Trichothiodystrophy (TTD; sulfur-deficient brittle hair syndrome) is a rare autosomal recessive disorder, which manifests with brittle hair, mental retardation, ichthyosis and decreased fertility. Mutations in the C7orf11 gene have been associated with nonphotosensitive trichothiodystrophy.
A 19 years old male patient, born to consanguineous parents of Arab-Muslim descent, was referred for dialysis treatment due to severe renal failure. Upon admission, additional unique features were noted, including developmental delay, mental retardation, splenomegaly, pancytopenia, hypogonadism and brittle hair. Microscopic examination of the patient`s hair revealed trichorrhexis nodosa. Abdominal ultrasound demonstrated splenomegaly and small echogenic kidneys. Head CT and ophthalmological evaluation were considered normal. The patient required several dialysis treatments following which clinical improvement was seen.
The patient is the 4/8 siblings, one of whom (17 years old sister) showed similar multisystem involvement, including developmental delay and brittle hair, however without renal compromise. Family history was further notable for 14 additional affected individuals, ages 2-36 years, two of whom are married without offspring.
Under clinical suspicion of nonphotosensitive-TTD, sequencing of the coding exons of C7orf11 was initially performed in the index patient and his mother, and had revealed the patient to be homozygous for a novel c.504dupA mutation, and his mother a heterozygote carrier. Further molecular diagnosis of the affected family members is underway.
To conclude, we describe a multiplex kindred with 16 individuals exhibiting features of nonphotosensitive trichothiodystropy, including mental retardation, brittle hair and male infertility. Molecular diagnosis in this highly affected family may enable genetic counseling and prenatal diagnosis for future pregnancies.
