Alternative titles; symbols
SNOMEDCT: 699420006; ORPHA: 141148;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q26.32 | Hemifacial myohyperplasia, somatic | 606773 | 3 | PIK3CA | 171834 |
A number sign (#) is used with this entry because of evidence that hemifacial myohyperplasia (HFMH) is caused by somatic mutation in the PIK3CA gene (171834) on chromosome 3q26.
Hemifacial myohyperplasia (HFMH) is a rare cause of facial asymmetry exclusively involving facial muscles (summary by Bayard et al., 2023).
Lee et al. (2001) reported 3 patients with unilateral hyperplasia of the facial muscles with no evidence of hyperplasia of bone or other organ systems. They also identified and reviewed 6 similar cases reported by Staffenberg et al. (1998). All 9 cases had dimpling of the skin of the face secondary to hyperplastic muscle in close proximity to the dermis, pulling the skin away from the surface and resulting in dimpling. In addition, deformations of facial structures secondary to hyperplastic facial muscles, including malar flattening, auricular displacement, nasal deviation, chin deviation, narrowed palpebral fissure, and small nasal vestibule on the affected side were commonly seen. Facial nerve paralysis was also observed. Lee et al. (2001) suggested that these cases represent a distinct entity and proposed that the syndrome be called hemifacial myohyperplasia.
Pereira-Perdomo et al. (2010) reported a Colombian girl, born of unrelated parents, with hemifacial myohyperplasia. She had marked left facial asymmetry with enophthalmos, orbital dystopia, periocular asymmetry, and narrowness of the left palpebral fissure. Other features included upward deviation of the left ala of the nose, dimpling of the skin on the left side of the chin, and downward auricular displacement. Although she had facial paresis of the affected side, facial nerve conduction studies were normal. MRI and CT scan of the face showed increased thickness of the depressor anguli oris, depressor labii inferioris, orbicularis oris, zygomaticus major, buccinator, zygomaticus minor, levator labii superioris alaeque nasi, and nasalis muscles on the left side of her face. Skeletal findings included mild ipsilateral maxillary and sphenoid hypoplasia with reduced size of the bony orbit, middle skull base, and maxillary sinus.
Bayard et al. (2023) described 5 children with HFMH, aged 4 to 15 years. All of the patients had chin skin dimpling and a small nasal vestibule, 4 patients had chin deviation, an abnormal ear, and a narrow palpebral fissure, and 3 patients had nasal deviation. MRIs in the patients demonstrated muscular hypertrophy in facial, masticatory, and/or neck muscles.
Bayard et al. (2023) treated 5 patients with hemifacial myohyperplasia with alpelisib, a PIK3CA inhibitor. The patients had clinically meaningful hemifacial volume reduction with softer tissues within 3 to 4 weeks of treatment.
In a review of the possible etiology of HFMH, Pereira-Perdomo et al. (2010) suggested that it is a primary disorder of somitomeric myoblasts occurring around the fourth gestational week, when these muscle progenitor cells are located at the cranial somitomeres or branchial arches. There is likely an imbalance between differentiation and proliferation of the myoblasts due to abnormal signaling patterns, resulting in muscle hyperplasia in a select area. This region selectivity likely reflects somatic mosaicism. Bony and nerve abnormalities, when present, are likely secondary to abnormal muscle tone and function.
By genotyping of affected muscle tissue from 5 patients with hemifacial myohyperplasia, Bayard et al. (2023) identified mosaic mutations in the PIK3CA gene (606773). Patients 1 and 5 had mosaicism for a glu545-to-lys mutation (E545K; 171834.0003), with mutation burdens of 15% and 14%, respectively. Patients 3 and 4 had mosaicism for a glu542-to-lys mutation (E542K; 171834.0009), with mutation burdens of 12% and 21%, respectively, and patient 2 had mosaicism for a his1047-to-arg mutaton (H1047R; 171834.0013), with a mutation burden of 25%.
Bayard, C., Segna, E., Taverne, M., Fraissenon, A., Hennocq, Q., Periou, B., Zerbib, L., Ladraa, S., Chapelle, C., Hoguin, C., Kaltenbach, S., Villarese, P., and 19 others. Hemifacial myohyperplasia is due to somatic muscular PIK3CA gain-of-function mutations and responds to pharmacological inhibition. J. Exp. Med. 220: e20230926, 2023. [PubMed: 37712948] [Full Text: https://doi.org/10.1084/jem.20230926]
Lee, S., Sze, R., Murakami, C., Gruss, J., Cunningham, M. Hemifacial myohyperplasia: description of a new syndrome. Am. J. Med. Genet. 103: 326-333, 2001. [PubMed: 11746014]
Pereira-Perdomo, D. F., Velez-Forero, J., Prada-Madrid, R. Hemifacial myohyperplasia sequence. Am. J. Med. Genet. 152A: 1770-1773, 2010. [PubMed: 20583183] [Full Text: https://doi.org/10.1002/ajmg.a.33428]
Staffenberg, D. A., McCarthy, J. G., Hollier, L. H., Grayson, B. H., Verdi, G. Hypertrophy and asymmetry of the facial muscles: a previously unrecognized association. Ann. Plast. Surg. 40: 533-537, 1998. [PubMed: 9600442] [Full Text: https://doi.org/10.1097/00000637-199805000-00017]