An Unusual Case of Peters Plus Syndrome with Sexual Ambiguity and Absence of Mutations in the B3GALTL Gene
The patient presented here is a 4 year-old girl of healthy consanguineous parents. Her younger sister was also healthy. Prenatal echography revealed short limbs. The PPS was evoked at birth and the patient was addressed for facial dimorphisms. Clinical investigations including karyotype, pediatric and ophthalmologic exams were performed after informed consent. At birth, she was underweight 2660 g (-1.6 SD), her length was 46 cm (-1.4 SD), and occipitofrontal circumference (OFC) 34 cm (±0 SD). Apgar score was 8/10. Neonatal exams revealed complete bilateral cleft lip and palate, large anterior fontanel, hypertelorism and a coccygeal dimple suggesting vertebral schisis. She also had disproportionate short stature and facial dysmorphism including dolichocephaly, round face, small nose with reverted nostrils and erased and long philtrum. Short limbs in the proximal segment and brachydactyly with bilateral clinodactyly of the fifth finger were also seen. Transfontanel ultrasound imaging showed quadri ventricular hydrocephaly and microcephaly caused by agenesis and atrophy of corpus callosum. Ophthalmologic exam revealed bilateral central corneal opacity without buphthalmos or congenital glaucoma.\nIn addition to these typical features for PPS, the patient showed sexual ambiguity without urogenital anomalies. In fact, she had hyper pigmented labia majora with pseudo scrotal aspect without clitoris hypertrophy, but she had two distinct (urethral and vaginal) orifices. Abdomen ultrasound showed a morphologically normal uterus with normal size, but renal pyelo-calicial dilation on left side was appreciated. Chromosome analysis on lymphocytes revealed a normal 46, XX karyotype. At the age of 4 years, the patient's weight was 11 kg (-2SD), length 78 cm (-3SD) and OFC 47 cm; without delayed psychomotor development.\nB3GALTL is the only gene known to be associated with Peters Plus syndrome, and most affected individuals tested to date are homozygous for a hot spot splice mutation in the acceptor splice site of intron 8 (c.660 + 1G > A). Sequencing of the 15 coding exons and flanking introns boundaries of the B3GALTL gene showed that the patient is B3GALTL mutation-negative. But we cannot exclude the presence of splice site mutation distant from the coding sequence, or mutation in the regulatory sequences of the gene. In addition, screening of the three intragenic SNP(s) which are described to be associated with B3GALTL gene mutations showed that the patient is heterozygous for two SNP (rs9315120, rs877103) and homozygous for the rs877104 one (). These results suggest but not confirm the exclusion of the B3GALTL gene in this case ().