pilomatrixoma and genetic testing

Pilomatrixoma and Genetic Testing

Anyone studying pilomatrixomas will discover they can be associated with a variety of conditions. 

  • Turner syndrome
  • Gardner syndrome
  • Myotonic dystrophy

are the most common three mentioned, but there are a whole host of others reported (usually as isolated case reports) – Rubinstein-Taybi, Sotos, Stickler, Kabuki syndromes; Trisomies 19 and 9; xeroderma pigmentosum; basal cell naevus Syndrome; sarcoidosis.

The question arises – who to consider referring for genetic testing? Many papers casually mention ‘multiple’ pilomatrixomas being associated with syndromes, but don’t say how often they’re associated or just how many constitutes ‘multiple’ . About 3.5% of cases of pilomatrixoma will have more than one. On one hand you don’t want to miss the chance to diagnose an associated condition earlier than it would have otherwise become apparent. On the other hand you don’t want to unnecessarily worry large numbers of families by referring every child with more than one pilomatrixoma. Most people wouldn’t consider referring a child with a single pilomatrixoma for genetic testing. Some balance is required.

pilomatrixoma and genetic testing

There is a recent paper tackling this question. 1 Thee authors suggest referral for genetic screening in the following circumstances

  • 6 or more pilomatrixomas
  • 1 in the setting of a family history of myotonic dystrophy, 1st-degree relative with colon cancer or FAP-related syndrome, or family history of pilomatrixomas
  • 1 in the setting of a clinical features suggestive of Turner or Rubenstein-Taybi syndromes.

Including a recommendation for screening if a 1st-degree relative had colon cancer doesn’t narrow it down very much. And why did they decide on 6 or more? If you gather the extant literature on cases with multiple pilomatrixomas, and include those with associated conditions (as these authors did), you can work out the sensitivity and specificity, &c of using various numbers. These are their data, based on 6 or more pilomatrixomas using that cutoff to look for myotonic dystrophy, FAP-related diseases, Turner, and Rubenstein-Taybi syndromes:

Sensitivity (%) (95% CI) 46.30 (32.62-60.39)
Specificity (%) (95% CI) 95.52 (90.51-98.34)
Positive Predictive Value (%) (95% CI) 80.65 (64.43-90.55)
Negative Predictive Value (%) (95% CI) 81.53 (77.46-85.01)

So, using 6 as your cutoff will have a false positive rate of just under 5% – that’s good if you want to avoid distressing families. But the sensitivity is under 50%, so you’ll detect less than half of all cases. Each time you refer someone, or not, there’s an 80% chance you’ve done the right thing for that patient.

What happens if you refer everyone with 2 or more pilomatrixomas?

There are 214 cases in the literature with 2 or more, 54 of them (~25%) had an underlying genetic condition. Here are the numbers:

Association with multiple PM 2-5 (%) 6-9 (%) 10 (%) Total
Myotonic dystrophy 20 (58.8) 4 (11.8) 10 (29.4) 34
FAP-related syndromes 2 (33.3) 1 (16.7) 3 (50.0) 6
Turner syndrome 3 (33.3) 4 (44.4) 2 (22.2) 9
Rubenstein-Taybi syndrome 4 (80) 0 (0.0) 1 (20.0) 5
Total syndromic 29 (53.7) 9 (16.7) 16 (29.6) 54
Total familial 21 (80.8) 5 (19.2) 0 (0.0) 26
Total sporadic 128 (95.5) 3 (2.2) 3 (2.2) 134
Total 178 (83.2) 17 (7.9) 19 (8.9) 214

So you can essentially decide for yourself where your cutoff should lie, and how many you’re prepared to miss in order not to distress, or vice versa.

Personally, I’m comfortable with “six, or suspicious”. In other words, all patients with six or more, or if I think something’s up with smaller numbers. To do that I’ve had to re-read the features of all of the associated conditions, in particular how they look in the early phases.


1 Ciriacks K, Knabel D, Waite MB. Syndromes associated with multiple pilomatricomas: When should clinicians be concerned? Pediatric Dermatology 2020; 37: 9–17.

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