Congenital Hypopigmentary Disorders with Multiorgan Impairment: A Case Report and an Overview on Gray Hair Syndromes

Abstract

The term congenital hypopigmentary disorders refers to a wide group of heterogeneous hereditary diseases, clinically characterized by inborn pigmentary defects of the iris, hair, and/or skin. They include Gray Hair Syndromes (GHSs), a rare group of autosomal recessive genodermatosis hallmarked by inborn silvery gray hair. GHSs encompass Griscelli, Chediak⁻Higashi, Elejalde, and Cross syndromes, which are all characterized by a broad spectrum of severe multisystem disorders, including neurological, ocular, skeletal, and immune system impairment. In this manuscript, we describe in detail the clinical, trichoscopic, and genetic features of a rare case of Griscelli syndrome; moreover, we provide an overview of all the GHSs known to date. Our report highlights how an accurate clinical examination with noninvasive methods, like trichoscopy, may play a crucial rule in diagnosis of rare and potentially lethal genetic syndromes such as Griscelli syndrome, in which timely diagnosis and therapy may modify the clinical course, quality of life, and likelihood of survival.

Keywords: congenital hypopigmentary disorders; genetic skin disorders; genodermatoses; gray hair syndromes; griscelli syndrome; pigmentation disorders.

Figure 1

Clinical findings of our patient. (A) A 2-year-old Caucasian child with congenital silvery gray scalp hair, eyebrows, and eyelashes and fair skin. He had also brown irises and very fair skin with mild tanning capacities after sun exposure; (B) Diffuse silvery hypertrichosis: unmedullated, short, and soft hypopigmented hairs on the back of the patient.

Figure 2

Light microscopic examination of hair shafts of the proband (A,B) and of a healthy control (C,D). Giant uneven melanin granules in the medullar zone of the hair’s proband at light microscopy (A) 40× magnification; (B) 100× magnification. Aspect on light microscopy of a black hair of a healthy Caucasian control. The pigment is homogeneous and evenly distributed in the hair shaft. (C) 40× magnification; (D) 100× magnification.

Figure 3

Electropherograms of a control and the affected subject showing the homozygous variant c.467 + 1G > C. Genomic DNA was extracted from bone marrow cells of the proband using an automated nucleic acid purification platform (Maxwell® 16, Promega). The five coding exons of RAB27A gene and their flanking intronic regions were amplified by PCR with specific primers (available upon request) and then sequenced by Sanger Sequencing (ABI 3130 Genetic Analyser, Applied Biosistems). The cDNA analysis from total RNA isolated from pretransplantation bone marrow of the proband or from the parents’ peripheral blood sample could define the effect of germline mutations of RAB27A gene on its transcription.