Neurofibromatosis type 1 screening: Difference between revisions

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*[Condition 3]
*[Condition 3]


<br />
=== Risk to Family Members ===
'''Parents of a proband'''
* Approximately 50% of individuals diagnosed with NF1 have an affected parent.
* Approximately 50% of individuals diagnosed with NF1 have the disorder as the result of a ''de novo'' ''NF1'' pathogenic variant.
* Recommendations for the evaluation of parents of a proband with an apparent ''de novo'' pathogenic variant (i.e., neither parent is known to have NF1) include medical history and physical examination with particular attention to dermal and other features of NF1. In addition, an ophthalmologic examination (including slit lamp examination and infrared reflectance imaging or optical coherence tomography) should be performed on both parents to look for Lisch nodules, choroidal freckling, or other ophthalmologic signs of NF1.
* If neither parent of an individual with NF1 meets the clinical diagnostic criteria for NF1 after careful medical history, physical examination, and ophthalmologic examination, a ''de novo'' pathogenic variant occurring in the proband is the most likely explanation. Germline mosaicism in a parent with no clinical signs of NF1 is possible but much less likely [Lázaro et al 1995, Bottillo et al 2010, Trevisson et al 2014].
* The family history may appear to be negative because of failure to recognize NF1 in family members or early death of a parent before the recognition of signs or symptoms.
* Note: An individual in whom NF1 appears to have arisen as the result of ''de novo'' mutation may have somatic mosaicism associated with segmental or unusually mild disease manifestations [Messiaen et al 2011, García-Romero et al 2016]. The risk of a parent with mosaicism for an ''NF1'' pathogenic variant transmitting the disease to his or her child may be less than 50%, but if the pathogenic variant is transmitted, it will be present in every cell in the child's body and s/he may be much more severely affected.
'''Sibs of a proband'''
* The risk to the sibs of the proband depends on the clinical status of the proband's parents.
* If a parent is affected, the risk to the sibs is 50%; a sib who inherits an ''NF1'' pathogenic variant will develop features of NF1, but the disease may be considerably more (or less) severe in an affected sib than in the proband.
* If neither parent of an individual with NF1 meets the clinical diagnostic criteria for NF1 after careful medical history, physical examination, and ophthalmologic examination, the risk to the sibs of the affected individual of having NF1 is low but greater than that of the general population because of the possibility of germline mosaicism. Note: Germline mosaicism for an ''NF1'' pathogenic variant has been demonstrated by molecular testing in a few families in which affected sibs were born to unaffected parents [Bottillo et al 2010, Trevisson et al 2014, Ejerskov et al 2016].
'''Offspring of a proband'''
* Each child of an individual with NF1 has a 50% chance of inheriting the ''NF1'' pathogenic variant.
* Penetrance is 100%; thus, a child who inherits an ''NF1'' pathogenic variant will develop features of NF1, but the disease may be considerably more (or less) severe in an affected child than in his or her affected parent.
'''Other family members.''' The risk to other family members depends on the status of the proband's parents: if a proband's parent is affected, other members of his or her family may be at risk.
'''Possibility of multiple ''de novo'' pathogenic variants in a single family.''' Upadhyaya et al [2003] reported the occurrence of three different ''NF1'' pathogenic variants in one family and advised caution in assuming that the same pathogenic variant is present in all members of an affected family. Two different ''NF1'' pathogenic variants have been reported in another family [Klose et al 1999].
'''Considerations in families with an apparent ''de novo'' pathogenic variant.''' When neither parent of a proband with an autosomal dominant condition has the pathogenic variant identified in the proband or clinical evidence of the disorder, the pathogenic variant is likely ''de novo''. However, non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) and undisclosed adoption may also be considered.
'''Family planning'''
