Griscelli Syndrome Clinical Presentation

Updated: Jul 26, 2019
  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
  • Print
Presentation

History

Often, the first manifestation of Griscelli syndrome that is noted is silver hair. The differential diagnosis of the disease in a patient presenting with silvery hair includes primarily Griscelli syndrome, Chediak-Higashi syndrome, and Elejalde syndrome. Not long after, the immunologic effects of Griscelli syndrome caused by mutations in RAB27A are noted. The immunologic defects of Griscelli syndrome resemble those of HLH syndrome and the X-linked lymphoproliferative syndrome. Although Hermansky-Pudlak disease is a form of albinism, it does not present with silver hair or immunologic findings like Griscelli syndrome. [32, 33]

Some patients can remain in good health, with only limited syndomes into their 20s. [34]

The neurologic effects of Griscelli syndrome caused by defects in MYO5A usually manifest early in life and even close to birth.

Severe neurologic manifestations in Griscelli syndrome are associated with defects in the MYO5A gene. Severe neurologic symptoms are noticeable at birth without any sign of an accelerated phase. CNS disorder is stable and never regresses with time. The symptoms consist of the following:

  • Obstructive hydrocephalus without hematological abnormalities or organomegaly [35]

  • Bilateral basal ganglia involvement [36]

  • Hypotonia

  • Absence of coordinated voluntary movements

  • Bulbar poliomyelitis

  • Encephalopathy

  • Hemiparesis

  • Peripheral facial palsy

  • Spasticity

  • Seizures

  • Psychomotor retardation

  • Severe retarded psychomotor development similar to that observed in Elejalde syndrome

Griscelli syndrome caused by the RAB27A mutation can also cause neurologic manifestations in association with HS (accelerated phase). Neurologic problems may be the first sign of HS (accelerated phase). Neurologic manifestations occurring in patients with Griscelli syndrome caused by the RAB27A mutation are related to lymphocyte infiltration of the CNS. These problems are not as severe as those found in Griscelli syndrome caused by MYO5A mutations.

The symptoms include hyperreflexia, seizures, signs of intracranial hypertension (eg, vomiting, altered consciousness), regression of developmental milestones, hypertonia, nystagmus, and ataxia. Psychomotor development is normal at onset, and regression of CNS signs, at least in part, can be observed during remission, although some sequelae may be irreversible.

At birth, nonspecific findings can occur that include petechiae and hepatosplenomegaly.

A history of severe infections associated with the occurrence of acute phases of uncontrolled lymphocyte and macrophage activation, so-called HS (accelerated phase), can be present in patients with mutations in RAB27A. These infections are not present in patients with mutations in MYO5A.

In 2003, Dinakar et al [37] reported on a 6-year-old girl with Griscelli syndrome. The patient experienced perpetual infections, seizures, regression of milestones, silvery hair, and organomegaly. Her brain was affected with unusual features of a Dandy-Walker cyst, and her blood and bone marrow were also affected, manifesting hypergammaglobulinemia.

Al-Idrissi et al reported on a preterm neonate with Griscelli syndrome type 3 who presented with silvery-gray hair and eyelashes, respiratory distress, and intracerebral hemorrhage. The authors stressed the importance of early differentiation of type 3 from Griscelli syndrome type 2, which is associated with a curable (but life threatening) immune disorder. [38]

Next:

Physical Examination

Mutations in both MYO5A and RAB27A cause pigmentary dilution and other internal organ abnormalities.

Skin manifestations of both Griscelli syndrome variants include granulomatous skin lesions, partial albinism, and generalized lymphadenopathy. The appearance of the hair has been variably described as silvery gray, silvery, grayish golden, or dusty. The skin is usually pale, but the albinism is not complete. Kharkar et al [39] described a phenotype of Griscelli syndrome with circumscribed pigment loss.

Liver manifestations include hepatosplenomegaly and jaundice as a result of hepatitis.

Patients can present with pallor as a result pancytopenia.

Neurologic impairments can occur as a result of CNS lymphohistiocytic infiltration with erythrophagocytosis. Upon physical examination, especially in children with mutations in MYO5A, hemiparesis, peripheral facial palsy, spasticity, seizures, psychomotor retardation, and severe retarded psychomotor development may be noted.

Ocular defects can occur in Griscelli syndrome. Partial ocular albinism has been observed in some patients with Griscelli syndrome, but retinal degeneration has not been reported in this disorder. [40]

Akcakus et al [41] noted Griscelli syndrome in an infant associated with asymmetric crying facies.

Rajadhyax et al [35] noted obstructive hydrocephalus without hematological abnormalities or organomegaly in a patients with Griscelli syndrome.

Previous
Next:

Complications

Patients with Griscelli syndrome can have HS; infections; and neurologic, immunologic, and bleeding problems. Köse et al [42] noted the development of in situ melanoma after allogeneic bone marrow transplantation in a person with Griscelli syndrome type 2.

Previous