# Neurofibromatosis

> Neurofibromatosis for NEET-PG Dermatology covering NF1 versus NF2 diagnostic criteria, cafe-au-lait macules, neurofibromas, Lisch nodules and the key cutaneous signs.

- Canonical URL: https://prepelephant.com/topics/neet-pg/dermatology/neurofibromatosis
- Exam / course: NEET-PG · Subject: Dermatology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-08
- Last updated: 2026-10-08
- Reference basis: Rook's Textbook of Dermatology; Fitzpatrick's Dermatology; Nelson Textbook of Pediatrics
- How to cite: "Neurofibromatosis", PrepElephant, https://prepelephant.com/topics/neet-pg/dermatology/neurofibromatosis

## Direct answer

Neurofibromatosis comprises autosomal dominant disorders of nerve sheath tumour formation, the commonest being neurofibromatosis type 1 caused by NF1 mutations on chromosome 17. Diagnosis of NF1 rests on the NIH criteria, which need two or more of seven features, including six or more café-au-lait macules, two or more neurofibromas and two or more Lisch nodules. Neurofibromatosis type 2 instead produces bilateral vestibular schwannomas due to NF2 mutations on chromosome 22.

## What you must remember

- **NF1 gene:** located on chromosome 17q11.2 and encoding neurofibromin, a RAS-GTPase activating protein; about half of cases arise de novo.
- **Café-au-lait macules:** six or more, over 5 mm before puberty or over 15 mm after puberty; they are the commonest early sign.
- **Neurofibromas:** dermal neurofibromas are soft, with a buttonhole sign on pressure, while plexiform neurofibromas feel like a bag of worms and carry a risk of malignant change.
- **Lisch nodules:** iris hamartomas seen on slit lamp examination; two or more count as a diagnostic criterion.
- **Axillary and inguinal freckling:** also called the Crowe sign, usually appearing in childhood.
- **NF2 gene:** chromosome 22q12, encoding the tumour suppressor merlin; it causes bilateral vestibular schwannomas, meningiomas and juvenile posterior subcapsular cataracts.
- **Malignancy:** malignant peripheral nerve sheath tumours, optic pathway glioma and pheochromocytoma are NF1 associations to know.

## NF1 and NF2 side by side

The two main types share a name but differ in gene, tumours and skin signs, which is how exam stems separate them. Use the table to match the stem to the correct type.

| Feature | NF1 | NF2 |
|---|---|---|
| Gene and chromosome | NF1, 17q11.2 | NF2, 22q12 |
| Protein | Neurofibromin | Merlin |
| Hallmark skin signs | Café-au-lait macules, neurofibromas | Few skin signs; cutaneous schwannomas |
| Eye feature | Lisch nodules, optic glioma | Posterior subcapsular cataract |
| Typical tumour | Neurofibromas, optic glioma | Bilateral vestibular schwannomas |
| Hearing | Usually normal | Progressive hearing loss |

Multiple café-au-lait macules with Lisch nodules point to NF1, whereas bilateral vestibular schwannomas with cataract point to NF2. Both are autosomal dominant with variable expression, so a family history helps but is not always present.

## Where the criteria and tumours mislead

Most mistakes come from counting features wrongly or assigning a tumour to the wrong gene.

- **Trap:** diagnosing NF1 from a single café-au-lait macule. **Correct:** six or more macules of the stated size are needed, because a single patch is common in the general population.
- **Trap:** calling bilateral acoustic neuromas NF1. **Correct:** bilateral vestibular schwannomas define NF2, which has a different gene and prognosis.
- **Trap:** treating a plexiform neurofibroma as benign whatever its behaviour. **Correct:** rapid growth, pain or neurological change should prompt imaging, since malignant transformation can occur.
- **Trap:** missing Lisch nodules because no ophthalmic examination was done. **Correct:** slit lamp examination of the iris is part of NF1 assessment.

## Frequently asked questions

### How many café-au-lait macules suggest NF1?

Six or more café-au-lait macules suggest NF1, measuring over 5 mm in prepubertal children and over 15 mm after puberty. A single patch is common in the general population, so the count and size matter for diagnosis.

### What is a Lisch nodule and why does it matter?

Lisch nodules are benign iris hamartomas seen on slit lamp examination and are a common feature of neurofibromatosis type 1. Two or more Lisch nodules count as one of the seven NIH diagnostic criteria for NF1.

### Which gene is mutated in neurofibromatosis type 2?

Neurofibromatosis type 2 is caused by mutations in NF2 on chromosome 22q12, which encodes the tumour suppressor merlin. It produces bilateral vestibular schwannomas, meningiomas and juvenile cataracts.

### What is a plexiform neurofibroma?

A plexiform neurofibroma is a diffuse, tortuous nerve tumour that feels like a bag of worms and is characteristic of neurofibromatosis type 1. It can cause disfigurement and carries a risk of malignant peripheral nerve sheath tumour.

### What is the buttonhole sign?

The buttonhole sign describes a dermal neurofibroma that herniates through a gap in the subcutaneous tissue when pressed, feeling soft and compressible. It is a classic bedside sign in neurofibromatosis type 1.