Au-Kline syndrome (HNRNPK-related neurodevelopmental disorder; Kabuki-like phenotype)

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.

Au-Kline syndrome (HNRNPK-related neurodevelopmental disorder; Kabuki-like phenotype) is a rare genetic disorder. It is generally inherited in an autosomal dominant manner, with most cases resulting from a de novo pathogenic variant, although inherited cases can occur. The phenotype may resemble Kabuki syndrome, particularly in its characteristic facial features and neurodevelopmental impairment, but these conditions are genetically distinct. A distinctive presentation may include the combination of ptosis with long palpebral fissures, long thumbs and/or great toes, and genitourinary anomalies. The limb and genitourinary features may help distinguish Au-Kline syndrome from Kabuki syndrome.

It can present with psychiatric features such as autism spectrum disorder (ASD), ADHD or hyperactivity, anxiety, behavioral dysregulation, repetitive behaviors, and sleep disturbance. Cognitive impairment, developmental delay, and speech and language impairment are common, with expressive language often particularly affected. Social and behavioral difficulties may be prominent, although the neuropsychiatric phenotype remains incompletely characterized. These manifestations generally emerge during childhood or development, although behavioral and neuropsychiatric difficulties may persist into adulthood and require ongoing assessment and support.

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

  • Microcephaly

  • Prominent forehead

  • Epicanthus

  • Broad nasal bridge

  • Bulbous nose

  • Low-set ears

  • Clinodactyly of fifth fingers

  • Single transverse palmar crease

Other characteristic features include hypotonia, growth abnormalities, and skeletal abnormalities. Neurologic manifestations may include seizures/epilepsy and structural brain abnormalities, including abnormalities of the corpus callosum. Ophthalmologic manifestations may include strabismus and refractive errors, while hearing impairment may also occur. Additional reported features include congenital heart defects, renal and genitourinary abnormalities, gastrointestinal and feeding difficulties, constipation, recurrent respiratory infections, dental abnormalities, and genital abnormalities.

Early diagnosis is important to identify and monitor potentially serious neurologic, cardiac, renal, gastrointestinal, auditory, ophthalmologic, and developmental complications, recognize neuropsychiatric needs early, and institute tailored multidisciplinary surveillance and treatment.

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.