Case Report

Neurofibromatosis-1 and Pregnancy: Case report

Kalmantis K1, Petsa A1, Daskalakis G2, Alexopoulos E1, Korovesi E3, Antsaklis P2, Karagkiouzis T3

1Department of Obstetrics & Gynecology, “Alexandra” Hospital, Athens, Greece
2First Department of Obstetrics & Gynecology, Alexandra Hospital, Athens, Greece
3Maternity Hospital Iaso, Athens, Greece

Correspondence: Kalmantis Konstantinos, 15, Ifigenias str, P. Faliro, Athens Greece, E-mail: Tel: 0030 6972839327


Introduction: Neurofibromatosis type-1 (NF-1) is one of the most common genetic diseases following an autosomal dominant inheritance pattern. Maternal and fetal complications have been reported. Purpose: To present a very interesting and rare case report regarding neurofibromatosis – 1 (NF-1) in pregnancy and to create a complete review concerning this genetic disease. Materials and Methods: Articles were identified through electronic databases; no date or language restrictions were placed; relevant citations were hand searched. The search was conducted using the following terms: neurofibromatosis, neurofibromatosis type-1, pregnancy. Case presentation: We present a case of a 36-year-old nulliparous pregnant woman affected by NF-1. She presented with café-au-lait spots and cutaneous/subcutaneous neurofibromas, progressively increasing in size and number. The unique obstetric complication was placenta previa, diagnosed in the second trimester. A caesarean section was performed on the 36th week. A healthy male neonate unaffected by NF-1 was born. Both post-operative period and puerperium were uneventful. Conclusions: This case report highlights the fact that a normal pregnancy outcome can occur in pregnant women with NF-1 and proper counselling should be in place so that informed decisions can be made by future parents.

Keywords: neurofibromatosis, neurofibromatosis type-1, pregnancy


Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder with variable clinical manifestations, such as café-an-lait spots, axillary freckling, cutaneous neurofibromas and iris hamartomas (Lisch nodules), occuring in most patients. It is characterized by different types of mutations of the NF-1 gene1, 2. Approximately 50% of the NF-1 gene mutations result from de novo mutations3-5. The reported incidence of neurofibromatosis (NF) in pregnancy varies from 1:5000 to 1:18.5006.

The management in cases of NF-1 complicating pregnancy is crucial since there is limited information available on pregnant women with NF-1. Current obstetrical bibliography reports that this group of women has an increased risk of complications. NF-1 is associated with fetal complications, such as spontaneous miscarriage, preterm delivery, intrauterine growth retardation, and stillbirths, as well as maternal disease aggravation (hypertensive and cerebrovascular complications)7,8 We present a case of NF-1 complicating pregnancy and a short review of the literature. (Table 1)

Case presentation

A 36-year-old nulliparous pregnant woman affected by NF1 presented in the outpatient department of “Alexandra” Maternity Hospital, Athens. She had no previous family history of this disorder. On clinical examination, she had café-au-lait spots and multiple lesions of NF of variable sizes (cutaneous and subcutaneous), which – according to the patient – had been increasing in size and number (Figure 1). The latest magnetic resonance imaging exam (MRI) of the brain and spine was performed two months prior to current pregnancy and revealed demyelination lesions of the brain and arteriovenous malformation (AVM) of subarachnoid space of the cervical spine. On admission, the cardiovascular assessment did not reveal hypertension or any other cardiovascular disease and neither did the neurosurgical assessment. The patient underwent typical prenatal screening examinations. Genetic counselling was also offered to the couple regarding prenatal invasive procedures (chorionic villus sampling or amniocentesis). During pregnancy, no obstetric complications occurred apart from the diagnosis of placenta previa during the 18-23 weeks’ ultrasound scan. The pregnancy was uncomplicated until the 36th week of gestation when a caesarean section was performed due to spontaneous onset of labor and the presence of placenta previa. It was performed under general anesthesia because of the presence of spinal AVM. A healthy male neonate was born weighing 2650gr.  The neonate was admitted in the Neonate Intensive Care Unit for 3 days. Both the post-operative period and the puerperium were uncomplicated. The neonate was not affected by NF I.

Figure 1. Café-au-lait spots and multiple lesions of neurofibromatosis of variable size.


Neurofibromatosis type 1 is one of the most common genetic disorders, caused by mutations of the NF-1 gene on chromosome 17. This condition can either be inherited, or occur de novo as a result of spontaneous mutations7 The clinical manifestations of NF-1 range from mild cutaneous lesions and axillary freckling to plexiform neurofibromas, optic gliomas, bony abnormalities, pseudoarthosis and malignancies9, 15. About two thirds of the affected population with NF-1 have parents with NF-1 and inherit the disease from one of them. The risk for each child is estimated to be about 50%. The remaining third of the population develops this condition due to spontaneous mutations. It seems that most of the NF-1 mutations reported so far are unique10.

Many authors have suggested that pregnancy complications are more common in women with NF-1. So far, only limited information is available on pregnancy in women with NF-1. Published case reports demonstrate the association with intrauterine growth restriction, eclampsia, oligohydramnios, stillbirth, pregnancy-induced hypertension and preterm labor6-8, 10. Furthermore, pregnancy tends to increase the number and size of cutaneous neurofibromas in women through pregnancy, with an apparent decrease in size subsequent to delivery16. Some neurofibromas contain oestrogen receptors, suggesting the existence of a correlation between the increase in number and size of neurofibromas and the increase in serum oestrogen levels during pregnancy17. An increased rate of cesarean section is also reported. This could be attributed to fetal distress, malpresentations and cephalopelvic disproportion due to undiagnosed pelvic neurofibromas and pelvic contractures, including cases of kyphoscoliosis affecting the lower spine (sequelae of NF-1)16. Many authors suggest to proceed to early termination of pregnancy and sterilization of women because of the adverse effect of pregnancy on the course of the disease, poor pregnancy outcome and the possibility of transmission to the fetus. This decision can only be made by pregnant women 10, 18.

The case report that we present is the fourth study in literature suggesting that NF-1 may not be associated with significant obstetric complications and may have normal pregnancy outcome6. 16, 19. The present case shows that a normal obstetric outcome could be expected in pregnant women with NF-1.

Clinicians have to make an accurate prenatal diagnosis, if possible. The extreme variability of the phenotypic expression of the NF-1 gene makes it very difficult for NF-1 families to decide whether to have children or not, as molecular diagnosis cannot predict clinical expression of the disease20. The psychological management of parents should therefore be very sensitive. Clinicians must discuss with parents the diagnostic possibilities and dilemmas during counseling and should keep in mind that a normal obstetric outcome could also occur in pregnant women with NF-1.


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Received 9-2-2018
Revised 2-3-2018
Accepted 12-3-2018