The pathophysiology of HLS is abnormal cilia development arising from the inability of the mutated HYLS1 gene to correctly target centrioles to the plasma membrane. Specifically, transition fibres within the transition zone, at the base of the axoneme and adjoining to the plasma membrane, lack proper development. As these structures form the cilial gate, improper development results in a loss of selectivity for protein entry into the ciliary compartment. Variations and related pathologies Mutations in KIF7 have also been noted in patients that present a similar phenotype to HLS and the characteristic HYLS1 A to G transformation; homozygous deletion of the KIF7 gene causes a variant form of HLS, HLS2. KIF7 encodes a structural factor vital to cilial transport, and is also implicated in other developmental disorders, such as Joubert<unk>  (JS). Additionally, mutations in HYLS1 are no longer explicitly connected to HLS in humans. Homozygous mutations removing the stop codon in exon 4 of HYLS1 result in a different genomic sequence disruption to the missense mutation of HLS, and phenotypically present as JS. The ‘molar tooth sign’ of the brain, an anomaly in which cerebellar volume is reduced but cerebellar shape is retained, resembles the molar tooth and is used to identify JS. JS presents with mutations in more than 30 genes, whilst the HYLS1 mutation is the sole cause of HLS, but is also present in the HLS2 variant form with the mutated KIF7 gene.
Hydrolethalus syndrome
Gray baby syndrome
Cantú syndrome
Neonatal encephalopathy
Blue baby syndrome
Foster Kennedy syndrome
Muenke syndrome
Baboon syndrome