Classic presentation occurs in affected females with widely spaced eyes, a grooved nasal tip and unilateral or bilateral coronal suture premature fusion.
As well as some variable but frequent manifestations, such as frizzy hair, cleft lip and/or palate, congenital elevation of shoulder blade (Sprengel anomaly), webbing of fingers and toes and longitudinal ridging of the nails.
Therefore, some extracranial defects have been described too, such as cardiac, abdominal and genitourinary anomalies.
Next, we present with a clinical synopsis of the clinical features:
Females:
Head
• Short and broad skull (Brachycephaly)
Face
• Frontal bossing
• Facial asymmetry
• Widow’s peak
Eyes
• Hypertelorism
• Telecanthys
• Exotropia
• Nystagmus
• Strabismus
• Downslanting palpebral fissures
• Ocular melanosis
Nose
• Bifid nasal tip
• Hypoplastic nasal tip
Mouth
• Cleft lip
• Cleft palate
Neck
• Short neck
Chest
• Narrow sloping shoulders
• Congenital elevation of shoulder blade (Sprengel deformity)
• Pectus excavatum
• Unilateral breast hypoplasia
Heart
• Atrial septal defect
• Bicuspid aortic valve
• Ventricular septal defect
• Hypertrophic cardiomyopathy
• Wolff-Parkinson-White syndrome
Abdomen
• Umbilical hernia
• Congenital diaphragmatic hernia
Genitourinary
• Uterus didephys
• Duplex kidney
• Septate vagina
Skull
• Coronal craniosynostosis (uni or bilateral)
Limbs
• Asymmetric lower limb shortness
• Joint laxity
Hands
• Webbing fingers (Syndactyly)
• Short fingers (Brachydatyly)
• Fifth finger clinodactyly
Feet
• Syndactyly
• Broad halluces
Skin
• Axillary pterygia
Nails
• Brittle nails
• Longitudinal splitting
• Grooved nails
Hair
• Thick, wiry hair
• Widow’s peak
• Low posterior hairline
Neurologic
• Developmental delay
• Floppy infant (Hypotonia)
• Hypoplasia or agenesis of corpus callosum
Males present with a less severe phenotype, sometimes showing only mild clinical features such as hypertelorism or some others, with congenital diaphragmatic hernia, but without other distinctive anomalies, as in females.
Carrier males (might present with only one of the features):
• Mild clinical features
Height
• Short stature
Head
• Brachycephaly
• Frontal bossing
• Thick, wiry hair
Face
• Hypertelorism
Hands
• Brachydactyly
Abdomen
• Congenital diaphragmatic hernia
Genitourinary
• Hypospadias
• Shawl scrotum
• Undescended testicle (Cryptorchidism)