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DOORS syndrome(DOORS)

MedGen UID:
208648
Concept ID:
C0795934
Disease or Syndrome
Synonyms: BRACHYDACTYLY DUE TO ABSENCE OF DISTAL PHALANGES; Deafness onychodystrophy osteodystrophy and mental retardation syndrome; DEAFNESS, ONYCHODYSTROPHY, OSTEODYSTROPHY, IMPAIRED INTELLECTUAL DEVELOPMENT, AND SEIZURES SYNDROME; Digitorenocerebral syndrome; DOORS; DRC SYNDROME; ERONEN SYNDROME
SNOMED CT: DOORS syndrome (719800009); Autosomal recessive deafness onychodystrophy syndrome (719800009); DOOR syndrome (719800009); Deafness, onychodystrophy, osteodystrophy, intellectual disability syndrome (719800009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TBC1D24 (16p13.3)
 
Monarch Initiative: MONDO:0009079
OMIM®: 220500
Orphanet: ORPHA79500

Disease characteristics

Excerpted from the GeneReview: TBC1D24-Related Disorders
TBC1D24-related disorders comprise a continuum of features that were originally described as distinct, recognized phenotypes: DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures). Profound sensorineural hearing loss, onychodystrophy, osteodystrophy, intellectual disability / developmental delay, and seizures. Familial infantile myoclonic epilepsy (FIME). Early-onset myoclonic seizures, focal epilepsy, dysarthria, and mild-to-moderate intellectual disability. Progressive myoclonus epilepsy (PME). Action myoclonus, tonic-clonic seizures, progressive neurologic decline, and ataxia. Early-infantile epileptic encephalopathy 16 (EIEE16). Epileptiform EEG abnormalities which themselves are believed to contribute to progressive disturbance in cerebral function. Autosomal recessive nonsyndromic hearing loss, DFNB86. Profound prelingual deafness. Autosomal dominant nonsyndromic hearing loss, DFNA65. Slowly progressive deafness with onset in the third decade, initially affecting the high frequencies. [from GeneReviews]
Authors:
Bettina E Mucha  |  Raoul CM Hennekam  |  Sanjay Sisodiya, et. al.   view full author information

Additional description

From OMIM
DOOR syndrome is an autosomal recessive disorder characterized by Deafness, Onychodystrophy, Osteodystrophy, and mental Retardation. Cantwell (1975) suggested this designation for the disorder, which can also include triphalangeal thumbs, seizures, and abnormal dermatoglyphics. See also DDOD syndrome (124480), which shows autosomal dominant inheritance of congenital deafness and onychodystrophy without mental retardation. See also OORS syndrome (619356), caused by mutation in the PIGF gene (600153), which shows overlapping features with the notable lack of deafness.  http://www.omim.org/entry/220500

