Costello syndrome

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Costello syndrome is a rare genetic disorder. It is usually caused by a de novo pathogenic variant affecting normal cell growth and development, although inherited cases can occur. A distinctive presentation may include the combination of relative macrocephaly, coarse face, thick vermilion of the lips, nasal papillomata, loose skin over hands and feet with deep palmar and plantar creases, and hypertrophic cardiomyopathy.

It can present with psychiatric features such as anxiety, ADHD, aggression, self-injurious behavior, and behavioral dysregulation. A sociable and outgoing personality is also commonly described. Cognitive impairment, developmental delay, and speech and language impairment are common, although the degree of intellectual impairment varies. Anxiety and behavioral difficulties may persist into adulthood and warrant ongoing assessment.

From a morphologic lens perspective, other features include (but are not limited to):

  • Macrocephaly

  • Coarse face

  • Short neck

  • Epicanthus

  • Downslanted palpebral fissures

  • Low-set ears

  • Increased posterior angulation of ears

  • Large (ear)lobes

  • Depressed nasal bridge

  • Short nose

  • Thick vermilion

  • Wide mouth

  • Large tongue

  • Alveolar ridge overgrowth

  • Deep palmar creases

Other characteristic features include hypotonia, short stature, joint laxity, and skeletal abnormalities, including ulnar deviation of the wrists and fingers, tight Achilles tendons, hip dysplasia, and scoliosis or kyphosis. Cardiovascular manifestations are particularly important and include hypertrophic cardiomyopathy, pulmonic valve stenosis, and cardiac arrhythmias, particularly supraventricular tachyarrhythmias. Neurologic manifestations may include seizures/epilepsy and Chiari I malformation, with associated hydrocephalus, syringomyelia, or tethered cord in some individuals. Additional reported features include feeding difficulties, gastroesophageal reflux, constipation, obstructive sleep apnea, ophthalmologic abnormalities, hearing impairment, renal abnormalities, cryptorchidism in males, and endocrine abnormalities including growth hormone deficiency. Individuals also have a substantially increased risk of malignant tumors, including rhabdomyosarcoma, neuroblastoma, and bladder cancer.

Early diagnosis is important to identify and monitor potentially serious cardiac, oncologic, neurologic, respiratory, gastrointestinal, renal, endocrine, and developmental complications, recognize neuropsychiatric needs early, and institute tailored multidisciplinary surveillance and treatment. In particular, surveillance for malignant tumors is an important component of care during childhood, while ongoing cardiac surveillance is required because of the risk of hypertrophic cardiomyopathy and arrhythmias.

Selected references and further reading — Morphologic lens

Jones KL, Jones MC, del Campo M. Smith's recognizable patterns of human malformation. 8th ed. Philadelphia: Elsevier; 2021.

Reardon W. The bedside dysmorphologist: a guide to identifying and assessing congenital malformations. 2nd ed. Oxford: Oxford University Press; 2016.

Allanson JE, Biesecker LG, Carey JC, Hennekam RCM. Elements of morphology: introduction. Am J Med Genet A. 2009;149A(1):2-5. doi:10.1002/ajmg.a.32601.

Hennekam RCM, Biesecker LG, Allanson JE, Hall JG, Opitz JM, Temple IK, Carey JC; Elements of Morphology Consortium. Elements of morphology: general terms for congenital anomalies. Am J Med Genet A. 2013;161A(11):2726-2733. doi:10.1002/ajmg.a.36249.