Table 3. Typical clinical, imaging and genetic characteristics of specific MBHB malformations primarily involving the brainstem*.
| Disorder | Clinical features | Imaging features | Causes/testing | Inheritance |
|---|---|---|---|---|
| HGPPS | Scoliosis, horizontal gaze palsy Normal NDV outcome |
Brain: Dorsal midline cleft leads to “butterfly” appearance of pons, medulla Spine: early and progressive scoliosis |
ROBO3 | AR |
| Duane retraction syndrome, Duane radial ray syndrome |
CHN1 mutations Limited eye adduction with globe retraction and palpebral fissure narrowing SALL4 mutations Radial ray abnormalities (thenar hypoplasia, thumb hypoplasia/aplasia, triphalangeal thumb, shortened forearm, preaxial polydactyly), kidney malformations, coloboma, cardiac malformations (rare), hearing loss Normal NDV outcome |
Hypoplastic/absent abducens nerve, likely other oculomotor nerve defects | CHN1, SALL4 | AD (SALL4, ∼50% de novo) |
| Athabaskan brainstem dysgenesis and Bosley-Salih-Alorainy syndromes | Cranial nerve palsies, sensorineural hearing loss, abnormal intracranial blood vessels and cardiac outflow tract defects | No published brain imaging abnormalities | HOXA1A | AR |
| Moebius syndrome | Facial palsy with impaired ocular abduction (variable involvement of other cranial nerves) Variable somatic malformations Variable NDV outcome |
Heterogeneous: hypoplastic brainstem with calcifications, hypoplastic or absent cranial nerves | Misoprostol exposure in utero, TUBB3, HOXA1A and HOXB1 mutations in patients with Moebius features | Sporadic (rarely AD and AR) |
| Diencephalic–mesencephalic junction dysplasia | Progressive microcephaly, spasticity, intellectual disability, seizures | rostral-caudal shortening and dorsal-ventral lengthening of the midbrain, deep interpeduncular cistern Variable features: cortical calcifications, agenesis of the corpus callosum, ventriculomegaly, brainstem dysplasia and cerebellar vermis hypoplasia |
Unknown | AR |
*
Note that information published for many of the disorders is quite limited, so the full spectrum of characteristics is likely broader than depicted in this table.