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 syndrome (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. Diagnosis
HLS can be readily diagnosed during pregnancy through the use of ultrasound, which will often reveal hydrocephaly and an abnormal structure of the brain. Precise examination via ultrasound or at birth is necessary to rule out Meckel syndrome, Trisomy 13, or Smith–Lemli–Opitz syndrome, which present with similar physiological defects. HLS can be detected at the end of the first trimester, approximately 13 weeks gestation. Treatment
No cure or treatment option for individuals with HLS currently exist.
Due to the severity of the foetal defects and the poor prognosis for those with HLS, the pregnancy is often terminated. Certain prevention can only be achieved by avoiding conception if genetic testing indicates both prospective parents as carriers of the defective HYLS1 gene. See also
•HYLS1

References


== External links ==