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Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3(EEC3)

MedGen UID:
347666
Concept ID:
C1858562
Disease or Syndrome
Synonyms: Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3; Ectrodactyly, Ectodermal Dysplasia, Cleft Lip/Palate Syndrome 3 (EEC3); Ectrodactyly, Ectodermal Dysplasia, Clefting Syndrome; Ectrodactyly, Ectodermal Dysplasia, Clefting Syndrome Type 3 (EEC3); EEC SYNDROME 3
 
Gene (location): TP63 (3q28)
 
Monarch Initiative: MONDO:0011428
OMIM®: 604292

Disease characteristics

Excerpted from the GeneReview: TP63-Related Disorders
The TP63-related disorders comprise six overlapping phenotypes: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome). Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3). Limb-mammary syndrome. Split-hand/foot malformation type 4 (SHFM4). Isolated cleft lip/cleft palate (orofacial cleft 8). Individuals typically have varying combinations of ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, hypoplastic breasts and/or nipples, and hypospadias. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring, and alopecia, trismus, and excessive freckling. [from GeneReviews]
Authors:
V Reid Sutton  |  Hans van Bokhoven   view full author information

Additional description

From OMIM
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome-3 (ECC3) is an autosomal dominant disorder comprising absence of the central parts of the hands and feet, resulting in split-hand/foot malformation, ectodermal dysplasia, and cleft lip with or without cleft palate (summary by Maas et al., 1996). Also see EEC1 (129900), which has been mapped to chromosome 7q11.  http://www.omim.org/entry/604292