Clinical features

From HPO
Renal agenesis
MedGen UID:
154237
Concept ID:
C0542519
Congenital Abnormality
Agenesis, that is, failure of the kidney to develop during embryogenesis and development.
Cystic renal dysplasia
MedGen UID:
322533
Concept ID:
C1834931
Congenital Abnormality
Increased urine alpha-ketoglutarate concentration
MedGen UID:
868516
Concept ID:
C4022915
Finding
A greater than normal concentration of 2-oxoglutaric acid in the urine.
Triphalangeal thumb
MedGen UID:
66029
Concept ID:
C0241397
Congenital Abnormality
A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.
Long thumb
MedGen UID:
322130
Concept ID:
C1833148
Finding
Length of the thumb is greater than normal.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Short 5th finger
MedGen UID:
334269
Concept ID:
C1842878
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the fifth finger, also known as the little finger.
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Bilateral sensorineural hearing impairment
MedGen UID:
96788
Concept ID:
C0452138
Disease or Syndrome
A bilateral form of sensorineural hearing impairment.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Polyneuropathy
MedGen UID:
57502
Concept ID:
C0152025
Disease or Syndrome
A generalized disorder of peripheral nerves.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
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.
Dandy-Walker syndrome
MedGen UID:
4150
Concept ID:
C0010964
Disease or Syndrome
Dandy-Walker malformation is defined by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. Affected individuals often have motor deficits such as delayed motor development, hypotonia, and ataxia; about half have mental retardation and some have hydrocephalus. DWM is a heterogeneous disorder. The low empiric recurrence risk of approximately 1 to 2% for nonsyndromic DWM suggests that mendelian inheritance is unlikely (summary by Murray et al., 1985).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Low anterior hairline
MedGen UID:
331280
Concept ID:
C1842366
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Everted lower lip vermilion
MedGen UID:
344003
Concept ID:
C1853246
Finding
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
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).
Anonychia
MedGen UID:
120563
Concept ID:
C0265998
Congenital Abnormality
Congenital anonychia is defined as the absence of fingernails and toenails. Anonychia and its milder phenotypic variant, hyponychia, usually occur as a feature of genetic syndromes, in association with significant skeletal and limb anomalies. Isolated nonsyndromic congenital anonychia/hyponychia is a rare entity that usually follows autosomal recessive inheritance with variable expression, even within a given family. The nail phenotypes observed range from no nail field to a nail field of reduced size with an absent or rudimentary nail (summary by Bruchle et al., 2008). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-4 (NDNC4). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Hypoplastic toenails
MedGen UID:
332409
Concept ID:
C1837279
Finding
Underdevelopment of the toenail.
Hypoplastic fingernail
MedGen UID:
347304
Concept ID:
C1856786
Finding
Underdevelopment of a fingernail.
Thickened nuchal skin fold
MedGen UID:
324644
Concept ID:
C1836940
Finding
A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold (NF) measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. An NF measurement greater than 5 mm at 14 to 17+6 weeks of gestation, or 6 mm at 18 to 28 weeks has been associated with a markedly increased risk for Down syndrome.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as visual perception below 3/60 and/or a visual field of no greater than 10 degrees in radius around central fixation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Campeau PM, Hennekam RC; DOORS syndrome collaborative group
Am J Med Genet C Semin Med Genet 2014 Sep;166C(3):327-32. Epub 2014 Aug 28 doi: 10.1002/ajmg.c.31412. PMID: 25169651

Recent clinical studies

Etiology

Gao X, Dai P, Yuan YY
Hum Genet 2022 Apr;141(3-4):821-838. Epub 2021 Jul 7 doi: 10.1007/s00439-021-02310-2. PMID: 34232384
Mucha BE, Banka S, Ajeawung NF, Molidperee S, Chen GG, Koenig MK, Adejumo RB, Till M, Harbord M, Perrier R, Lemyre E, Boucher RM, Skotko BG, Waxler JL, Thomas MA, Hodge JC, Gecz J, Nicholl J, McGregor L, Linden T, Sisodiya SM, Sanlaville D, Cheung SW, Ernst C, Campeau PM
Genet Med 2019 May;21(5):1058-1064. Epub 2018 Sep 24 doi: 10.1038/s41436-018-0290-3. PMID: 30245510
Campeau PM, Hennekam RC; DOORS syndrome collaborative group
Am J Med Genet C Semin Med Genet 2014 Sep;166C(3):327-32. Epub 2014 Aug 28 doi: 10.1002/ajmg.c.31412. PMID: 25169651

