Miller-Dieker syndrome (Lissencephaly 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.

Miller-Dieker syndrome (lissencephaly syndrome) is a rare genetic condition. It usually occurs as a de novo genetic condition, although it can occasionally result from an inherited chromosomal rearrangement; therefore, absence of a relevant family history does not exclude the diagnosis. A distinctive presentation may include the combination of severe developmental and intellectual impairment, microcephaly, characteristic facial features, early-onset seizures, and lissencephaly on brain imaging.

It can present with psychiatric features such as behavioural difficulties, autistic features, agitation and sleep disturbance. However, the available literature is limited regarding discrete psychiatric diagnoses, and the severe intellectual disability and neurological impairment characteristic of the syndrome can substantially influence behavioural and psychiatric presentation. The neurodevelopmental manifestations generally emerge in infancy or early childhood, and late-onset psychiatric presentations in adulthood are not characteristic.

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

  • Microcephaly

  • Micrognathia

  • Upslanted palpebral fissures

  • Low-set ears

  • Short nose

  • Clinodactyly of fifth fingers

Other characteristic features include classic lissencephaly, characterised by absent or markedly reduced normal cerebral gyration (agyria or pachygyria) resulting from abnormal neuronal migration during brain development. Neurological manifestations include severe developmental delay and intellectual disability, hypotonia, impaired motor development and early-onset seizures, which may be frequent and difficult to control; abnormal EEG findings are common. Growth retardation, including poor growth, failure to thrive and microcephaly, is also common. Other structural brain abnormalities may include ventriculomegaly and hypoplasia of the corpus callosum. Additional congenital abnormalities can include cardiac defects, renal and urogenital abnormalities, and gastrointestinal abnormalities such as omphalocele. Feeding and swallowing difficulties are common and may contribute to aspiration and recurrent respiratory complications. The severity of the neurological phenotype is substantial, with most affected individuals having severe to profound intellectual disability and markedly reduced life expectancy, although some individuals survive into adolescence or adulthood.

Early diagnosis is important to identify and manage seizures and other neurological complications; recognise feeding, swallowing and respiratory problems; assess for associated congenital abnormalities; provide appropriate developmental, educational and psychiatric assessment and support; and facilitate genetic counselling and recurrence-risk assessment for the family.

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.