Welcome to PhenoDis

Ablepharon macrostomia syndrome

General Information (adopted from Orphanet):

Synonyms, Signs:	AMS
Number of Symptoms	57
OrphanetNr:	920
OMIM Id:	200110
ICD-10:	Q87.0
UMLs:	C1860224
MeSH:	C535557
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	15 cases [Orphanet]
Inheritance:	Autosomal dominant [Orphanet]
Age of onset:	Antenatal Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Genetic multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
-Rare genetic disease
Microblepharon - ablephara
-Rare eye disease
-Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome - variable intellectual deficit
-Rare developmental defect during embryogenesis
Orofacial clefting syndrome
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare maxillo-facial surgical disease
-Rare otorhinolaryngologic disease
Syndromic developmental defect of the eye
-Rare developmental defect during embryogenesis
-Rare eye disease
-Rare genetic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000054)	Micropenis	Frequent [Orphanet]	257 / 7739
2	(HPO:0000035)	Abnormality of the testis	Frequent [Orphanet]	296 / 7739
3	(HPO:0000062)	Ambiguous genitalia	Frequent [Orphanet]	74 / 7739
4	(HPO:0000327)	Hypoplasia of the maxilla	Frequent [Orphanet]	129 / 7739
5	(HPO:0000316)	Hypertelorism		644 / 7739
6	(HPO:0005280)	Depressed nasal bridge	Occasional [Orphanet]	381 / 7739
7	(HPO:0002223)	Absent eyebrow		21 / 7739
8	(HPO:0000188)	Short upper lip	rare [HPO:skoehler]	8 / 7739
9	(HPO:0009553)	Abnormality of the hairline	Occasional [Orphanet]	30 / 7739
10	(HPO:0000233)	Thin vermilion border	Occasional [Orphanet]	124 / 7739
11	(HPO:0000561)	Absent eyelashes		18 / 7739
12	(HPO:0011224)	Ablepharon		2 / 7739
13	(HPO:0000463)	Anteverted nares	Frequent [Orphanet]	305 / 7739
14	(HPO:0100840)	Aplasia/Hypoplasia of the eyebrow	Very frequent [Orphanet]	117 / 7739
15	(HPO:0200102)	Sparse or absent eyelashes	Very frequent [Orphanet]	64 / 7739
16	(HPO:0000492)	Abnormality of the eyelid	Very frequent [Orphanet]	41 / 7739
17	(HPO:0000691)	Microdontia	Frequent [Orphanet]	104 / 7739
18	(HPO:0000272)	Malar flattening	Very frequent [Orphanet]	277 / 7739
19	(HPO:0000430)	Underdeveloped nasal alae	Very frequent [Orphanet]	90 / 7739
20	(HPO:0001126)	Cryptophthalmos		3 / 7739
21	(HPO:0005105)	Abnormal nasal morphology		114 / 7739
22	(HPO:0000154)	Wide mouth	Very frequent [Orphanet]	137 / 7739
23	(HPO:0000481)	Abnormality of the cornea	Occasional [Orphanet]	124 / 7739
24	(HPO:0000545)	Myopia	Frequent [Orphanet]	286 / 7739
25	(HPO:0000572)	Visual loss	Frequent [Orphanet]	272 / 7739
26	(HPO:0011267)	Microtia, third degree		1 / 7739
27	(HPO:0008772)	Aplasia/Hypoplasia of the external ear	Very frequent [Orphanet]	67 / 7739
28	(HPO:0000372)	Abnormality of the auditory canal	Occasional [Orphanet]	49 / 7739
29	(HPO:0000365)	Hearing impairment	Frequent [Orphanet]	539 / 7739
30	(HPO:0000750)	Delayed speech and language development		197 / 7739
31	(HPO:0002167)	Neurological speech impairment	Very frequent [Orphanet]	308 / 7739
32	(HPO:0100783)	Breast aplasia	Frequent [Orphanet]	19 / 7739
33	(HPO:0006709)	Aplasia/Hypoplasia of the nipples	Frequent [Orphanet]	28 / 7739
34	(HPO:0100490)	Camptodactyly of finger	Frequent [Orphanet]	212 / 7739
35	(HPO:0001762)	Talipes equinovarus	rare [HPO:skoehler]	309 / 7739
36	(HPO:0001770)	Toe syndactyly	Occasional [Orphanet]	149 / 7739
37	(HPO:0001537)	Umbilical hernia	Frequent [Orphanet]	206 / 7739
38	(HPO:0001539)	Omphalocele	Occasional [Orphanet]	102 / 7739
39	(HPO:0002933)	Ventral hernia		2 / 7739
40	(HPO:0004325)	Decreased body weight	Occasional [Orphanet]	492 / 7739
41	(HPO:0100678)	Premature skin wrinkling	Frequent [Orphanet]	25 / 7739
42	(HPO:0000958)	Dry skin	Frequent [Orphanet]	152 / 7739
43	(HPO:0001582)	Redundant skin	Very frequent [Orphanet]	51 / 7739
44	(HPO:0001000)	Abnormality of skin pigmentation	Occasional [Orphanet]	105 / 7739
45	(HPO:0000963)	Thin skin	Frequent [Orphanet]	96 / 7739
46	(HPO:0002213)	Fine hair	Very frequent [Orphanet]	77 / 7739
47	(HPO:0001006)	Hypotrichosis	Very frequent [Orphanet]	219 / 7739
48	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
49	(OMIM)	Microblepharon		1 / 7739
50	(HPO:0012758)	Neurodevelopmental delay	Frequent [Orphanet]	949 / 7739
51	(OMIM)	Absent lanugo		2 / 7739
52	(OMIM)	Coarse skin		2 / 7739
53	(OMIM)	External ears rudimentary		1 / 7739
54	(OMIM)	Redundant folds		1 / 7739
55	(OMIM)	Shape abnormal		1 / 7739
56	(OMIM)	Zygomatic arches absent		1 / 7739
57	(HPO:0012815)	Hypoplastic female external genitalia	Frequent [Orphanet]	36 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

