Abstract
Joubert syndrome (JBTS) is a rare ciliopathy characterized by developmental delay, hypotonia, and distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). We reported a 15-month-old female with dysmorphic features (flat nasal bridge, almond-shaped eye, and a minor midline notch in the upper lips), hypotonia, polydactyly, development delay, and MTS. Whole exome sequencing revealed biallelic heterozygous mutations c.535C>G(p.Q179E/c.853G>T) (p.E285*) in IFT74, which were inherited from the parents. So far, only one article reported JBTS associated with IFT74 gene mutation, and this is the second report of the fifth patient with JBTS due to variants in IFT74. All five patients had developmental delay, postaxial polydactyly, subtle cleft of the upper lip, hypotonia, and MTS, but notably without renal and retinal anomalies or significant obesity, and they shared the same mutation c.535C>G(p.Q179E) in IFT74, and c.853G>T(p.E285*) that we found was a new mutation in IFT74 that related with Joubert syndrome. Those findings highlight the need for the inclusion of IFT74 in gene panels for JBST testing.
Highlights
Joubert syndrome (JBTS, OMIM: P213300) is a rare, autosomal recessive ciliopathy characterized by three primary findings: a distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS), hypotonia, and developmental delay (Parisi et al, 2017)
The clinical features and mutations of all these cases were summary in Table 1, Figure 4. This is the second report of IFT74 variants causing a JBTS, validating IFT74 as a JBTS gene
Only one previous report of four cases with JBTS caused by biallelic IFT74 variants has been published by Luo et al (2021) this year
Summary
Joubert syndrome (JBTS, OMIM: P213300) is a rare, autosomal recessive ciliopathy characterized by three primary findings: a distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS), hypotonia, and developmental delay (Parisi et al, 2017). The proband was a 15-month-old female who was referred to our department because of developmental delay She was the first child of non-consanguineous Chinese parents. After birth, craniofacial dysmorphisms with a flat nasal bridge, almond-shaped eye, and a minor midline notch in the upper lips and postaxial polydactyly of the hands and feet were noticed (Figures 1A,B). She achieved rising head and sitting at 3 and 8 months old, respectively. On examination at 15 months of age, she can stand with the assistant and speak several words Her weight was 13 kg, height was 82 cm, body mass index (BMI) was 19.3 kg/m2.
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