Diagnosis

Gao X, Dai P, Yuan YY
Hum Genet 2022 Apr;141(3-4):821-838. Epub 2021 Jul 7 doi: 10.1007/s00439-021-02310-2. PMID: 34232384
Beauregard-Lacroix E, Pacheco-Cuellar G, Ajeawung NF, Tardif J, Dieterich K, Dabir T, Vind-Kezunovic D, White SM, Zadori D, Castiglioni C, Tranebjærg L, Tørring PM, Blair E, Wisniewska M, Camurri MV, van Bever Y, Molidperee S, Taylor J, Dionne-Laporte A, Sisodiya SM, Hennekam RCM, Campeau PM
Genet Med 2021 Jan;23(1):149-154. Epub 2020 Sep 2 doi: 10.1038/s41436-020-00950-9. PMID: 32873933
Danarti R, Rahmayani S, Wirohadidjojo YW, Chen W
Eur J Dermatol 2020 Aug 1;30(4):404-407. doi: 10.1684/ejd.2020.3850. PMID: 32969800
Campeau PM, Hennekam RC; DOORS syndrome collaborative group
Am J Med Genet C Semin Med Genet 2014 Sep;166C(3):327-32. Epub 2014 Aug 28 doi: 10.1002/ajmg.c.31412. PMID: 25169651
Campeau PM, Kasperaviciute D, Lu JT, Burrage LC, Kim C, Hori M, Powell BR, Stewart F, Félix TM, van den Ende J, Wisniewska M, Kayserili H, Rump P, Nampoothiri S, Aftimos S, Mey A, Nair LD, Begleiter ML, De Bie I, Meenakshi G, Murray ML, Repetto GM, Golabi M, Blair E, Male A, Giuliano F, Kariminejad A, Newman WG, Bhaskar SS, Dickerson JE, Kerr B, Banka S, Giltay JC, Wieczorek D, Tostevin A, Wiszniewska J, Cheung SW, Hennekam RC, Gibbs RA, Lee BH, Sisodiya SM
Lancet Neurol 2014 Jan;13(1):44-58. Epub 2013 Nov 29 doi: 10.1016/S1474-4422(13)70265-5. PMID: 24291220Free PMC Article

Prognosis

Aprile D, Fruscione F, Baldassari S, Fadda M, Ferrante D, Falace A, Buhler E, Sartorelli J, Represa A, Baldelli P, Benfenati F, Zara F, Fassio A
Cell Death Differ 2019 Nov;26(11):2464-2478. Epub 2019 Mar 11 doi: 10.1038/s41418-019-0313-x. PMID: 30858606Free PMC Article
Stražišar BG, Neubauer D, Paro Panjan D, Writzl K
Eur J Paediatr Neurol 2015 Mar;19(2):251-6. Epub 2014 Dec 20 doi: 10.1016/j.ejpn.2014.12.011. PMID: 25557349
Azaiez H, Booth KT, Bu F, Huygen P, Shibata SB, Shearer AE, Kolbe D, Meyer N, Black-Ziegelbein EA, Smith RJ
Hum Mutat 2014 Jul;35(7):819-23. Epub 2014 May 6 doi: 10.1002/humu.22557. PMID: 24729539Free PMC Article

Clinical prediction guides

Aprile D, Fruscione F, Baldassari S, Fadda M, Ferrante D, Falace A, Buhler E, Sartorelli J, Represa A, Baldelli P, Benfenati F, Zara F, Fassio A
Cell Death Differ 2019 Nov;26(11):2464-2478. Epub 2019 Mar 11 doi: 10.1038/s41418-019-0313-x. PMID: 30858606Free PMC Article
Mucha BE, Banka S, Ajeawung NF, Molidperee S, Chen GG, Koenig MK, Adejumo RB, Till M, Harbord M, Perrier R, Lemyre E, Boucher RM, Skotko BG, Waxler JL, Thomas MA, Hodge JC, Gecz J, Nicholl J, McGregor L, Linden T, Sisodiya SM, Sanlaville D, Cheung SW, Ernst C, Campeau PM
Genet Med 2019 May;21(5):1058-1064. Epub 2018 Sep 24 doi: 10.1038/s41436-018-0290-3. PMID: 30245510
Poulat AL, Ville D, de Bellescize J, André-Obadia N, Cacciagli P, Milh M, Villard L, Lesca G
Epilepsy Res 2015 Mar;111:72-7. Epub 2015 Jan 25 doi: 10.1016/j.eplepsyres.2015.01.008. PMID: 25769375
Stražišar BG, Neubauer D, Paro Panjan D, Writzl K
Eur J Paediatr Neurol 2015 Mar;19(2):251-6. Epub 2014 Dec 20 doi: 10.1016/j.ejpn.2014.12.011. PMID: 25557349
Azaiez H, Booth KT, Bu F, Huygen P, Shibata SB, Shearer AE, Kolbe D, Meyer N, Black-Ziegelbein EA, Smith RJ
Hum Mutat 2014 Jul;35(7):819-23. Epub 2014 May 6 doi: 10.1002/humu.22557. PMID: 24729539Free PMC Article

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