Alternative titles; symbols
SNOMEDCT: 717765001; ORPHA: 168984;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q26.32 | CLAPO syndrome, somatic | 613089 | 3 | PIK3CA | 171834 |
A number sign (#) is used with this entry because of evidence that CLAPO syndrome is caused by somatic mutation of the PIK3CA (171834) gene on chromosome 3q26.
Lopez-Gutierrez and Lapunzina (2008) described 6 unrelated patients with an apparently distinct syndrome of capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry of the face and limbs, and partial/generalized overgrowth. No internal or visceral abnormalities were observed. Development and mental status were normal in all patients. The parents and sibs of the patients were normal.
Rodriguez-Laguna et al. (2018) collected longitudinal data on 13 patients with CLAPO, including the 6 originally studied by Lopez-Gutierrez and Lapunzina (2008), for a total of 70.5 person-years. The mean age at diagnosis was 8.0 years. None of the patients exhibited any psychomotor delay or intellectual deficit. Among these 13 patients, the only only common clinical manifestation was the capillary malformation of the lower lip, which was present in 100%. The capillary malformation of the lower lip was always present in the midline, with a symmetrical distribution, ranging from 2 to 11 cm, with well-defined borders in several patients, and often affecting the portion of the skin under the lip or the intraoral mucosa. The second major clinical feature was the presence of lymphatic malformations, observed in 12 of 13 patients (92%). In 10 patients the lymphatic malformation involved the lip, oral mucosa, neck, and tongue, seen in 5 of 10 with right sided predominance. Another 2 patients had unilateral lymphatic malformations on the lower limbs, one of which was associated with lymphedema. At birth, the tongue had a symmetrical midline combined capillary/lymphatic/venous malformation in 8 of 13 patients with CLAPO, which was mild, well-defined, and affected the tip of the tongue. In 5 of 8 patients, the tongue lesions evolved over time, causing growth of the affected area and severe hemorrhagic events with episodes of acute inflammation. In one patient, a left thigh lymphatic malformation was not noted until 15 years of age. Asymmetry was present in 8 of 13 patients and reflected a direct consequence of the presence of a lymphatic malformation on the face and neck, although in 3 patients there was a true asymmetric overgrowth in the presence of bony hypertrophy. One patient manifested asymmetry due to left limb undergrowth. Another had macrodactyly and overgrowth of the right side of the body, and a third patient had a postnatal increase in the length of the left leg. One patient had a large presacral ganglioneuroma that required resection, and another had severe failure to thrive requiring gastrostomy.
Lopez-Gutierrez and Lapunzina (2008) considered somatic mosaicism a theoretical possibility due to patchy vascular markings of the skin and asymmetric overgrowth.
Rodriguez-Laguna et al. (2018) screened 20 paired blood and tissue DNA samples from 9 patients of a cohort of 13 patients with CLAPO and identified 5 activating mutations in the PIK3CA gene in affected tissues from 6 of the 9 patients studied. The 13 patients included the 6 patients reported by Lopez-Gutierrez and Lapunzina (2008). All mutations except 1 (F83S; 171834.0023) had been previously reported in a vascular/overgrowth disorder.
Lopez-Gutierrez, J. C., Lapunzina, P. Capillary malformation of the lower lip, lymphatic malformation of the face and neck, asymmetry and partial/generalized overgrowth (CLAPO): report of six cases of a new syndrome/association. Am. J. Med. Genet. 146A: 2583-2588, 2008. [PubMed: 18798326] [Full Text: https://doi.org/10.1002/ajmg.a.32517]
Rodriguez-Laguna, L., Ibanez, K., Gordo, G., Garcia-Minaur, S., Santos-Simarro, F., Agra, N., Vallespin, E., Fernandez-Montano, V. E., Martin-Arenas, R., del Pozo, A., Gonzalez-Pecellin, H., Mena, R., and 10 others. CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype. Genet. Med. 20: 882-889, 2018. [PubMed: 29446767] [Full Text: https://doi.org/10.1038/gim.2017.200]