Griscelli Syndrome Clinical Presentation

  • Author: Noah S Scheinfeld, MD, JD, FAAD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jul 18, 2011
 

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.[20, 21]

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[22]
  • Bilateral basal ganglia involvement[23]
  • 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[24] 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.[25]

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Physical

Mutations in both MYO5A and RAB27A cause pigmentary dilution and other internal organ abnormalities. Note the following physical findings:

  • 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[26] 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.[27]
  • Akcakus et al[28] noted Griscelli syndrome in an infant associated with asymmetric crying facies.
  • Rajadhyax et al[22] noted obstructive hydrocephalus without hematological abnormalities or organomegaly in a patients with Griscelli syndrome.
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Causes

Griscelli syndrome is a genetic disorder related to mutations in MYO5A and RAB27A (see Pathophysiology).

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Coauthor(s)

Ann M Johnson, MD  Assistant Professor of Clinical Radiology, University of Pennsylvania School of Medicine; Director, Body MRI, Department of Radiology, Children's Hospital of Philadelphia

Ann M Johnson, MD is a member of the following medical societies: American Roentgen Ray Society, International Society for Magnetic Resonance in Medicine, Radiological Society of North America, Society for Pediatric Radiology, and Society of Computed Body Tomography and Magnetic Resonance

Disclosure: Nothing to disclose.

Specialty Editor Board

Julie C Harper, MD  Assistant Program Director, Assistant Professor, Department of Dermatology, University of Alabama at Birmingham

Julie C Harper, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Stiefel Honoraria Speaking and teaching; Allergan Honoraria Speaking and teaching; Intendis Honoraria Speaking and teaching; Coria Honoraria Speaking and teaching; Sanofi-Aventis Honoraria Speaking and teaching

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD  Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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