Deletion 4p syndrome (Wolf-Hirschhorn 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.

Deletion 4p syndrome (Wolf-Hirschhorn syndrome) is a rare chromosomal disorder caused by deletion of genetic material from the short arm of chromosome 4. It usually occurs as a de novo chromosomal change, although some cases result from an inherited parental chromosome rearrangement, so absence of a relevant family history does not exclude the diagnosis. It occurs more commonly in females than males. A distinctive presentation may include widely spaced eyes, broad nasal bridge, microcephaly and/or cranial asymmetry, and low-set, simple ears, sometimes with preauricular pits.

It can present with psychiatric features such as ADHD and behavioural difficulties. Autism spectrum disorder (ASD) has also been described, although the evidence for a specific association remains limited. Neurobehavioural manifestations are usually recognised during childhood, although behavioural and social difficulties may persist into adolescence and adulthood.

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

  • Microcephaly

  • Micrognathia

  • Widely spaced eyes

  • Epicanthus

  • Preauricular tag or pit

  • Short philtrum

  • Downturned corners of mouth

  • Single transverse palmar crease

Other characteristic features include developmental delay or intellectual disability, hypotonia, seizures, and significant speech and language impairment. Structural neurological abnormalities may include corpus callosum abnormalities, ventricular enlargement, and other brain malformations. Other important manifestations include prenatal and postnatal growth restriction, skeletal abnormalities, congenital heart defects, hearing impairment, renal or urinary tract abnormalities, feeding difficulties, and ocular abnormalities.

Early diagnosis is important to identify and manage potentially significant neurological, developmental, growth, feeding, cardiac, auditory, renal, and other congenital complications; to establish appropriate seizure management and developmental support; and to provide coordinated multidisciplinary care.

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.