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Start free with EleplanNeurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome
ORPHA:453499Malformation syndrome
Also called Au-Kline syndrome · HNRNPK-related neurodevelopmental disorder · Okamoto syndrome
What it is
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, hypotonia, craniofacial dysmorphism (such as ridged metopic sutures, long palpebral fissures, broad nasal bridge, hypoplastic alae nasi, low-set, prominent ears, prominent midline tongue groove, and downturned mouth), congenital heart defects, and variable skeletal abnormalities including hip dysplasia, vertebral anomalies, and scoliosis. Additional reported manifestations include high pain tolerance and genitourinary anomalies. Brain imaging may show a thin corpus callosum or white matter abnormalities.
Key facts
- Prevalence
- <1 / 1 000 000
- Age of onset
- Antenatal, Infancy, Neonatal
- Inheritance
- Autosomal dominant, Not applicable
- Classified as
- Malformation syndrome
Prevalence figures describe populations, not individuals, and are often estimates from a single study. Where the figure is an incidence or a birth prevalence, it says so.
Signs and symptoms
Very common80–99%
13Common30–79%
29- Abnormal autonomic nervous system physiology
- Cleft palate
- Constipation
- Craniosynostosis
- Cryptorchidism
- Downturned corners of mouth
- Failure to thrive
- Furrowed tongue
- Gastroesophageal reflux
- Gastrointestinal dysmotility
- Hearing impairment
- High palate
- Hip dysplasia
- Hypoplasia of the corpus callosum
- Increased nuchal translucency
- Intrauterine growth retardation
- Inverted nipples
- Microcephaly
- Open mouth
- Prominent metopic ridge
- Ptosis
- Reduced tendon reflexes
- Scoliosis
- Shallow orbits
- Talipes
- Underdeveloped nasal alae
- Ventricular septal defect
- Vertebral segmentation defect
- Vesicoureteral reflux
These ranges are how often a sign appears across everyone diagnosed, not a prediction for one person — most people have some of these and not others. Orphanet also records findings that are specifically absent in this disease; those are in the data but not listed here.
Genes reported in subtypes
Orphanet records this gene on 2 more specific entries under this disorder, not on this entry itself:
A well-studied disease is usually split into subtypes, and the gene is curated on whichever one the evidence belongs to. Open a subtype to see which gene goes with it.
ICD-10 codes
ICD-10 has no distinct code for most rare diseases, so many are filed under the nearest available one. A shared code identifies the group, not this disease — the ORPHAcode above is what identifies it.
Related health topics
Reached through the ICD-10 categories this disease is filed under, so these describe the broader group rather than this disease specifically.
Cross-references
Orphadata Science: Free access data from Orphanet. © INSERM 1999. Data version 2026-06-23. Available under CC BY 4.0. This is a reference, not medical advice.
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