FaCD Online Syndrome Fact Sheet

Last updated: 19 Apr 2011

Name: Costello syndrome

Synonym: incl.: Facio-Cutaneous-Skeletal syndrome

Mode of Inheritance: de novo

Genes

HRAS, mapped to 11p15.5

Tumor features

cutaneous syringoma
facial papules
fibrosarcoma
neuroblastoma, adrenal
rhabdomyosarcoma
urinary bladder cancer

Tumor features (possible)

ganglioneuroblastoma
gastric polyps
vestibular schwannoma

Non-tumor features

acanthosis nigricans
brachydactyly, of hands
brushfield spots of the iris
developmental delay/mental deficiency/mental retardation
ears, large fleshy lobes of
ears, low-set
epicanthal folds
growth deficieny
hyperkeratosis
hyperpigmentation of the skin
keratoconus
mouth, large (macrostomia)
myocardial disease
nails, small, dysplastic
nasal bridge, depressed
neck, short
nevi
palpebral fissures, downward slanting
polyhydramnion
simian crease
skin, redundant
strabismus
thorax, large

Non-tumor features (possible)

cataract

Comment

This syndrome is characterized by postnatal growth deficiency, cardiomyopathy, (mild to moderate) mental deficiency, redundant skin on neck, palms and soles, skin hyperpigmentation, acanthosis nigricans, papillomata, resembling verruca vulgaris and typically located on the nose, periorally and on trunk and limbs. Laryngeal papillomata may occur. Typical craniofacial dysmorphisms are present and there is clinical and molecular overlap with CFC syndrome[1-5].

Tumors (in addition to the papillomata) have been reported in some cases: ganglioneuroblastoma[2;6], epithelioma[4], alveolar rhabdomyosarcoma of the foot[7] and retroperitoneal embryonal rhabdomyosarcoma (3 cases[5;8]), gastric fibroid polyp in a 4-month-old girl[15]. Transitional cell cancer of the bladder was reported in a 11-year-old boy [9] and a 14-year-old girl[10] with Costello syndrome. Suri and Garret[11] observed a vestibular schwannoma and cataract (both of which can be found in NF2) in a 33 year old patient with Costello syndrome.
Gripp reviewed the occurrence of cancer in Costello syndrome: the most common tumor in CS is rhabdomyosarcoma (RMS), followed by neuroblastoma and bladder carcinoma[12]. Kratz et al updated this review[16]: 19 cases of rhabdomyosarcoma, 5 of neuroblastoma, 4 of childhood-onset bladder cancer and 1 fibrosarcoma have been published in the literature so far.

HRAS protooncogene mutations cause this syndrome[13,14].

References

[1] Philip N, Sigaudy S. Costello syndrome. J Med Genet 1998; 35:238-240.
[2] Zampino G, Mastroiacovo P, Ricci R, Zollino M, Segni G, Martini-Neri ME, Neri G. Costello syndrome: further clinical delineation, natural history, genetic definition, and nosology. Am J Med Genet 1993; 47:176-183.
[3] Der Kaloustian VM, Moroz B, McIntosh N, Watters AK, Blaichman S. Costello syndrome. Am J Med Genet 1991; 41:69-73.
[4] Martin RA, Jones KL. Delineation of the Costello syndrome. Am J Med Genet 1991; 41:346-349.
[5] Kerr B, Eden OB, Randamudi R, Shannon N, Quarrell O, Emmerson A, Ladusans E, Gerrard M, Donai D. Costello syndrome: two cases with embryonal rhabdomyosarcoma. J Med Genet 1998; 35:1036-1039.
[6] Moroni I, Bedeschi F, Luksch R, Casanova M, D' Incerti L, Uziel G, Selicorni A. Costello Syndrome: a cancer predisposing syndrome? CLINICAL DYSMORPHOLOGY 2000; 9(4):265-268.
[7] Feingold M. Costello syndrome and rhabdomyosarcoma. J Med Genet 1999; 36:582-583.
[8] Philip NM, Sigaudy S, Lacombe D, Vittu G, David A, Vigneron J, Monica A. Costelle syndrome: report of eight patients including one with a rhabdomyosarcoma. Am J Hum Genet 65[4], A338. 1999. Ref Type: Abstract
[9] Franceschini P, Licata D, Di Cara G, Guala A, Bianchi M, Ingrosso G, Franceschini D. Bladder carcinoma in Costello syndrome: report on a patient born to consanguineous parents and review. Am J Med Genet 1999; 86(2):174-179.
[10] Gripp KW, Scott CIJ, Nicholson L, Figueroa TE. Second case of bladder carcinoma in a patient with Costello syndrome. Am J Med Genet 2000; 90:256-259.
[11] Suri M, Garrett C. Costello syndrome with acoustic neuroma and cataract. is the Costello locus linked to neurofibromatosis type 2 on 22q? Clin Dysmorph 1998; 7:149-151.
[12] Gripp KW. Tumor predisposition in Costello syndrome. American journal of medical genetics. Part C, Seminars in medical genetics 2005; 137(1):72-7.
[13] Kerr B, Delrue MA, Sigaudy S, Perveen R, Marche M, Burgelin I, Stef M, Tang B, Eden OB, O'Sullivan J, De Sandre-Giovannoli A, Reardon W, Brewer C, Bennett C, Quarell O, M'Cann E, Donnai D, Stewart F, Hennekam R, Cavé H, Verloes A, Philip N, Lacombe D, Levy N, Arveiler B, Black G. Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases. Journal of medical genetics 2006; 43(5):401-5.
[14] Rauen KA. HRAS and the Costello syndrome. Clinical genetics 2007; 71(2):101-8.
[15] Campus R, Di Rocco M, Sementa AR, Senes FM, Magillo P, Dodero P. [Gastric fibroid polyp in a 4-month-old girl with Costello syndrome]. Pediatr Med Chir. 2007 Sep-Oct;29(5):267-9.
[16] Kratz CP, Rapisuwon S, Reed H, Hasle H, Rosenberg PS. Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes. Am J Med Genet C Semin Med Genet. 2011 Apr 15.[Epub ahead of print].