Table 1 Differential diagnosis inherited hypopigmentation disorders associated with neurological manifestations
Syndrome | Gene defect | Skin features | Neurological features | Other associated features | Investigations |
|---|---|---|---|---|---|
Chediak-Higashi syndrome (CHS) | AR LYST gene defect (1q42-43) | Partial albinism, with a peculiar silvery gray scalp hair, eyebrows, and eyelashes | Present either: 1) Primary, e.g., developmental abnormalities as learning disabilities 2) Secondary to the accelerated phase of CNS-HLH or CNS infections | 1) Immunodeficiency with repeated and persistent infections 2) Hyperinflammation with secondary HLH | Peripheral blood/bone marrow smear reveals giant azurophilic granules within neutrophils/leukocyte precursor cells. Hair Trichogram reveals small clumped melanin granules, regularly arranged. |
Oculocerebral hypopigmentation syndrome, OHS (cross-type) | AR Unknown gene defect (3q27.1q29) | Generalized hypopigmentation with photosensitivity Silvery scalp hair, eyebrows, and eyelashes | Psychomotor delay with athetoid movements, ataxia, spasticity, joint contractures, and intellectual disability | Ophthalmological manifestations: microphthalmia and microcornea Growth retardation Distinctive facies: dolichocephaly, a highly arched palate, widely spaced teeth High-pitched cry Oligophrenia | Â |
Griscelli syndrome | AR | Partial albinism with silvery gray scalp hair, eyebrows, and eyelashes | Â | Â | Trichogram reveals large melanin clumps unevenly distributed. |
GS1/Elejalde syndrome | MYO5A (15q21.) | Â | GS1: hypotonia, encephalopathy, seizures, and psychomotor delay | GS1: no immne dysfunction | |
GS2 | RAB2A (15q21.) | Â | GS2: neurologic manifestations in association with the accelerated phase CNS-HLH | GS2: immune dysfunction is evident. | |
Prader-Willi syndrome | Defective region of chromosome 15 ( 15q11.2-q13) | Hypopigmentation of the hair, eyes, and skin | Hypotonia, cognitive impairment, and developmental delay | Distinctive facies: dolicoceohaly with almond-shaped eyes, a thin upper lip, a downturned mouth, hyperphagia with morbid obesity, and hypogonadism with delayed puberty | Â |
Angelman syndrome | Defective region of chromosome 15 involving the UBE3A gene | Fair skin and hair | Intellectual disability and seizures Behavioral features: happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements | Microcephaly and scoliosis | Â |
Phenylketonuria | AR PAH gene defect (12q23.2) | Fair skin and hair, eczema photosensitivity, keratosis pilaris, and scleroderma-like plaques | Progressive developmental delay and intellectual disability Epilepsy Extrapyramidal manifestation | Musty or mousy odor | The upper reference limit for Phe in whole blood or plasma in neonates is < 150 μmol/L and slightly lower (< 120 μmol/L) in older children. |
Menkes syndrome | XLR Defective ATP7A gene (Xq13.3) | Abnormal kinky hair (short, sparse, coarse, twisted often hypo or depigmented) especially in the areas of friction | Resistant seizures, developmental regression spasticity, and weakness of the extremities | Skeletal changes, including pectus excavatum and spontaneous fractures due to generalized osteoporosis. The joints are hyperextensive, and loose. | Trichogram can reveal pili torti. |
Hypomelanosis of Ito | Postzygotic mutations in a variety of pigmentation-associated genes | Unilateral or bilateral cutaneous macular hypopigmented whorls, streaks, and patches along the lines of Blaschko | Seizures, mental retardation, developmental delay, cerebral malformations, hypotonia, deafness, and visual problems | Glomerulocystic kidney disease Skeletal abnormalities Dental abnormalities | Â |