* The optimal time for determination of genetic risk and discussion of the availability of prenatal or preimplantation genetic diagnosis is before pregnancy.
* Genetic counseling (including discussion of potential risks to offspring and reproductive options) should be offered to young adults who are affected or at risk.
'''Molecular genetic testing.''' Once the ''NF1'' pathogenic variant has been identified in an affected family member, prenatal testing [van Minkelen et al 2014] for a pregnancy at increased risk and preimplantation genetic diagnosis [Merker et al 2015] are possible.
'''Ultrasound examination.''' Prenatal diagnosis of exceptionally severe NF1 by prenatal ultrasound examination has been reported [McEwing et al 2006], but ultrasound examination is unlikely to be informative in most cases.
Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.
<br />
* '''[[Neurofibromatosis type 1]]''' manifestations vary widely among patients , from individuals with absent [[symptoms]] to rapidly progessive disorders.<ref name="pmid203012882">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Friedman JM |title= |journal= |volume= |issue= |pages= |date= |pmid=20301288 |doi= |url=}}</ref>
* The most common complication of [[neurofibromatosis type 1]] is [[disfigurement]] due to skin lesions<ref name="pmid29478615">{{cite journal |vauthors=Cimino PJ, Gutmann DH |title=Neurofibromatosis type 1 |journal=Handb Clin Neurol |volume=148 |issue= |pages=799–811 |date=2018 |pmid=29478615 |doi=10.1016/B978-0-444-64076-5.00051-X |url=}}</ref>
* [[Prognosis]] will depend on the number of [[commorbidities]], but it is usually moderately good.<ref name="pmid28230061">{{cite journal |vauthors=Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ |title=Neurofibromatosis type 1 |journal=Nat Rev Dis Primers |volume=3 |issue= |pages=17004 |date=February 2017 |pmid=28230061 |doi=10.1038/nrdp.2017.4 |url=}}</ref>
* [[Life expectancy]] is usually reduced by 8-12 years, beign [[Cancer|malignant tumors]] the most common cause of death.<ref name="pmid28230061" />
==Natural History, Complications, and Prognosis==
=== Natural history ===
* Manifestations vary widely among patients with [[neurofibromatosis type 1]], from individuals with absent symptoms to rapidly progessive disorders.<ref name="pmid203012882" />
* Characteristics of [[neurofibromatosis type 1]] appear at different ages,<ref name="pmid203012882" /><ref name="pmid106991172">{{cite journal |vauthors=DeBella K, Szudek J, Friedman JM |title=Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children |journal=Pediatrics |volume=105 |issue=3 Pt 1 |pages=608–14 |date=March 2000 |pmid=10699117 |doi=10.1542/peds.105.3.608 |url=}}</ref><ref name="pmid16018159">{{cite journal |vauthors=Boulanger JM, Larbrisseau A |title=Neurofibromatosis type 1 in a pediatric population: Ste-Justine's experience |journal=Can J Neurol Sci |volume=32 |issue=2 |pages=225–31 |date=May 2005 |pmid=16018159 |doi=10.1017/s0317167100004017 |url=}}</ref><ref name="pmid19117870">{{cite journal |vauthors=Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL |title=Neurofibromatosis type 1 revisited |journal=Pediatrics |volume=123 |issue=1 |pages=124–33 |date=January 2009 |pmid=19117870 |doi=10.1542/peds.2007-3204 |url=}}</ref> among them:
** Bone manifestations appear from birth.<ref name="pmid203012882" />
** [[Neurofibroma|Plexiform neurofibromas]] appear usually around 1 year of age.<ref name="pmid203012882" />
** [[Café au lait spot|Cafe au lait spots]] appear in the first 5 years of life.<ref name="pmid203012882" />
** [[Optic nerve glioma|Optic gliomas]] develope in the first 6 years of life.<ref name="pmid203012882" />
** [[Scoliosis]] develops between age 6 and 10.<ref name="pmid203012882" />
** Malignant peripheral nerve sheath tumors usually usually appear around adolescence or adulthood.<ref name="pmid203012882" />
* People with [[neurofibromatosis type 1]] tend to grow below average in height and above average in [[head circumference]].<ref name="pmid105888372">{{cite journal |vauthors=Clementi M, Milani S, Mammi I, Boni S, Monciotti C, Tenconi R |title=Neurofibromatosis type 1 growth charts |journal=Am. J. Med. Genet. |volume=87 |issue=4 |pages=317–23 |date=December 1999 |pmid=10588837 |doi=10.1002/(sici)1096-8628(19991203)87:4<317::aid-ajmg7>3.0.co;2-x |url=}}</ref><ref name="pmid108176592">{{cite journal |vauthors=Szudek J, Birch P, Friedman JM |title=Growth charts for young children with neurofibromatosis 1 (NF1) |journal=Am. J. Med. Genet. |volume=92 |issue=3 |pages=224–8 |date=May 2000 |pmid=10817659 |doi= |url=}}</ref><ref name="pmid23466600">{{cite journal |vauthors=Karvonen M, Saari A, Hannila ML, Lönnqvist T, Dunkel L, Sankilampi U |title=Elevated head circumference-to-height ratio is an early and frequent feature in children with neurofibromatosis type 1 |journal=Horm Res Paediatr |volume=79 |issue=2 |pages=97–102 |date=2013 |pmid=23466600 |doi=10.1159/000347119 |url=}}</ref><ref name="pmid203012882" />
