The clinical features of this disease, per organ system, include:
Central Nervous System
- Global developmental delay
- Intellectual disability
- Speech delay
- Motor delay
- Generalized hypotonia (some patients)
- Truncal hypotonia (some patients)
- Appendicular hypertonia (some patients)
- Brisk reflexes
- Ankle clonus
- Learning disability
- Seizures (rare)
- Brain abnormalities (some patients):
- Symmetrical restricted diffusion
- High T2 signal intensity of the cerebral white matter and dentate nucleus
- Chiari malformation
- Delayed myelination
Head and Neck
- Macrocephaly (some patients)
- Microcephaly (rare)
- Dysmorphic facial features, including:
- Triangular face
- Short forehead with low anterior hairline (rare)
- Pointed chin
- Dysmorphic ears
- Low-set ears
- Prominent ear lobes
- Posteriorly rotated ears
- Depressed nasal bridge
- Anteverted nares
- Broad nasal bridge
- Thin upper lip
- Smooth philtrum
- Short philtrum (rare)
- Long philtrum
- Hypertelorism
- Deep-set eyes
- Upslanted palpebral fissures
- Strabismus
- Synophrys
- Thick, arched eyebrows
- Webbed neck (rare)
- Long eyelashes (some patients)
- Myopia (rare)
- Optic glioma (rare)
Cardiovascular
- Patent foramen ovale
- Patent ductus arteriosus
- Atrial septal defect
- Ventricular septal defect
- Pulmonary hypoplasia
- Pulmonary atresia
- Tetralogy of Fallot
- Double outlet right ventricle
Skeletal
- Scoliosis
- Long fingers and toes
- Overlapping fingers and toes
- Cutaneous syndactyly of the toes
- Large hands
- Pectus excavatum (some patients)
Genitourinary
- Cryptorchidism
- Hypospadias
- Late menarche
- Oligomenorrhea
Other
- Somatic overgrowth
- Hypertrichosis
- Widely spaced nipples
- Recurrent respiratory infections
- Dilation of ascending aorta
- Intraosseous hemangioma
- Intestinal malrotation
- Inguinal hernia
- Omphalocele