LAUSR

A 16-year-old boy was admitted to our clinic with facial dysmorphism involving microphthalmia, short narrow palpebral fissures, a narrow nose, a depressed nasal bridge, micrognathia, and clinodactyly. Neurological examination revealed spastic tetraparesis, upper and lower limb hyperreflexia, and bilateral Babinski sign. He was born to consanguineous parents. He had neurodevelopmental delay and previous surgery for bilateral cataracts. The patient’s parents had no similar symptoms. Results were normal for complete blood count, routine biochemistry, plasma lactate, tandem mass spectrometry, blood and urine quantitative amino acids, urine organic acids, very long chain fatty acids, and parathyroid hormone levels. Brain magnetic resonance imaging (MRI) showed hypomyelination and bilateral abnormal signal changes in the basal ganglia (caudate nucleus, putamen, and globus pallidus), thalamus, dentate nucleus and periventricular and deep white matter on T1, T2-weighted, and FLAIR sequence images (Fig. 1a–f). Bilateral calcification of the basal ganglia, thalamus and deep white matter was observed on computed tomography (CT) of cranium scans (Fig. 2a, b). GJA1 gene mutation analysis was performed with Sanger sequencing and revealed a previously unreported homozygous c.168_169insT (p.Gln57SerfsTer6) variant. This was a frameshift variant and interpreted as “pathogenic” according to the “Standards and guidelines for the interpretation of sequence variants” released by the American College of Medical Genetics and Genomics (ACMG). Oculodentodigital dysplasia (ODDD) is a rare and hypomyelinating disorder caused by mutations in the GJA1 gene which encodes the gap junction protein connexin43 (Cx43) [1, 2]. Most ODDD patients maintain a highly penetrant autosomal dominant mode of transmission, but some cases of apparent autosomal recessive (AR) inheritance have been reported, as in our patient. ODDD contains a variety of anomalies which can be ocular (microcornea, short palpebral fissures, epicanthal folds, cataracts, glaucoma), craniofacial (microcephaly, narrow nasal bridge, hypoplastic alae nasi, prominent columella, anteverted nares, cleft lip/palate), dental (enamel hypoplasia, partial anodontia, microdontia, premature loss of teeth), or skeletal (syndactyly of fourth and fifth fingers, camptodactyly and midphalangeal hypoplasia of the fifth finger, skull and vertebral hyperostosis, hip dislocation) [3]. Neurologic features are frequent and include dysarthria, neurogenic bladder disturbances, spastic paraparesis/tetraparesis, ataxia, anterior tibial muscle weakness, seizures, and mental retardation [4]. The main MRI abnormality in ODDD is hypomyelination, but there are others such as hypointensity of the deep gray matter, which may reflect iron deposition, and * Nihal Olgac Dundar [email protected]