* [[Precocious puberty]] and [[delayed puberty]] is more common in individuals with neurofibromatosis type 1 than the general population.<ref name="pmid109699312">{{cite journal |vauthors=Virdis R, Sigorini M, Laiolo A, Lorenzetti E, Street ME, Villani AR, Donadio A, Pisani F, Terzi C, Garavelli L |title=Neurofibromatosis type 1 and precocious puberty |journal=J. Pediatr. Endocrinol. Metab. |volume=13 Suppl 1 |issue= |pages=841–4 |date=July 2000 |pmid=10969931 |doi=10.1515/jpem.2000.13.s1.841 |url=}}</ref><ref name="pmid26666878">{{cite journal |vauthors=Kocova M, Kochova E, Sukarova-Angelovska E |title=Optic glioma and precocious puberty in a girl with neurofibromatosis type 1 carrying an R681X mutation of NF1: case report and review of the literature |journal=BMC Endocr Disord |volume=15 |issue= |pages=82 |date=December 2015 |pmid=26666878 |pmc=4678666 |doi=10.1186/s12902-015-0076-4 |url=}}</ref><ref name="pmid12729406">{{cite journal |vauthors=Virdis R, Street ME, Bandello MA, Tripodi C, Donadio A, Villani AR, Cagozzi L, Garavelli L, Bernasconi S |title=Growth and pubertal disorders in neurofibromatosis type 1 |journal=J. Pediatr. Endocrinol. Metab. |volume=16 Suppl 2 |issue= |pages=289–92 |date=March 2003 |pmid=12729406 |doi= |url=}}</ref><ref name="pmid203012882" />
===Complications===
*Common complications of [[neurofibromatosis type 1]] include:
**[[Depression]] and [[social anxiety]]<ref name="pmid29478615" />
**Chronic pain, numbness, and/or paralysis due to the peripheral nerve sheath tumors<ref name="pmid29478615" />
**Blindness due to [[Optic nerve glioma|optic nerve gliomas]]<ref name="pmid29478615" />
**Amputation due to a tibial [[pseudarthrosis]]<ref name="pmid29478615" />
**[[Disfigurement]] due to skin lesions<ref name="pmid29478615" />
**[[Brain tumors]]<ref name="pmid29478615" />
**Wandering problems due to [[scoliosis]] and/or [[kyphosis]]<ref name="pmid29478615" />
**Malignant degeneration of neurofibromas into malignant periphreal nerve sheath tumor (this occurs in 10-12% of the cases)<ref name="pmid29478615" />
===Prognosis===
* Depending on the extent of the disease progression and the time of diagnosis, the [[prognosis]] may vary. However, the prognosis is generally regarded as moderately good.
* [[Quality of life]] is lower in children and adults with neurofibromatosis type 1, due to the several commorbidities and complications, many times having an incapacitating depression.<ref name="pmid23817811">{{cite journal |vauthors=Vranceanu AM, Merker VL, Park E, Plotkin SR |title=Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature |journal=J. Neurooncol. |volume=114 |issue=3 |pages=257–62 |date=September 2013 |pmid=23817811 |doi=10.1007/s11060-013-1195-2 |url=}}</ref><ref name="pmid24664633">{{cite journal |vauthors=Merker VL, Bredella MA, Cai W, Kassarjian A, Harris GJ, Muzikansky A, Nguyen R, Mautner VF, Plotkin SR |title=Relationship between whole-body tumor burden, clinical phenotype, and quality of life in patients with neurofibromatosis |journal=Am. J. Med. Genet. A |volume=164A |issue=6 |pages=1431–7 |date=June 2014 |pmid=24664633 |doi=10.1002/ajmg.a.36466 |url=}}</ref><ref name="pmid25663248">{{cite journal |vauthors=Vranceanu AM, Merker VL, Park ER, Plotkin SR |title=Quality of life among children and adolescents with neurofibromatosis 1: a systematic review of the literature |journal=J. Neurooncol. |volume=122 |issue=2 |pages=219–28 |date=April 2015 |pmid=25663248 |doi=10.1007/s11060-015-1725-1 |url=}}</ref>
* [[Life expectancy]] in patients with neurofibromatosis type 1 is usually reduced 8-21 years from the normal population.<ref name="pmid28230061" />
* The most common cause of death in these type of patients is due to [[Malignant neoplasms|malignant neoplasm]].<ref name="pmid28230061" />
<br />
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


