Akademik Veri Yönetim Sistemi
EuroDysmorpho 2022, Barcelona, İspanya, 14 - 17 Eylül 2022, ss.95-96
Nance-Horan syndrome (OMIM #302350) is an ultra rare, X-linked disorder that is
characterized by congenital cataracts, dental anomalies, dysmorphic features and
intellectual disability. There have been around 30 families reported in the literature so far
and the underlying gene has been identified as NHS. Here we report two siblings; a 15-yearold female and 20-year-old male, both were severely affected with classical findings of this
rare phenotype.
15-year-old female patient was referred to our outpatients clinics for syndromic evaluation.
She was born by normal spontaneous vaginal birth at 38th week of gestation with a birth
weight around 2000 gr (<3p). She was diagnosed with bilateral congenital cataracts and had
an operation at 2nd month of age and then 6 years of age. Her neuromotor development
was delayed comparing to her peers. She was diagnosed with learning disability at 8 years of
age and she started to have special education. Around age of 13, bilateral flexion
contractures of knees were developed and she started to have difficulty in climbing stairs.
Her cranial MRI showed hypoplastic midbrain and vermis hypoplasia. Parents of the proband
were not related and it was learned that she had an older male sibling with similar symptoms. In her physical examination; weight was 40 kg (-2,82SD), height was 165 cm
(+0,52SD), head circumference was 55 cm ( -0,46SD) and body-mass-index (BMI) was -4,04.
She had long narrow face with high forehead, broad eyebrows, bilateral ptosis, prominent
nasal bridge, multiple dental caries and abscent right lateral incisor, long slender extremities
and arachnodactyly of the fingers and toes. Brother of the proband was born at 40th week
of gestation with birthweight of 4000 gr. He had respiratory distress due to meconium
aspiration and he has spent two hours in neonatal intensive care unit (NICU). His
neuromotor developmental skills were delayed and he was diagnosed with bilateral
cataracts around the age 3 and had operation. He had special education for learning
disability. In his physical examination; weight was 60 kg (-0,5SD), height was 175 cm
(+0,38SD), head circumference was 56 cm ( -0,03SD) and body-mass-index (BMI) was -
0,79. He also had long narrow face, broad eyebrows, long nose with prominent bridge and
long slender extremities. Whole exome sequencing was performed at the proband and a
novel heterozygous c.1241-4delC variant at NHS gene was detected. Sanger sequencing of
the relevant variant at the affected brother revealed the variant as hemizygous state. In
addition to that, segregation analysis was done by sanger sequencing at the unaffected
mother and the variant was detected at her in heterozygous state similar to proband. Since
the proband was female who were affected severely, further karyotype analysis and
microarray analysis (Agilent, SNP array+Array CGH, 180K) for X chromosomal aberrations
were done and revealed normal results. It was further planned to perform X-linked
inactivation assay from the peripheral blood of the proband to identify possible skewed X
inactivation. It is known that female patients are affected from the milder form of the
syndrome and mostly opthalmological findings are seen. To our knowledge this is the first
female patient in the literature with full clinical manifestation of this rare phenotype.