McCarthy and West (1977) reported 2 unrelated male children with absent eyelids, eyebrows, and eyelashes; fusion defects of the mouth; rudimentary external ears; ambiguous genitalia; absent or rudimentary nipples; coarse, dry skin with redundant skin folds; and delayed ... McCarthy and West (1977) reported 2 unrelated male children with absent eyelids, eyebrows, and eyelashes; fusion defects of the mouth; rudimentary external ears; ambiguous genitalia; absent or rudimentary nipples; coarse, dry skin with redundant skin folds; and delayed development of expressive language. Jackson et al. (1988) provided follow-up at age 12 years on the second case of McCarthy and West (1977). They pointed out another feature of the disorder, namely, absence of the zygomatic arches. Possible autosomal recessive inheritance was proposed because of a postulated relationship to the disorder in monozygotic twins from a consanguineous marriage: one twin had bilateral cryptophthalmos and the other had cryptophthalmos on the left and ablepharon on the right (Azevedo et al., 1973). Hornblass and Reifler (1985) described a 10-day-old infant with total absence of the upper and lower eyelids, failure of lip fusion resulting in an enlarged, fish-like mouth, abnormally shaped ears and nose, absence of lanugo, ventral hernia, and ambiguous genitalia. They reconstructed the eyelids in a 3-stage procedure and later the child underwent successful reconstruction of the mouth. Hornblass and Reifler (1985) drew attention to the presence of vestigial eyelid structures, suggesting that the true nature of the eyelid deformity in this syndrome may be severe microblepharon rather than ablepharon. Ferraz et al. (2000) described an infant with ablepharon-macrostomia syndrome, the sister of a previously reported affected female (Cruz et al., 1995). Manifestations of the syndrome included severe shortness of the eyelids, low nasal bridge with hypoplastic and anteverted nostrils, macrostomia, small ears, absence of nipples, and absence of lanugo. The father had more mild abnormalities of the eyelids, eyebrows, and ears. The authors suggested that this family supports autosomal dominant inheritance with variable expression. Stevens and Sargent (2002) reported 3 new cases, gave a 10-year follow-up of a newborn reported in an abstract by Markouizos et al. (1990), and reviewed the findings in the 4 other reported cases. All of the patients had absent hair, brows, and lashes, absent or short eyelids, macrostomia, ear anomalies, redundant skin, and abnormal genitalia. Many had persistent visual problems, often related to early corneal exposure. Hearing loss, poor hair growth, finger contractures, and growth retardation were also chronic problems. Developmental impairment was present in two-thirds of patients but was usually mild. Their series included the first reported adult patient, a 27-year-old woman. She had no scalp hair, eyelids, eyebrows, or eyelashes at birth. She had macrostomia and tiny 'rosebud' ears. There was camptodactyly and mild syndactyly of fingers 2 to 5 bilaterally and ambiguous genitalia. Because of distinctive clinical manifestations that are shared in common by AMS and Barber-Say syndrome (209885), some have suggested that they may represent defects in the same gene (Mazzanti et al., 1998). Stevens and Sargent (2002) suggested that their experience provided evidence that AMS is distinct from Barber-Say syndrome. Common features of the 2 syndromes are macrostomia, abnormal ears and nose, hypoplastic nipples, sparse eyebrows and eyelashes, and redundant skin. Distinguishing features include ablepharon in AMS versus ectropion in Barber-Say syndrome and marked hypertrichosis in Barber-Say syndrome. Genital abnormalities are much more severe in AMS. Brancati et al. (2004) contributed to the characterization of the AMS phenotype in adulthood. They reported an Italian woman in whom the diagnosis was made at the age of 46 years. At birth, absent eyelashes and eyebrows, with slight and asymmetric vertical shortening of upper and lower eyelids, and abnormal ears with rudimentary cartilage were described. At the age of 14 years, when surgical repair of the eyelids was performed, alae nasi and malar hypoplasia, absent zygomatic arches, macrostomia, and small chin were noted. At 22 years of age, chin and breast hypoplasia were treated by plastic surgery, and hypoplasia of the zygomatic arches was remodeled some months later, by implantation of subcutaneous prostheses. At 31 years of age, surgical reconstruction of external ears was attempted. On evaluation at age 46 years, the findings included partial cutaneous syndactyly with camptodactyly of the fifth fingers, particularly on the left. Other finger bone anomalies included short left third, fourth, and fifth and right fourth and fifth metacarpal bones. Audiograms showed bilateral high frequency hearing loss. Developmental milestones were considered normal as well as intelligence at the time of examination. Menarche occurred at 12 years of age. The findings were compared to those in 13 other patients: 11 aged newborn to 12 years, one aged 25 years (Ferraz et al., 2000), and one aged 27 years (Stevens and Sargent, 2002).

Symptoms & Signs

	Field	Query
	Disease
	Symptom