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Ureterocele
MedGen UID:
21778
Concept ID:
C0041960
Acquired Abnormality
A ureterocele is a congenital saccular dilatation of the distal segment of the ureter.
Urethral stenosis
MedGen UID:
12016
Concept ID:
C0041974
Finding
Abnormal narrowing of the urethra.
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Diverticulum of bladder
MedGen UID:
57625
Concept ID:
C0156273
Finding
Diverticulum (sac or pouch) in the wall of the urinary bladder.
Hydroureter
MedGen UID:
101073
Concept ID:
C0521620
Anatomical Abnormality
The distention of the ureter with urine.
Renal agenesis
MedGen UID:
154237
Concept ID:
C0542519
Congenital Abnormality
Agenesis, that is, failure of the kidney to develop during embryogenesis and development.
Megacystis
MedGen UID:
343318
Concept ID:
C1855311
Finding
Dilatation of the bladder postnatally.
Transverse vaginal septum
MedGen UID:
341032
Concept ID:
C1856006
Finding
A rare vaginal malformation characterized by the presence of a complete or incomplete transverse septum at any level of the vagina (most frequently the upper or middle third), resulting from incomplete fusion between the Müllerian duct component and the urogenital sinus component of the vagina during embryogenesis. The condition is only rarely diagnosed in neonates or infants, unless it causes significant hydromucocolpos. Complete septa present with primary amenorrhea, cyclic pelvic pain, dyspareunia, or a pelvic mass consisting of accumulated menstrual blood, while incomplete septa may lead to dyspareunia and dysmenorrhea.
Duplicated collecting system
MedGen UID:
346936
Concept ID:
C1858565
Anatomical Abnormality
A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice.
Renal dysplasia
MedGen UID:
760690
Concept ID:
C3536714
Congenital Abnormality
The presence of developmental dysplasia of the kidney.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Ectrodactyly
MedGen UID:
78566
Concept ID:
C0265554
Congenital Abnormality
A condition in which middle parts of the hands and/or feet (digits and meta-carpals and -tarsals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic 3rd toe/fingers over absent 2nd or 3rd toes/fingers as far as oligo- or monodactyl hands and/or feet.
Toe syndactyly
MedGen UID:
75581
Concept ID:
C0265660
Congenital Abnormality
Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism".
Split foot
MedGen UID:
140919
Concept ID:
C0432028
Congenital Abnormality
A condition in which middle parts of the foot (toes and metatarsals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic 3rd toe over absent 2nd or 3rd toes as far as oligo- or monodactyl feet.
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middel fingers as far as oligo- or monodactyl hands.
Anal stenosis
MedGen UID:
82644
Concept ID:
C0262374
Anatomical Abnormality
Abnormal narrowing of the anal opening.
Anteriorly placed anus
MedGen UID:
333160
Concept ID:
C1838705
Finding
Anterior malposition of the anus.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Hypoplastic sacrum
MedGen UID:
370356
Concept ID:
C1970816
Finding
Abnormal nasopharynx morphology
MedGen UID:
871265
Concept ID:
C4025750
Anatomical Abnormality
A structural anomaly of the nasopharynx.
Blepharitis
MedGen UID:
598
Concept ID:
C0005741
Disease or Syndrome
Inflammation of the eyelids.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Congenital Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Choanal atresia
MedGen UID:
3395
Concept ID:
C0008297
Congenital Abnormality
Absence or abnormal closure of the choana (the posterior nasal aperture). Most embryologists believe that posterior choanal atresia results from a failure of rupture between the 35th and 38th day of fetal life of the partition which separates the bucconasal or buccopharyngeal membranes. The resultant choanal atresia may be unilateral or bilateral, bony or membranous, complete or incomplete. In over 90 per cent of cases the obstruction is bony, while in the remainder it is membranous. The bony type of atresia is commonly located 1-2 mm. anterior to the posterior edge of the hard palate, and the osseous septum varies in thickness from 1 to 10 mm. In the membranous form of choanal atresia the obstruction usually occurs further posteriorly. In approximately one third of cases the atresia is bilateral.
Cleft upper lip
MedGen UID:
40327
Concept ID:
C0008924
Congenital Abnormality
A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Dacryocystitis
MedGen UID:
3686
Concept ID:
C0010930
Disease or Syndrome
Inflammation of the nasolacrimal sac.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Xerostomia
MedGen UID:
22735
Concept ID:
C0043352
Disease or Syndrome
Dryness of the mouth due to salivary gland dysfunction.
Lacrimal duct stenosis
MedGen UID:
116054
Concept ID:
C0238300
Finding
Narrowing of a tear duct (lacrimal duct).
Microdontia
MedGen UID:
66008
Concept ID:
C0240340
Congenital Abnormality
Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth.
Sparse eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number of eyebrow hairs.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Absence of Stensen duct
MedGen UID:
347668
Concept ID:
C1858569
Finding
Depressed nasal tip
MedGen UID:
347214
Concept ID:
C1859717
Finding
Decreased distance from the nasal tip to the nasal base.
Selective tooth agenesis
MedGen UID:
370882
Concept ID:
C1970308
Congenital Abnormality
Agenesis specifically affecting one of the classes incisor, premolar, or molar.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Ectodermal dysplasia
MedGen UID:
8544
Concept ID:
C0013575
Disease or Syndrome
Ectodermal dysplasia is a group of conditions in which there is abnormal development of the skin, hair, nails, teeth, or sweat glands.
Nail pits
MedGen UID:
57463
Concept ID:
C0150993
Finding
Small (typically about 1 mm or less in size) depressions on the dorsal nail surface.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Hyperkeratosis
MedGen UID:
209030
Concept ID:
C0870082
Disease or Syndrome
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
Sparse eyelashes
MedGen UID:
375151
Concept ID:
C1843300
Finding
Decreased density/number of eyelashes.
Fair hair
MedGen UID:
336542
Concept ID:
C1849221
Finding
A lesser degree of hair pigmentation than would otherwise be expected.
Generalized hypopigmentation
MedGen UID:
340426
Concept ID:
C1849923
Finding
Facial hirsutism
MedGen UID:
337950
Concept ID:
C1850041
Finding
Excess facial hair.
Sparse pubic hair
MedGen UID:
388095
Concept ID:
C1858573
Finding
Reduced number or density of pubic hair.
Sparse axillary hair
MedGen UID:
348975
Concept ID:
C1858574
Finding
Reduced number or density of axillary hair.
Hypogonadotropic hypogonadism
MedGen UID:
82883
Concept ID:
C0271623
Disease or Syndrome
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones
Central diabetes insipidus
MedGen UID:
146919
Concept ID:
C0687720
Disease or Syndrome
Neurohypophyseal diabetes insipidus is a disorder of water balance. The body normally balances fluid intake with the excretion of fluid in urine. However, people with neurohypophyseal diabetes insipidus produce too much urine (polyuria), which causes them to be excessively thirsty (polydipsia). Affected people need to urinate frequently, which can disrupt daily activities and sleep.\n\nPeople with neurohypophyseal diabetes insipidus can quickly become dehydrated if they do not drink enough water. Dehydration can lead to constipation and dry skin. If the disorder is not treated, more serious complications of dehydration can occur. These include confusion, low blood pressure, seizures, and coma.\n\nNeurohypophyseal diabetes insipidus can be either acquired or familial. The acquired form is brought on by injuries, tumors, and other factors, and can occur at any time during life. The familial form is caused by genetic mutations; its signs and symptoms usually become apparent in childhood and worsen over time.\n\nNeurohypophyseal diabetes insipidus should not be confused with diabetes mellitus, which is much more common. Diabetes mellitus is characterized by high blood sugar (glucose) levels resulting from a shortage of the hormone insulin or an insensitivity to this hormone. Although neurohypophyseal diabetes insipidus and diabetes mellitus have some features in common, they are separate disorders with different causes.
Decreased response to growth hormone stimulation test
MedGen UID:
1784655
Concept ID:
C5539399
Finding
Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.
Hypoplastic nipples
MedGen UID:
98156
Concept ID:
C0432355
Congenital Abnormality
Underdevelopment of the nipple.
Blue irides
MedGen UID:
108297
Concept ID:
C0578626
Finding
A markedly blue coloration of the iris.

Recent clinical studies

Diagnosis

Brueggemann FB, Bartsch O
Clin Dysmorphol 2016 Apr;25(2):50-3. doi: 10.1097/MCD.0000000000000117. PMID: 26882220

Clinical prediction guides

Brueggemann FB, Bartsch O
Clin Dysmorphol 2016 Apr;25(2):50-3. doi: 10.1097/MCD.0000000000000117. PMID: 26882220

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