A curable cause of facial asymmetry

Genodermatosis

Dr. Emmanuelle Bourrat

Saint-Louis Hospital

The clinical case
Now it's your turn!
Co-prescription and advice

Clinical case presentation

An adolescent presented with a congenital condition involving swelling of the left hemiface, associated with pigmented spots.

The dermatological examination revealed:

- Hypertrophy of the left hemiface, predominantly the cheek.

- Linear Blaschko pigmented lesions, discreetly papular (“velvety” appearance on palpation), all over the left hemiface.

The rest of the cutaneous and extracutaneous examination was strictly normal. Discomfort was exclusively cosmetic. MRI confirmed that the hypertrophy had developed from fibroadipose tissue and that there was no indication for surgery; skin biopsy showed that the linear Blaschko lesions were epidermal hamartoma.

Your turn

What is your diagnosis?

Select 1 answer(s) from the following choices:

Plexiform neurofibroma in NF1

Body asymmetry associated with Necker’s nevus

Beckwith-Wiedemann syndrome

PROS (PIK3CA-related overgrowth syndrome)

Wrong answer!

Good answer!

Selected diagnosis

The diagnosis is PROS (PIK3CA-related overgrowth syndrome). This diagnosis is confirmed by the demonstration of an activating mutation (gain of function) of the PIK3CA gene in mosaic form (absence in blood cells) in the skin biopsy of the hamartoma.

PROS is a group of rare diseases within which three major subtypes can be distinguished depending on the tissue in which the excess cell growth predominates.

The term CLOVES stands for “Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/Skeletal/Spinal anomalies” and the picture is often dominated by segmental hypertrophy (focal or plurifocal).
The term Klippel-Trenaunay (KTS) is used when vascular malformations, often in the foreground, are associated with soft tissue and bone tissue hypertrophy and affect one limb, most often the lower limb.
The term MCAP will be used for Megalencephaly-capillary malformation-polymicrogyria when the picture is dominated by cerebral hypertrophy (megalencephaly).
In our patient, the combination of facial hypertrophy and epidermal hamartoma led to the more precise diagnosis of CLOVES.

Explanation of wrong answers

Differential diagnoses:

1) NF1 is ruled out, as the café-au-lait spots are neither papular nor blaschkolinear and the MRI appearance of the plexiform neurofibroma is typical.

2) Large Becker’s nevus may be associated with hypotrophy (particularly of the breast) adjacent to the lesion but not with hypertrophy at a distance.

3) Beckwith-Wiedemann syndrome is a genetic syndrome that associates body hypertrophy, macroglossia, multiple congenital malformations, neonatal hypoglycemia and tumor predisposition but no epidermal hamartoma.

Treatment

Treatment with a PIK3CA inhibitor was therefore proposed.

Message from the expert

When congenital tissue hypertrophy is detected, the opinion of a dermatologist is essential: it can help guide the diagnosis towards a PROS, especially in the case of associated skin lesions suggestive of mosaics (vascular, epidermal, lipomatous hamartomas etc.).

References :

^{PNDS PROS syndrome without cerebral involvement published on the HAS website 2020}