Classic presentation occurs in heterozygous females with midline defects, as severe hypertelorism, a grooved nasal tip and unilateral or bilateral coronal craniosynostosis.
As well as some variable but frequent manifestations, such as frizzy hair, cleft lip and/or palate, Sprengel anomaly, partial syndactyly of the hands and feet and longitudinal ridging of the nails.
Therefore, some extracranial not midline defects have been described too, as they might present with cardiac, abdominal, and genitourinary anomalies as well.
Females:
Head
• Brachycephaly
• Plagiocephaly
Face
• Frontal bossing
• Facial asymmetry
• Widow’s peak
Eyes
• Hypertelorism
• Telecanthus
• Exotropia
• Nystagmus
• Strabismus
• Downslanting palpebral fissures
• Ocular melanosis (one patient)
Nose
• Bifid nasal tip
• Hypoplastic nasal tip
Mouth
• Cleft lip
• Cleft palate
Neck
• Short neck
Chest
• Narrow sloping shoulders
• Sprengel deformity
• Scoliosis
• 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 didelphys
• Duplex kidney
• Septate vagina
Skull
• Coronal craniosynostosis (uni or bilateral)
Limbs
• Asymmetric lower limb shortness
• Joint laxity
Hands
• Syndactyly
• Brachydactyly
• 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
• Hypotonia
• Hypoplasia or agenesis of corpus callosum
Males present with a less severe phenotype, sometimes showing only mild clinical features such as hypertelorism. Some others, present with congenital diaphragmatic hernia, but without other distinctive anomalies, as in females.
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
• Cryptorchidism