NF1 is classically autosomal dominant (often de novo), and boards expect you to distinguish this from X-linked and autosomal-recessive patterns.
A 4-year-old girl has 7 cafe-au-lait macules over 5 mm in diameter scattered over her body and Lisch nodules on ophthalmic examination. You diagnose her with type 1 neurofibromatosis.
What is the inheritance pattern of this disorder?
Answer Options:
A. autosomal recessive
B. X-linked dominant
C. X-linked recessive
D. autosomal dominant
NF1 results from pathogenic variants in the NF1 tumor suppressor gene and is inherited in an autosomal-dominant pattern with variable expressivity. A major exam nuance is that many children have no family history because a substantial fraction of cases are de novo, but the inheritance pattern remains autosomal dominant.
This is consistent with modern, exam-relevant references including the American Academy of Pediatrics clinical report (2019) on health supervision in NF1 and GeneReviews (continually updated), both of which characterize NF1 as autosomal dominant.
- Confusion between NF1 vs NF2 features leads learners to overthink inheritance (both are AD, but presentations differ).
- De novo cases mislead test-takers into assuming autosomal recessive.
- “Café-au-lait” triggers memorized associations (e.g., McCune-Albright, tuberous sclerosis) instead of pattern recognition.
| Option | What It Tests / Implies | Why It’s Wrong Here |
|---|---|---|
| autosomal recessive | “No family history = recessive” heuristic | NF1 is autosomal dominant; lack of family history is commonly due to **de novo** mutation, not recessive inheritance. |
| X-linked dominant | Misattribution to sex-linked transmission | NF1 affects all sexes equally and is not classically transmitted via X-linked mechanisms. |
| X-linked recessive | Confusing with XLR neurocutaneous syndromes | NF1 is not XLR; XLR patterns skew heavily male and show carrier females—doesn’t fit. |
| autosomal dominant | Correct recognition of NF1 genetics | Correct; also high-yield: variable expressivity and frequent de novo cases. |
NF1 is autosomal dominant with variable expressivity and a high de novo mutation rate—don’t let “no family history” push you to autosomal recessive.
The stem gives classic diagnostic features (multiple café-au-lait macules >5 mm in a prepubertal child plus Lisch nodules) and then tests whether you can recall the inheritance pattern without being distracted by the possibility of absent family history—an exam-favorite trap.
A 6-year-old is diagnosed with NF1 and neither parent meets diagnostic criteria. What is the most accurate counseling point?
- A. The child’s condition is autosomal recessive
- B. The condition is autosomal dominant and may be due to a de novo mutation
- C. The condition is X-linked recessive
- D. Recurrence risk is zero for all future pregnancies
- E. Only males transmit the condition
A father with clinically apparent NF1 has one child. If the mother is unaffected, what is the approximate risk the child inherits the pathogenic variant?
- A. 0%
- B. 10%
- C. 25%
- D. 50%
- E. 100%
A child has multiple café-au-lait macules and axillary freckling. Which inheritance pattern best matches the most likely diagnosis?
- A. Autosomal recessive
- B. X-linked dominant
- C. X-linked recessive
- D. Autosomal dominant
- E. Mitochondrial
A woman with mild NF1 (few café-au-lait macules only) asks about severity in her future child if inherited. Best answer?
- A. Severity is always identical within a family
- B. Severity can vary widely due to variable expressivity
- C. Children will be unaffected if the parent is mildly affected
- D. Severity depends on whether the child is male
- E. Severity is predictable from the number of café-au-lait macules in the parent
Which gene category best describes NF1?
- A. Proto-oncogene
- B. Tumor suppressor gene
- C. Mismatch repair gene
- D. Mitochondrial gene
- E. Imprinting control gene
How would your genetic counseling differ for (1) a child with NF1 and unaffected parents versus (2) a child with NF1 and an affected parent—specifically regarding recurrence risk and the concept of mosaicism?
Q1: Does “no family history” change NF1 from autosomal dominant to something else?
A1: No. The ABP/board exams expect recognition that NF1 remains autosomal dominant and often arises de novo.
Q2: Are NF1 and NF2 inherited differently?
A2: No—both are classically autosomal dominant, but their hallmark clinical findings differ (boards test phenotype distinctions more than inheritance differences).
Q3: What single phrase best describes NF1 inheritance for exams?
A3: “Autosomal dominant with variable expressivity and frequent de novo mutations.”
Q4: Why do test writers include Lisch nodules in the stem?
A4: It anchors the diagnosis to NF1 so the inheritance question becomes a direct recall/recognition task—common on pediatrics boards.
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