Griscelli syndromeE70.3

Rare, autosomal recessive disorder with diffuse hypopigmentation of skin and hair. The syndrome occurs in 3 different variants (GS type 1 to 3).

• Gricelli syndrome type 1 occurs without immunological defects.
• In Gricelli syndrome type 2, immunological disorders occur. Large pigment aggregates located in the hair shaft are histologically detectable. Furthermore, the number of mature melanosomes is increased in melanocytes.
• Gricelli syndrome type 3 is characterized only by hypomelanosis with silver-colored hair and pale skin (Nouriel A et al. 2015).

The syndrome is genetically heterogeneous.

Causes include mutations in the MYO5A gene, which codes for myosin VA (GS1), or in the RAB27A gene (GS2). The RAB27A and MYO5A genes are located in the chromosome region 15q21. Patients with RAB27A mutations manifest cytotoxic defects and uncontrolled activation of T lymphocytes and macrophages in addition to the pigment abnormality. The result is a so-called hemophagocytic lymphohistiocytosis. Patients with a defect in myosin VA have an early onset of neurological symptoms in addition to the pigment disorder, without immune system disorders.

GS3 (OMIM 609227) is caused by a mutation in the MLPH gene, which codes for the melaophilin protein.

Melanosomes are transported by a bidirectional transport from the center to the tip of the melanocyte thirds. This occurs via microtubules through the motor proteins kinesin (antegrade) and dynein (retrograde). They are retained in the actin filament at the tip by binding to the myosin-Va (MyoVa) protein via the linker proteins Rab 27a (see RAB27A gene below) and melanophilin (Mlph). If one of the members of the three-part motor complex(MyoVa, Rab 27a, Mlph) is defective, melanosome transport is impaired, which leads to a perinuclear accumulation of melanosomes. This manifests itself in hypopigmentation of the skin and silvery-gray hair. In all three variants of Griscinelli syndrome, there is diffuse hypopigmentation of the skin, silvery-grey hair, pale skin but with a persistent tendency to tan when exposed to sunlight - furthermore, eye changes as a result of the pigment reduction.

Diffuse hypopigmentation of skin and hair, depending on the type, possibly associated with neurological disorders and immune defects. Untreated, the disease is fatal. Febrile attacks with hepatomegaly, lymphadenopathy, suppression of hematopoiesis cells and neurological disorders are characteristic. In contrast to the other syndromal albinism forms, patients with GS do not develop eye involvement (see oculocutaneous albinism below).

Chédiak Higashi Syndrome

Hermansky-Pudlak syndrome

Waardenburg Syndrome

Oculocutaneous albinism

Two siblings (a 14-year-old boy and a 10-year-old girl) were referred from the ophthalmology department for evaluation of silver-gray hair. The children were from a non consanguineous marriage and had hypopigmentation of the skin with silvery gray hair on the scalp, body, eyebrows and eyelashes since birth. The maternal grandmother had a similar history of silver-gray hair. There was no history of fever, irritable behavior, abdominal pain, jaundice, photosensitivity, mental retardation, seizures, headaches, bleeding tendency, or recurrent infections. Ocular abnormalities such as hypermetropia, strabismus, nystagmus, iris transillumination defects and bilateral partial foveal hypoplasia were present in both siblings. The rest of the general and systemic examination was normal (Gupta I et al. 2022)

1. Griscelli C, Durandy A, Guy-Grand D, Daguillard F, Herzog C, Prunieras M (1978) A syndrome associating partial albinism and immunodeficiency. Am J Med. 65: 691-702
2. Griscelli C, Prunieras M (1978) Pigment dilution and immunodeficiency: a new syndrome. Int J Dermatol 17): 788-791
3. Gupta I et al (2022) Griscelli Syndrome Type 3 in Siblings. Int J Trichology. 14:38-40.
4. Habermehl S et al. (2003) Griscelli syndrome: A case report. Clinical Pediatrics 215: 82-85
5. Nouriel A et al.(2015) Griscelli Syndrome Type 3: Two New Cases and Review of the Literature.
6. Pediatr Dermatol 32:e245-248.