Variability of Phenotypic and Prenatal Ultrasound Findings of Muenke Syndrome: a Case Report
Prenatal Genetics
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Primary Categories:
- Prenatal Genetics
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Secondary Categories:
- Prenatal Genetics
Introduction
Muenke syndrome is a craniosynostosis syndrome associated with the p.Pro250Arg pathogenic variant in fibroblast growth factor receptor gene (FGFR3) and is inherited in an autosomal dominant manner. It is characterized by considerable phenotypic variability; features may include synostosis of sutures, macrocephaly, temporal bossing, widely spaced eyes, hearing loss, developmental delay, intracranial anomalies, ocular anomalies, brachydactyly, and other radiographic findings including short and broad middle phalanges. Of note, some individuals who have the p.Pro250Arg pathogenic variant may have no signs of Muenke syndrome on physical or radiographic examination. The purpose of this case report is to increase awareness of the phenotypic variability as well as the variability of ultrasound findings in regards to the gestational age at presentation seen in Muenke syndrome.
Case Presentation
A 33 year old (gravida 2, Para 0) was referred to Maternal-Fetal Medicine for an anatomical survey and genetic counseling for baby A. Of note, the patient and her mother had a history of craniosynostosis, and shortened 5th fingers with curved hands. She had a history of bicoronal repair as a child, and had no other neurocognitive deficits.
Diagnostic Workup
The patient had non-invasive prenatal screening which resulted in a low-risk female fetus, and her anatomy ultrasound at 20 weeks and 6 days demonstrated no abnormalities, along with fetal skull sutures that appeared open at the time. After genetic counseling, the patient pursued craniosynostosis panel diagnostic testing which demonstrated a pathogenic variant of c.749>G (p.Pro250Arg) in FGFR3. A follow-up ultrasound was completed at 36 weeks and 5 days that demonstrated frontal bossing and mild polyhydramnios, concerning for fetal craniosynostosis.
The patient had another pregnancy the following year and an early referral to Maternal-Fetal Medicine for anatomical survey and genetic counseling for baby B given the findings in her previous pregnancy. She initially had noninvasive prenatal testing that demonstrated a low-risk male fetus. On the detailed anatomy ultrasound at 20 weeks and 5 days however, baby B appeared to have frontal bossing and a scalloped shaped skull which was concerning for an early diagnosis of fetal craniosynostosis compared to her last pregnancy. Follow-up ultrasounds continued to demonstrate persistent features concerning for fetal craniosynostosis, as well as large for gestational age and polyhydramnios.
Treatment and Management
At 39 weeks and 0 days in her initial pregnancy with baby A, the patient underwent induction of labor resulting in an uncomplicated vaginal delivery, and cord blood was collected for genetic testing. Baby A was found to have the same pathological variant for Muenke syndrome as the patient. Furthermore with baby B, at 39 weeks and 1 day she presented in labor and underwent a primary cesarean section due non-reassuring fetal heart tracing. Cord blood confirmed that neonate was also affected by the pathologic variant of Muenke syndrome.
Outcome and Follow-Up
Baby A underwent bicoronal repair with pediatric neurosurgery at 9 months of age, and has been meeting developmental milestones. In addition, Baby B also underwent bicoronal repair with pediatric neurosurgery at 9 months of age, and has also been meeting developmental milestones.
Discussion
We report cases of Muenke syndrome affecting multiple members of the same family. Our cases further define the phentotypic variations within one family, as well as variability of timing of presentation of symptoms on prenatal ultrasound.
Conclusion
This case highlights the importance of early referral to Maternal-Fetal Medicine and genetic counseling for antenatal surveillance. Surveillance may include serial ultrasounds throughout the prenatal period. Genetic counseling and testing should be offered to families with a history of Muenke syndrome for early detection and neonatal management. Additionally, this case also includes the importance of neonatal follow up and multidisciplinary care which is important for optimal outcomes in these neonates.
Muenke syndrome is a craniosynostosis syndrome associated with the p.Pro250Arg pathogenic variant in fibroblast growth factor receptor gene (FGFR3) and is inherited in an autosomal dominant manner. It is characterized by considerable phenotypic variability; features may include synostosis of sutures, macrocephaly, temporal bossing, widely spaced eyes, hearing loss, developmental delay, intracranial anomalies, ocular anomalies, brachydactyly, and other radiographic findings including short and broad middle phalanges. Of note, some individuals who have the p.Pro250Arg pathogenic variant may have no signs of Muenke syndrome on physical or radiographic examination. The purpose of this case report is to increase awareness of the phenotypic variability as well as the variability of ultrasound findings in regards to the gestational age at presentation seen in Muenke syndrome.
Case Presentation
A 33 year old (gravida 2, Para 0) was referred to Maternal-Fetal Medicine for an anatomical survey and genetic counseling for baby A. Of note, the patient and her mother had a history of craniosynostosis, and shortened 5th fingers with curved hands. She had a history of bicoronal repair as a child, and had no other neurocognitive deficits.
Diagnostic Workup
The patient had non-invasive prenatal screening which resulted in a low-risk female fetus, and her anatomy ultrasound at 20 weeks and 6 days demonstrated no abnormalities, along with fetal skull sutures that appeared open at the time. After genetic counseling, the patient pursued craniosynostosis panel diagnostic testing which demonstrated a pathogenic variant of c.749>G (p.Pro250Arg) in FGFR3. A follow-up ultrasound was completed at 36 weeks and 5 days that demonstrated frontal bossing and mild polyhydramnios, concerning for fetal craniosynostosis.
The patient had another pregnancy the following year and an early referral to Maternal-Fetal Medicine for anatomical survey and genetic counseling for baby B given the findings in her previous pregnancy. She initially had noninvasive prenatal testing that demonstrated a low-risk male fetus. On the detailed anatomy ultrasound at 20 weeks and 5 days however, baby B appeared to have frontal bossing and a scalloped shaped skull which was concerning for an early diagnosis of fetal craniosynostosis compared to her last pregnancy. Follow-up ultrasounds continued to demonstrate persistent features concerning for fetal craniosynostosis, as well as large for gestational age and polyhydramnios.
Treatment and Management
At 39 weeks and 0 days in her initial pregnancy with baby A, the patient underwent induction of labor resulting in an uncomplicated vaginal delivery, and cord blood was collected for genetic testing. Baby A was found to have the same pathological variant for Muenke syndrome as the patient. Furthermore with baby B, at 39 weeks and 1 day she presented in labor and underwent a primary cesarean section due non-reassuring fetal heart tracing. Cord blood confirmed that neonate was also affected by the pathologic variant of Muenke syndrome.
Outcome and Follow-Up
Baby A underwent bicoronal repair with pediatric neurosurgery at 9 months of age, and has been meeting developmental milestones. In addition, Baby B also underwent bicoronal repair with pediatric neurosurgery at 9 months of age, and has also been meeting developmental milestones.
Discussion
We report cases of Muenke syndrome affecting multiple members of the same family. Our cases further define the phentotypic variations within one family, as well as variability of timing of presentation of symptoms on prenatal ultrasound.
Conclusion
This case highlights the importance of early referral to Maternal-Fetal Medicine and genetic counseling for antenatal surveillance. Surveillance may include serial ultrasounds throughout the prenatal period. Genetic counseling and testing should be offered to families with a history of Muenke syndrome for early detection and neonatal management. Additionally, this case also includes the importance of neonatal follow up and multidisciplinary care which is important for optimal outcomes in these neonates.
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