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Ermine phenotype

General Information (adopted from Orphanet):

Synonyms, Signs:	PIGMENTARY DISORDER WITH HEARING LOSS BLACK LOCKS WITH ALBINISM AND DEAFNESS SYNDROME, INCLUDED BADS, INCLUDED O&#39 Doherty syndrome Pigmentary disorder with hearing loss
Number of Symptoms	26
OrphanetNr:	999
OMIM Id:	227010
ICD-10:	E70.3
UMLs:	C1856899
MeSH:	C535508
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	3 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Syndromic genetic deafness
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare otorhinolaryngologic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000252)	Microcephaly	Occasional [Orphanet]	832 / 7739
2	(HPO:0002226)	White eyebrow		10 / 7739
3	(HPO:0000445)	Wide nose	Occasional [Orphanet]	190 / 7739
4	(HPO:0002227)	White eyelashes		11 / 7739
5	(HPO:0000639)	Nystagmus	Occasional [Orphanet]	555 / 7739
6	(HPO:0000483)	Astigmatism	Occasional [Orphanet]	67 / 7739
7	(HPO:0001107)	Ocular albinism	Occasional [Orphanet]	40 / 7739
8	(HPO:0000613)	Photophobia	Occasional [Orphanet]	158 / 7739
9	(HPO:0008527)	Congenital sensorineural hearing impairment		165 / 7739
10	(HPO:0008625)	Severe sensorineural hearing impairment		150 / 7739
11	(HPO:0000407)	Sensorineural hearing impairment	Very frequent [Orphanet]	524 / 7739
12	(HPO:0001256)	Intellectual disability, mild		141 / 7739
13	(HPO:0004209)	Clinodactyly of the 5th finger	Occasional [Orphanet]	288 / 7739
14	(HPO:0001770)	Toe syndactyly	Occasional [Orphanet]	149 / 7739
15	(HPO:0004322)	Short stature	Frequent [Orphanet]	1232 / 7739
16	(HPO:0001022)	Albinism	Very frequent [Orphanet]	43 / 7739
17	(HPO:0005585)	Spotty hyperpigmentation		8 / 7739
18	(HPO:0007400)	Irregular hyperpigmentation	Frequent [Orphanet]	72 / 7739
19	(HPO:0001045)	Vitiligo		13 / 7739
20	(HPO:0001053)	Hypopigmented skin patches	Very frequent [Orphanet]	80 / 7739
21	(HPO:0001252)	Muscular hypotonia	Occasional [Orphanet]	990 / 7739
22	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
23	(OMIM)	White eyebrows and eyelashes		3 / 7739
24	(OMIM)	White hair with scattered black tufts		1 / 7739
25	(HPO:0012758)	Neurodevelopmental delay	Frequent [Orphanet]	949 / 7739
26	(OMIM)	Normal iris pigmentation		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Witkop (1979) reported 2 sibs born with white hair, some black locks, and depigmented skin with some brown spots on it. In addition, the infants were handicapped by nystagmus, photophobia, retinal depigmentation, and deafness. He called this disorder ... Witkop (1979) reported 2 sibs born with white hair, some black locks, and depigmented skin with some brown spots on it. In addition, the infants were handicapped by nystagmus, photophobia, retinal depigmentation, and deafness. He called this disorder the black lock-albinism-deafness syndrome (BADS). O'Doherty and Gorlin (1988) presented photographs of a striking patient who had a nearly normal iris pigmentation but white hair and white eyebrows and eyelashes with scattered black tufts resembling ermine (the ermine is born with brown fur which changes at about age 9 months, when it grows its characteristic winter coat for camouflage in a snowy environment, but with the black tip of its tail always preserved). The patient had sensorineural hearing loss and mild mental retardation. On various areas of the body, there was depigmentation described as 'marked vitiligo.' There were no findings in the family that assisted with the possible inheritance. O'Doherty and Gorlin (1988) referred to descriptions of oculocutaneous albinism with black locks and congenital sensorineural hearing loss (BADS syndrome) occurring in the brother and sister described by Witkop (1979). They also referred to another pair of male and female sibs with normal pigmentation of the irides and eyegrounds and with depigmentation changes like those of vitiligo (193200). The latter was thought to represent an autoimmune disorder. The authors noted the association of vitiligo and deafness (see 606579, 221350) and of pigmentary abnormalities and deafness (as in 300700). Zarate et al. (2009) reported a 9-year-old girl, born to healthy nonconsanguineous parents, who had evenly pigmented fair skin and brown hair at birth but who developed skin patches of hyper- and hypopigmentation between 6 months and 12 months of age, as well as progressive replacement of her brown hair by white hair with black patches. She also exhibited developmental delay, microcephaly, and hypotonia; MRI at ages 7 months and 23 months revealed delayed myelination of the corpus callosum that showed improvement on the second MRI, decreased central white matter, and diffuse small calcifications within the periventricular white matter but no tubers or masses. In childhood she developed astigmatism requiring glasses, but ophthalmologic examination was otherwise normal. She had an abnormal hearing screen at 4 years of age, and audiogram at age 9 showed bilateral mild to moderate sensorineural hearing loss at all frequencies. At 9 years of age, her height, weight, and head circumference were all below the fifth centile for age, she had global developmental delay, and hypotonia was still present but less severe. She also had bilateral fifth finger clinodactyly, mild 2/3 toe syndactyly, a wide-based slow gait, mildly decreased muscle tone, and normal strength. On her skin there were multiple patches of well-demarcated hyper- and hypopigmentation covering the entire body that did not follow Blaschko lines and were randomly distributed. The pigmentation changes appeared to be quite stable over time, since some of the changes seen in photographs at age 18 months and 4 years were still identifiable at 9 years of age. Her hair was white with a few black patches but no alopecia. Microscopic examination of skin samples from hypopigmented, hyperpigmented, and normal skin showed melanin pigment in all samples but marked variation in the amount of pigment present; there was no inflammation and no pigmentary incontinence. Electron microscopy of epidermocytes and melanocytes showed that melanosomes in both cell types were smaller and more variable in size and shape than normal, and pigment was unevenly distributed in the granules; absent pigment incontinence in the dermis was confirmed. Muscle biopsy at age 29 months showed nonuniform myofiber atrophy and hypertrophy and was suggestive of chronic lower motor unit disorder, with normal muscle ultrastructure on electron microscopy. Mitochondrial functional studies from the muscle biopsy were normal. Zarate et al. (2009) noted that the phenotype in this patient was very similar to that described by O'Doherty and Gorlin (1988).

Symptoms & Signs

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