Griscelli Syndrome Type 3 in Siblings.

Sir,

Griscelli syndrome (GS) is an autosomal recessive genetic disorder characterized by partial albinism and variable immunological and neurological defects. It was first reported by Griscelli et al. in 1978 in two unrelated patients.[1] It is of three types depending on the gene involved in melanosome transfer.

Two nonidentical siblings (14-year-old boy and 10-year-old girl) were referred from the ophthalmology department for evaluation of silvery gray hair [Figure 1]. The children were born out of nonconsanguineous marriage and had skin hypopigmentation with silvery gray hair over scalp, body, eyebrows, and eyelashes since birth. Similar history of silvery gray hair was present in maternal grandmother. There was no history of fever, irritable behavior, pain abdomen, jaundice, photosensitivity, mental retardation, seizures, headache, bleeding tendency, or recurrent infections. Developmental milestones and anthropometric parameters were normal. Ocular abnormalities such as hypermetropia, strabismus, nystagmus, iris transillumination defects, and bilateral partial foveal hypoplasia were present in both the siblings. The rest of the general and systemic examination was normal.

Figure 1

Nonidentical siblings showing silvery gray hair

Routine investigations such as complete blood count, liver function tests, renal function tests, blood sugar, urine microscopy, and ultrasound abdomen revealed no abnormality. Peripheral blood film showed no inclusions within leukocytes.

Hair microscopy showed large clumps of melanin, irregularly distributed within the medulla region of hair shaft [Figure 2]. The skin biopsy revealed a paucity of melanin pigment in the basal layer [Figure 3]. Electron microscopy and genetic testing were not done due to financial constraints.

Figure 2

Large, irregularly distributed melanin clumps within the medulla of hair shaft

Figure 3

Paucity of melanin pigment in the basal layer (H and E, ×100)

Chediak–Higashi syndrome was excluded due to absence of recurrent infections and inclusions in leukocytes. Absence of neurological problems rules out Elejalde syndrome. Hence, a diagnosis of GS type 3 was made on the basis of presenting features, hair microscopy, and skin biopsy.

The patients are on treatment from an ophthalmologist and regular follow-up. Parents were counseled and reassured about the course and prognosis of the disease.

GS is rare in all the populations, although most of the cases have been reported from Mediterranean and Turkish populations.[2] Very few cases have been reported from India. Up to the best of my knowledge, only two cases of GS Type 3 in nonidentical siblings have been reported in the literature.

Melanosomes are transferred from the center to the tip of melanocyte dendrites through a bidirectional transport. This occurs via microtubules through motor protein kinesin (antegrade) and dynein (retrograde). They are captured in actin filament at the tip by binding to myosin-Va(MyoVa) protein through linker proteins Rab 27aand melanophilin (Mlph). If any member of the tripartite complex (MyoVa, Rab 27a, Mlph) is defective, melanosome transport is impaired resulting in perinuclear accumulation of melanosome.[3] This results in skin hypopigmentation and silvery gray hair.

All the three types present with pigmentary dilution, i.e., silvery gray hair, pale skin with persistent capacity for tanning on sun exposure, and ocular alterations secondary to pigment diminution.[2] Table 1 shows different types of GS with underlying mutations, clinical manifestations, and treatment modalities.

Table 1

Types of Griscelli syndrome, their respective mutations, manifestations and treatment

Type	Mutation	Manifestation	Treatment
GS 1	MyoVa[4]	Severe neurological impairment[5]	Palliative[6]
GS 2	Rab 27a[4]	Recurrent infections; hemophagocytic lymphohistiocytosis in severe cases[7]	Bone marrow transplant[7]
GS 3	Mlph[4]	Skin hypopigmentation and silver gray hair only[4]	Not required[5]

GS – Griscelli syndrome; MyoVa – Myosin-Va; Mlph – Melanophilin

CONCLUSION

GS Type 3 has to be differentiated from GS Type 1, GS Type 2, and Elejalde and Chediak–Higashi syndrome. As treatment, prognosis, and genetic counseling differ to a great extent among various types, accurate genetic diagnosis early in life certainly plays a significant role.[7]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients' parents have given their consent for patients' images and other clinical information to be reported in the journal. The patients' parents understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.