BH15 Nonsyndromic hypotrichosis: a rare case of congenital hypotrichosis 15 and management with minoxidil

Abstract We present a rare gene abnormality causing nonsyndromic congenital hypotrichosis. Only nine individuals with this condition have been described since it was first reported in 2020. Our case demonstrates some response to topical minoxidil, supporting the postulated mechanism of action of this drug in these patients and use in congenital hypotrichosis. A 2-year-old girl presented with sparse, wiry, hair that had failed to grow since the age of 3 months. On examination she had short and very curly hair on the scalp and occasional downy hairs on the body. Her eyebrows, eyelashes, skin, nails and teeth were normal. She was the first child of consanguineous ethnically Iranian parents, without any family history of the disease. Subsequently, her parents had a male child who was unaffected. She was healthy and had no developmental issues. Microscopy of the hair supported congenital hypotrichosis. Typical features include miniaturization of the hair follicle, irregularities of the cuticle and an underdeveloped medulla. DNA exome sequencing of a virtual panel of genes associated with ectodermal dysplasias revealed homozygosity for a pathogenic mutation in the C3orf52 gene: c.438_442del, p.(Thr148SerfsTer2), a small intragenic frameshift deletion of five nucleotides. The diagnosis was congenital hypotrichosis 15. Application of minoxidil 2% topical application led to some improvement in hair length. This was changed to minoxidil 5%, with the option to add in oral minoxidil 0.625 mg. Congenital hypotrichosis 15 is a type of localized autosomal recessive hypotrichosis, mediated by reduced 2-acyl-lysophosphatidic acid biosynthesis, resulting in downregulation of hair growth and differentiation pathways. The condition is not associated with any other systemic involvement, and interestingly the eyebrows may be spared, as with our patient. Effective treatments have not yet been established, but topical minoxidil shows emerging evidence in the literature. The improvement is explained by the effect of minoxidil on cell growth, anagen duration and follicular size. Our case also confirms that the changes in the C3orf52 gene leading to congenital hypotrichosis are caused by null alleles (no expected protein expression). In all reported cases, the C3orf52 gene abnormality was present in the homozygous state, corresponding with the extreme rarity of this condition.