A case with central and peripheral hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome) plus cataract

Endocrine Aspects of 4H Leukodystrophy: A Case Report and Review of the Literature

“…The majority of patients also exhibit pronounced myopia [7]. The dental abnormalities seen in 4H leukodystrophy may be overt, with several teeth failing to develop, or they may be very subtle, requiring X-rays for identification [10, 11, 21]. This patient had congenital absence of both mandibular second bicuspids but had also been found to have two supernumerary teeth underneath her secondary mandibular incisors; it is uncertain whether these truly represent supernumerary teeth or whether they are ectopic, malformed bicuspids.…”

“…Cerebellar dysfunction is the most frequent neurological abnormality [7, 10–13, 21], and the majority of patients also have cognitive dysfunction [1, 6, 7, 9, 12, 18, 22]. Progressive neurological deterioration is a characteristic feature of patients with 4H leukodystrophy and other Pol III-related leukodystrophies, with many patients becoming wheelchair-bound and exhibiting significant cognitive impairment by the time they reach young adulthood [1, 7, 10, 13, 18, 21, 23].…”

“…Progressive neurological deterioration is a characteristic feature of patients with 4H leukodystrophy and other Pol III-related leukodystrophies, with many patients becoming wheelchair-bound and exhibiting significant cognitive impairment by the time they reach young adulthood [1, 7, 10, 13, 18, 21, 23]. However, the age-of-onset of this neurological dysfunction is variable.…”

“…The majority of females with 4H leukodystrophy lack spontaneous pubertal development, suggesting that hypogonadotropic hypogonadism is usually established prior to adolescence in this disorder [12, 13]. Although hypogonadism has not been recognized until early adulthood in some male patients, normal initial pubertal development followed by progressive hypogonadism has not been described [9, 10]. Some patients also have growth hormone deficiency, which was shown to be progressive in one individual [9, 12].…”

Advances In the Diagnosis of Leukodystrophies

“…Krabbe, Aicardi-Goutières [3,33] Neuropsychiatric symptoms Metachromatic, adrenoleukodystrophy, adultonset autosomal dominant leukodystrophy, hereditary diffuse leukoencephalopathy with spheroids and cerebrotendinous xanthomatosis 18q deletion [4,5,7,41,61,66] Macrocrania Alexander, Canavan and megalencephalic leukoencephalopathy with subcortical cysts [30,63,64] Relative macrocrania Krabbe and metachromatic [3,4] [54,80] Tooth enamel hypoplasia Oculodentodigital dysplasia [67] Ophthalmological Cataracts Cerebrotendinous xanthomathosis Hypomyelination with congenital cataracts; 18q deletion; Cockayne; and Pol III-related (one case) [8,61,73,81] Microphthalmia Oculodentodigital dysplasia and Cockayne [67,73] Nystagmus Pelizaeus-Merzbacher (except PLP1 null syndrome), Pelizaeus-Merzbacher-like disease and Pol III-related (gaze-evoked) [6,44,45,54,55] Progressive external ophthalmoplegia, ptosis MRI pattern recognition is also useful for discriminating between the many hypomyelinating disorders [16]. Beyond the common diffuse hypomyelination [16], each of these disorders have other specific characterizing features on MRI, which can help to differentiate one from the others [16].…”