midface hypoplasia

The skull has been described as brachycephalic.  The midface is flat due to maxillary hypoplasia. The lower jaw is prominent and some patients have mandibular prognathism.  A bifid uvula or partial clefting of the palate are common.  Low-set and posteriorly rotated ears have been reported as well.

 Both pectus excavatum and pectus carinatum have been described.  The teeth have dysplastic enamel and often have obliterated pulp chambers and dental cysts.  Their roots may be shortened and deformed and they are often lost early.  Vertebrae may have fusion of the spines, particularly in the cervical area.  A mixed type of hearing loss is common and some degree of intellectual disability is often evident, especially in older individuals.  Most males have some degree of hypospadias.  Cryptorchidism has been reported in one individual.

Brain imaging in one case revealed no abnormalities.

Multiple anomalies and malformations were present in the two reported patients, an unrelated male and female.  Severe facial dysmorphism secondary to uneven skull bone formation and suture closures is present.  The metopic ridge is prominent, the orbital bones are deficient, the occiput is flattened, the anterior fontanel and coronal sutures are wide.  Midfacial hypoplasia is present.  The neck is broad and the shoulders are narrow.  The fingers are long and the distal phalanges may be fixed in flexion.  The ears are low-set, small, and cupped.  The palate is high and may be cleft.  Cutaneous syndactyly of the fingers has been observed.  Variable developmental delays/learning difficulties are present.

The male had an imperforate anus, undescended testes and a 60 dB hearing loss.  The female had a midline cleft palate with choanal atresia requiring a tracheostomy from birth and required fundoplication and gastrostomy for gastroesophageal reflux.  

Arhina with anosmia is the most striking feature but it is usually accompanied by midface hypoplasia, a highly arched (or cleft) palate, and preauricular pits.  The nasal bones along with the cribriform plate, and other septal structures may be missing.  Maxillary and paranasal sinuses, together with the olfactory bulbs are often absent.  Intelligence is usually normal.

Choanal atresia is often present.  Hypogonadotropic hypogonadism with micropenis and cryptorchidism is an important feature in males.  Females may experience pubertal delay with menarche anomalies.  

Affected individuals may be of normal birth weight but skeletal growth is subnormal and there is general developmental delay.  Congenial cardiac anomalies such as persistent ductus arteriosus may be present.  Lymphedema has been noted at one year of age and probably persists throughout life.  Protein-losing enteropathy secondary to intestinal lymphangiectasia was present in one individual.  The same patient had pericardial effusion, hydrothorax, and ascites.  Intellectual disability may be severe although there is no evidence of progression.  Neurosensory hearing loss has been described in one patient.

Thrombocytopenia is a consistent finding and has been described as early as one year of age.  Platelet numbers as low as 52,000/microL have been recorded and appear larger than normal. 

The extraocular features reported so far are based on only three patients and there is considerable variation.  The head is usually small and patients may be short in stature.  The zygomatic arches, the maxillae and the mandibles are hypoplastic as is the midface.  There may be anotia and severe conductive hearing loss.  The pinnae can be large and are sometimes low-set.  Inconsistent short limbs with hip dysplasia and femoral bowing have been reported.  Brachydactyly is also a feature.