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Anophthalmia plus syndrome

General Information (adopted from Orphanet):

Synonyms, Signs:	MICROPHTHALMIA WITH FACIAL CLEFTING ANOPHTHALMIA-PLUS SYNDROME Fryns microphthalmia syndrome
Number of Symptoms	28
OrphanetNr:	1104
OMIM Id:	600776
ICD-10:	Q02
UMLs:	C1833339
MeSH:	C537767
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	4 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Antenatal Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
-Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
-Rare developmental defect during embryogenesis

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000119)	Abnormality of the genitourinary system		34 / 7739
2	(HPO:0000366)	Abnormality of the nose	Frequent [Orphanet]	56 / 7739
3	(HPO:0000581)	Blepharophimosis	Occasional [Orphanet]	197 / 7739
4	(HPO:0002006)	Facial cleft	Frequent [Orphanet]	25 / 7739
5	(HPO:0000204)	Cleft upper lip	Frequent [Orphanet]	193 / 7739
6	(HPO:0000174)	Abnormality of the palate	Frequent [Orphanet]	298 / 7739
7	(HPO:0000453)	Choanal atresia	Frequent [Orphanet]	76 / 7739
8	(HPO:0000316)	Hypertelorism	Frequent [Orphanet]	644 / 7739
9	(HPO:0000528)	Anophthalmia		42 / 7739
10	(HPO:0000625)	Cleft eyelid	Occasional [Orphanet]	31 / 7739
11	(HPO:0000568)	Microphthalmia		183 / 7739
12	(HPO:0002744)	Bilateral cleft lip and palate		7 / 7739
13	(HPO:0008056)	Aplasia/Hypoplasia affecting the eye	Very frequent [Orphanet]	142 / 7739
14	(HPO:0000612)	Iris coloboma	Occasional [Orphanet]	116 / 7739
15	(HPO:0009906)	Aplasia/Hypoplasia of the earlobes	Occasional [Orphanet]	41 / 7739
16	(HPO:0000400)	Macrotia		108 / 7739
17	(HPO:0000357)	Abnormal location of ears	Frequent [Orphanet]	328 / 7739
18	(HPO:0000925)	Abnormality of the vertebral column		20 / 7739
19	(HPO:0002414)	Spina bifida	Occasional [Orphanet]	47 / 7739
20	(HPO:0009466)	Radial deviation of finger	Occasional [Orphanet]	101 / 7739
21	(HPO:0003422)	Vertebral segmentation defect	Occasional [Orphanet]	95 / 7739
22	(HPO:0010305)	Absence of the sacrum	Occasional [Orphanet]	17 / 7739
23	(OMIM)	Open sacral neural tube defect		1 / 7739
24	(OMIM)	Bilateral anophthalmia		1 / 7739
25	(OMIM)	Absent ear lobule		1 / 7739
26	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
27	(OMIM)	Uterus unicornis		1 / 7739
28	(OMIM)	Bilateral lateral facial cleft		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Although primary anophthalmia has been documented as a manifestation of several mental retardation/congenital anomaly (MCA) syndromes, as reviewed by Leichtman et al. (1994), the nosology of this group of disorders is confusing. Fryns et al. (1995) described an ... Although primary anophthalmia has been documented as a manifestation of several mental retardation/congenital anomaly (MCA) syndromes, as reviewed by Leichtman et al. (1994), the nosology of this group of disorders is confusing. Fryns et al. (1995) described an apparently distinct 'anophthalmia-plus' syndrome in sibs. The index patient was a female fetus at 17 weeks' gestation with bilateral anophthalmia, bilateral cleft lip/cleft palate, macrotia with bilateral lateral facial cleft, large open sacral neural tube defect, and uterus unicornis. The parents were normal and nonconsanguineous with an unremarkable family history. Their first child, a 4-year-old boy, was normal. The second child, a 2.5-year-old boy, had bilateral clinical anophthalmia and an abnormal left ear with absent lobule as the sole additional anomaly. Warburg et al. (1997) described a patient with bilateral extreme microphthalmia and bilateral congenital glaucoma, bilateral medial oblique facial cleft ending in lid colobomas, bilateral stenosis of the choanae, bifid uvula, frontal encephalocele, and premature craniosynostosis. They suggested that this was an example of the Fryns anophthalmia syndrome, which may be an autosomal recessive disorder, although intrauterine environmental factors cannot be excluded. Wiltshire et al. (2003) reported a boy with a nasal deformity, choanal atresia, bifid uvula, severe bilateral microphthalmia, and a facial cleft who showed regression of development at the age of 2 years with subsequent improvement. Akalin et al. (2005) reported a male infant, born of consanguineous parents, with left-sided anophthalmia and right-sided microphthalmia with bilateral partial fusion of the eyelids, bilateral cleft lip and palate with nasal deformity, and clinodactyly of the right fourth toe. The patient was noted to have elevated serum levels of thyroid-stimulating hormone; thyroid ultrasonography revealed bilateral hyperplasia with no cysts or nodules. Akalin et al. (2005) concluded that primary hypothyroidism is an important additional feature of the 'anophthalmia-plus' syndrome. Makhoul et al. (2007) described a male infant, born of nonconsanguineous parents, who had bilateral cleft palate and lip, mild microphthalmia with iris coloboma and glaucoma of the right eye, and blepharophimosis with severe microphthalmia of the left eye. Spine x-ray and MRI revealed first sacral hemivertebra with spina bifida, and agenesis of the second through fifth sacral vertebrae and coccyx, with caudal tethering of the spinal cord at L3, filum terminalis lipoma, and a syringomyelia. Brain ultrasound and MRI showed hypoplasia of corpus callosum with mild dilation of the lateral ventricles; orbital MRI showed a posteriorly located lens of the left eye and a split vitreous body in the right eye, suggestive of primary hyperplastic vitreous. In contrast to the patient reported by Akalin et al. (2005), this patient had normal serum levels of free thyroxine, TSH, and cortisol. Makhoul et al. (2007) stated that this case supported the notion of anophthalmia-plus as a distinct syndrome. Ozalp et al. (2008) reported a 26-week female fetus with bilateral clinical anophthalmia, agenesis of the upper lip and palate, cerebral ventricular dilation, adrenal hypoplasia, and single umbilical artery. A neural tube defect was not detected. Histologic examination of adrenal tissue showed a focal pseudofollicular pattern, autolytic changes, and neuroblastic clusters in the adrenal cortex. The consanguineous Turkish parents had a healthy 7-year-old daughter from their first pregnancy; a male infant from their second pregnancy had frontal bossing, bilateral anophthalmia, total agenesis of the upper lip, and rudimentary nostrils, and died at 9 weeks of age due to respiratory and cardiac failure. Ozalp et al. (2008) stated that this was the first report of adrenal hypoplasia in Fryns anophthalmia-plus syndrome.

Symptoms & Signs

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