Simpson-Golabi-Behmel 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.

Simpson-Golabi-Behmel syndrome is a rare genetic condition. It can occur as an inherited or de novo genetic condition, so absence of a relevant family history does not exclude the diagnosis. It is an X-linked condition and occurs predominantly in males, although females with heterozygous pathogenic variants can also be clinically affected, usually more mildly. A distinctive presentation may include the combination of generalized overgrowth, macrocephaly with characteristic coarse facies, intellectual disability, and supernumerary nipples.

It can present with psychiatric features such as ADHD, autism spectrum disorder (ASD), intellectual disability, developmental delay and language impairment. The documented neurodevelopmental and behavioural manifestations generally emerge during childhood.

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

  • Macrocephaly

  • Coarse face

  • Short neck

  • Widely spaced eyes

  • Downslanted palpebral fissures

  • Low-set ears

  • Broad nasal bridge

  • Short nose

  • Wide mouth

  • Large tongue

  • Polydactyly (of hands)

  • Syndactyly

  • Broad thumbs and/or broad halluces

  • Small nails (particularly the index finger)

Other characteristic features include congenital heart disease and conduction abnormalities; renal abnormalities including renal dysplasia, nephromegaly and duplicated renal systems; genitourinary anomalies including cryptorchidism and hypospadias; skeletal abnormalities including scoliosis, syndactyly and polydactyly; and diaphragmatic or umbilical hernia. Neurological manifestations may include hypotonia, motor and particularly speech/language delay, intellectual disability, seizures/epilepsy and abnormal EEG findings. Structural CNS abnormalities including agenesis of the corpus callosum, hydrocephalus, Chiari malformation and cerebellar vermian hypoplasia have also been reported. Other features include hepatosplenomegaly and other organomegaly. Importantly, affected individuals have an increased risk of embryonal tumours, particularly Wilms tumour and hepatoblastoma.

Early diagnosis is important to identify and manage congenital, neurological and neurodevelopmental complications; facilitate appropriate developmental, educational and psychiatric assessment and support; recognise seizures and other neurological abnormalities; permit appropriate surveillance for embryonal tumours; and guide genetic counselling and assessment of potentially affected relatives.

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.