 2022; (78(1)):109-112 doi:10.1016/j.mjafi.2019.10.005.

    PMID: 35035054
  2. 2

    Craniorachischisis Totalis with Congenital Diaphragmatic Hernia-A Rare Presentation of Fryns Syndrome.

    Singh A, Pilli GS, Bannur H

    Fetal and pediatric pathology 2016; (35(3)):192-8 doi:10.3109/15513815.2016.1155681.

    PMID: 27064748
  3. 3

    Recessive loss of function PIGN alleles, including an intragenic deletion with founder effect in La Réunion Island, in patients with Fryns syndrome.

    Alessandri JL, Gordon CT, Jacquemont ML, et al.

    European journal of human genetics : EJHG 2018; (26(3)):340-349 doi:10.1038/s41431-017-0087-x.

    PMID: 29330547
  4. 4

    Prenatal Ultrasound Diagnosis of Congenital Diaphragmatic Hernia in a Fetus With Fryns "Anophthalmia-Plus" Syndrome: A Case Report.

    Maritsa VA, Psarris A, Koutras A, et al.

    Cureus 2024; (16(8)):e68000 doi:10.7759/cureus.68000.

    PMID: 39347350
  5. 5

    Biallelic variants in PIGN cause Fryns syndrome, multiple congenital anomalies-hypotonia-seizures syndrome, and neurologic phenotypes: A genotype-phenotype correlation study.

    Loong L, Tardivo A, Knaus A, et al.

    Genetics in medicine : official journal of the American College of Medical Genetics 2023; (25(1)):37-48 doi:10.1016/j.gim.2022.09.007.

    PMID: 36322149
  6. 6

    Application of Whole-Exome Sequencing in the Prenatal Diagnosis of Foetuses With Central Nervous System Abnormalities.

    Luo C, Wen E, Liu Y, et al.

    Molecular genetics & genomic medicine 2024; (12(10)):e70016 doi:10.1002/mgg3.70016.

    PMID: 39359128
  7. 7

    Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities.

    Drury S, Williams H, Trump N, et al.

    Prenatal diagnosis 2015; (35(10)):1010-7 doi:10.1002/pd.4675.

    PMID: 26275891
  8. 8

    Tentative clinical diagnosis of Lujan-Fryns syndrome--A conglomeration of different genetic entities?

    Hackmann K, Rump A, Haas SA, et al.

    American journal of medical genetics. Part A 2016; (170A(1)):94-102 doi:10.1002/ajmg.a.37378.

    PMID: 26358559
  9. 9

    Cornelia de Lange syndrome: To diagnose or not to diagnose in utero?

    Avagliano L, Bulfamante GP, Massa V

    Birth defects research 2017; (109(10)):771-777 doi:10.1002/bdr2.1045.

    PMID: 28544538
  10. 10

    Diaphragmatic Hernia as a Prenatal Feature of Glycosylphosphatidylinositol Biosynthesis Defects and the Overlap With Fryns Syndrome - Literature Review.

    Kosinski P, Greczan M, Jezela-Stanek A

    Frontiers in genetics 2021; (12()):674722 doi:10.3389/fgene.2021.674722.

    PMID: 34163527

This page provides educational information on interpreting prenatal ultrasound and genetic testing for Fryns syndrome. Always consult your maternal-fetal medicine specialist or genetic counselor to discuss your specific medical reports.

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