Griscelli Syndrome: Insights into a Rare Inherited Condition: A Case Report

INTRODUCTION

Griscelli syndrome (GS) is a rare autosomal recessive genetic disorder characterised by skin and hair pigment dilution, immune system dysfunction and, in some subtypes, severe neurological involvement. The condition was initially reported in 1978 by Griscelli and Siccardi in Paris.^[1] So far, only about 150 cases of GS have been documented worldwide, underscoring its extreme rarity. Most of these cases have been described from Mediterranean regions, particularly Turkey.^[2] Up until now, roughly 20 cases of GS type 1 (GS1) have been documented, which also include individuals diagnosed with Elejalde syndrome (ES).^[3] ES presents with silvery-grey hair, neurological impairment, inclusion bodies within fibroblasts, eye abnormalities and a suntanned appearance of the skin.^[4] Up to now, no instances of GS1 or GS type 3 (GS3) have been documented from India.^[5] Despite an extensive literature review, not a single case of GS1 has been reported from India.

CASE REPORT

A 9-month-old female was brought to the hospital by her mother with complaints of fever and seizures. She was born through caesarean section due to maternal pregnancy-induced hypertension. She was a full-term infant weighing 2.4 kg, who cried right after birth. Her immunisation record was complete. The mother reported that the child’s head flopped back when lifted or while attempting to hold it. The mother had previously suffered a spontaneous miscarriage at 3 months of gestation. There was no family history of a similar disorder. The child, born to parents in a third-degree consanguineous marriage, was their only offspring. She had no history of recurrent infections. During the physical examination, her hair appeared lighter than that of her family with silvery-grey scalp hairs, eyebrows, eyelashes and body hairs [Figures 1 and 2]. The child had yet to attain neck control or a social smile and shows signs of hypotonia, indicating delayed psychomotor development. Abdominal examination revealed no organ enlargement, and ophthalmic evaluation was normal.

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Figure 1:

Silvery-grey scalp hairs, eyebrows, eyelashes, and body hairs.

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Figure 2:

Silver-grey eyelashes.

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The initial laboratory investigations showed anaemia [haemoglobin: 10.6 g/dL, haematocrit: 36.1%, white blood cell: 15770 cumm, peripheral blood smear and lumbar puncture were within normal limits, blood culture showed no organism. Microscopic examination of the hair shaft showed an abnormal pattern, with large pigment clumps observed [Figures 3 and 4]. Whole exome sequencing showed a homozygous nonsense variant in exon 5 of the MYO5A gene.

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Figure 3:

Microscopic view of the patient’s hair shaft (red arrow) (10×).

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Figure 4:

Larger microscopic view of the patient’s hair shaft (red arrow) (40×).

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A diagnosis of GS1 is confirmed by the combination of silvery-grey hair, psychomotor delay, hypotonia, irregular pigment clumps in the hair shaft and a genetic defect detected through whole exome sequencing.

The patient was managed with antiepileptic medications for seizure control, along with supportive physical therapy to improve hypotonia and aid developmental progress.

DISCUSSION

GS is classified into three types, each defined by distinct genetic defects and their associated clinical features.^[6] GS1 is characterised by severe neurological impairment in the absence of immune dysfunction. It results from mutations in the MYO5A gene, which encodes a motor protein crucial for the movement of melanosomes and neurosecretory vesicles. GS type 2 is marked by immune system abnormalities and haemophagocytic activity, caused by mutations in RAB27A, a protein that governs membrane trafficking, including the transport of melanosomes and various regulated secretory processes. GS type 3 primarily affects skin and hair pigmentation and results from mutations in the melanophilin gene.^[7] Clinically, GS1 must be differentiated from ES and Chediak–Higashi syndrome (CHS). ES is characterised by silvery hair, sun-induced bronze skin pigmentation, early neurological deficits and the absence of immune dysfunction. Hair shafts exhibit uneven melanin clumping, and fibroblasts may contain abnormal inclusion bodies.^[8] CHS is characterised by partial oculocutaneous albinism, compromised immunity, a mild tendency to bleed and neurological manifestations that appear later in life. It may progress to haemophagocytic lympho-histiocytosis, the main cause of death. Enlarged granules in leucocytes on a peripheral smear are a hallmark finding.^[9] A detailed comparison of these syndromes is listed in Table 1.

CONCLUSION

GS1 should be suspected in infants with silvery-grey hair, psychomotor regression and seizures. Examination of the hair shaft can help distinguish GS1 from other disorders causing hypopigmentation. Early detection of GS1 is crucial, as the condition is progressive and leads to severe neurological disability if left unrecognised. Although no cure exists, early supportive care, including antiepileptic medications and physiotherapy, can help improve the patient’s quality of life. Genetic counselling plays an important role, especially in families with consanguineous marriages, to guide reproductive choices and evaluate the likelihood of recurrence in future offspring.