{{WH}}
{{WS}}
[[Category: (name of the system)]]
[[Category: (name of the system)]]

Revision as of 23:53, 23 June 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with:

  • [Condition 1]
  • [Condition 2]
  • [Condition 3]


Risk to Family Members

Parents of a proband

  • Approximately 50% of individuals diagnosed with NF1 have an affected parent.
  • Approximately 50% of individuals diagnosed with NF1 have the disorder as the result of a de novo NF1 pathogenic variant.
  • Recommendations for the evaluation of parents of a proband with an apparent de novo pathogenic variant (i.e., neither parent is known to have NF1) include medical history and physical examination with particular attention to dermal and other features of NF1. In addition, an ophthalmologic examination (including slit lamp examination and infrared reflectance imaging or optical coherence tomography) should be performed on both parents to look for Lisch nodules, choroidal freckling, or other ophthalmologic signs of NF1.
  • If neither parent of an individual with NF1 meets the clinical diagnostic criteria for NF1 after careful medical history, physical examination, and ophthalmologic examination, a de novo pathogenic variant occurring in the proband is the most likely explanation. Germline mosaicism in a parent with no clinical signs of NF1 is possible but much less likely [Lázaro et al 1995, Bottillo et al 2010, Trevisson et al 2014].
  • The family history may appear to be negative because of failure to recognize NF1 in family members or early death of a parent before the recognition of signs or symptoms.
  • Note: An individual in whom NF1 appears to have arisen as the result of de novo mutation may have somatic mosaicism associated with segmental or unusually mild disease manifestations [Messiaen et al 2011, García-Romero et al 2016]. The risk of a parent with mosaicism for an NF1 pathogenic variant transmitting the disease to his or her child may be less than 50%, but if the pathogenic variant is transmitted, it will be present in every cell in the child's body and s/he may be much more severely affected.

Sibs of a proband

  • The risk to the sibs of the proband depends on the clinical status of the proband's parents.
  • If a parent is affected, the risk to the sibs is 50%; a sib who inherits an NF1 pathogenic variant will develop features of NF1, but the disease may be considerably more (or less) severe in an affected sib than in the proband.
  • If neither parent of an individual with NF1 meets the clinical diagnostic criteria for NF1 after careful medical history, physical examination, and ophthalmologic examination, the risk to the sibs of the affected individual of having NF1 is low but greater than that of the general population because of the possibility of germline mosaicism. Note: Germline mosaicism for an NF1 pathogenic variant has been demonstrated by molecular testing in a few families in which affected sibs were born to unaffected parents [Bottillo et al 2010, Trevisson et al 2014, Ejerskov et al 2016].

Offspring of a proband

  • Each child of an individual with NF1 has a 50% chance of inheriting the NF1 pathogenic variant.
  • Penetrance is 100%; thus, a child who inherits an NF1 pathogenic variant will develop features of NF1, but the disease may be considerably more (or less) severe in an affected child than in his or her affected parent.

Other family members. The risk to other family members depends on the status of the proband's parents: if a proband's parent is affected, other members of his or her family may be at risk.

Possibility of multiple de novo pathogenic variants in a single family. Upadhyaya et al [2003] reported the occurrence of three different NF1 pathogenic variants in one family and advised caution in assuming that the same pathogenic variant is present in all members of an affected family. Two different NF1 pathogenic variants have been reported in another family [Klose et al 1999].

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with an autosomal dominant condition has the pathogenic variant identified in the proband or clinical evidence of the disorder, the pathogenic variant is likely de novo. However, non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) and undisclosed adoption may also be considered.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal or preimplantation genetic diagnosis is before pregnancy.
  • Genetic counseling (including discussion of potential risks to offspring and reproductive options) should be offered to young adults who are affected or at risk.


Molecular genetic testing. Once the NF1 pathogenic variant has been identified in an affected family member, prenatal testing [van Minkelen et al 2014] for a pregnancy at increased risk and preimplantation genetic diagnosis [Merker et al 2015] are possible.

Ultrasound examination. Prenatal diagnosis of exceptionally severe NF1 by prenatal ultrasound examination has been reported [McEwing et al 2006], but ultrasound examination is unlikely to be informative in most cases.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Natural History, Complications, and Prognosis

Natural history

Complications

Prognosis

  • Depending on the extent of the disease progression and the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as moderately good.
  • Quality of life is lower in children and adults with neurofibromatosis type 1, due to the several commorbidities and complications, many times having an incapacitating depression.[13][14][15]
  • Life expectancy in patients with neurofibromatosis type 1 is usually reduced 8-21 years from the normal population.[3]
  • The most common cause of death in these type of patients is due to malignant neoplasm.[3]


References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Friedman JM. PMID 20301288. Vancouver style error: initials (help); Missing or empty |title= (help)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Cimino PJ, Gutmann DH (2018). "Neurofibromatosis type 1". Handb Clin Neurol. 148: 799–811. doi:10.1016/B978-0-444-64076-5.00051-X. PMID 29478615.
  3. ↑ 3.0 3.1 3.2 3.3 Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ (February 2017). "Neurofibromatosis type 1". Nat Rev Dis Primers. 3: 17004. doi:10.1038/nrdp.2017.4. PMID 28230061.
  4. ↑ DeBella K, Szudek J, Friedman JM (March 2000). "Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children". Pediatrics. 105 (3 Pt 1): 608–14. doi:10.1542/peds.105.3.608. PMID 10699117.
  5. ↑ Boulanger JM, Larbrisseau A (May 2005). "Neurofibromatosis type 1 in a pediatric population: Ste-Justine's experience". Can J Neurol Sci. 32 (2): 225–31. doi:10.1017/s0317167100004017. PMID 16018159.
  6. ↑ Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL (January 2009). "Neurofibromatosis type 1 revisited". Pediatrics. 123 (1): 124–33. doi:10.1542/peds.2007-3204. PMID 19117870.
  7. ↑ Clementi M, Milani S, Mammi I, Boni S, Monciotti C, Tenconi R (December 1999). "Neurofibromatosis type 1 growth charts". Am. J. Med. Genet. 87 (4): 317–23. doi:10.1002/(sici)1096-8628(19991203)87:4<317::aid-ajmg7>3.0.co;2-x. PMID 10588837.
  8. ↑ Szudek J, Birch P, Friedman JM (May 2000). "Growth charts for young children with neurofibromatosis 1 (NF1)". Am. J. Med. Genet. 92 (3): 224–8. PMID 10817659.
  9. ↑ Karvonen M, Saari A, Hannila ML, Lönnqvist T, Dunkel L, Sankilampi U (2013). "Elevated head circumference-to-height ratio is an early and frequent feature in children with neurofibromatosis type 1". Horm Res Paediatr. 79 (2): 97–102. doi:10.1159/000347119. PMID 23466600.
  10. ↑ Virdis R, Sigorini M, Laiolo A, Lorenzetti E, Street ME, Villani AR, Donadio A, Pisani F, Terzi C, Garavelli L (July 2000). "Neurofibromatosis type 1 and precocious puberty". J. Pediatr. Endocrinol. Metab. 13 Suppl 1: 841–4. doi:10.1515/jpem.2000.13.s1.841. PMID 10969931.
  11. ↑ Kocova M, Kochova E, Sukarova-Angelovska E (December 2015). "Optic glioma and precocious puberty in a girl with neurofibromatosis type 1 carrying an R681X mutation of NF1: case report and review of the literature". BMC Endocr Disord. 15: 82. doi:10.1186/s12902-015-0076-4. PMC 4678666. PMID 26666878.
  12. ↑ Virdis R, Street ME, Bandello MA, Tripodi C, Donadio A, Villani AR, Cagozzi L, Garavelli L, Bernasconi S (March 2003). "Growth and pubertal disorders in neurofibromatosis type 1". J. Pediatr. Endocrinol. Metab. 16 Suppl 2: 289–92. PMID 12729406.
  13. ↑ Vranceanu AM, Merker VL, Park E, Plotkin SR (September 2013). "Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature". J. Neurooncol. 114 (3): 257–62. doi:10.1007/s11060-013-1195-2. PMID 23817811.
  14. ↑ Merker VL, Bredella MA, Cai W, Kassarjian A, Harris GJ, Muzikansky A, Nguyen R, Mautner VF, Plotkin SR (June 2014). "Relationship between whole-body tumor burden, clinical phenotype, and quality of life in patients with neurofibromatosis". Am. J. Med. Genet. A. 164A (6): 1431–7. doi:10.1002/ajmg.a.36466. PMID 24664633.
  15. ↑ Vranceanu AM, Merker VL, Park ER, Plotkin SR (April 2015). "Quality of life among children and adolescents with neurofibromatosis 1: a systematic review of the literature". J. Neurooncol. 122 (2): 219–28. doi:10.1007/s11060-015-1725-1. PMID 25663248.
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