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Primordial dwarfism-immunodeficiency-lipodystrophy syndrome(PDIL)

MedGen UID:
1823971
Concept ID:
C5774198
Disease or Syndrome
Synonym: PDIL
 
Gene (location): PRIM1 (12q13.3)
 
Monarch Initiative: MONDO:0859276
OMIM®: 620005

Definition

Primordial dwarfism-immunodeficiency-lipodystrophy syndrome (PDIL) is characterized by pre- and postnatal growth restriction, with extreme microcephaly, short stature, and absence of subcutaneous fat. There is also significant hematologic/immune dysfunction, with hypo- or agammaglobulinemia, as well as lymphopenia, anemia, and thrombocytopenia, and most affected individuals succumb to infection in early childhood (Parry et al., 2020). [from OMIM]

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).
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
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.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
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.
Portal hypertension
MedGen UID:
9375
Concept ID:
C0020541
Disease or Syndrome
Increased pressure in the portal vein.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Severe postnatal growth retardation
MedGen UID:
347510
Concept ID:
C1857641
Finding
Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Exocrine pancreatic insufficiency
MedGen UID:
75647
Concept ID:
C0267963
Disease or Syndrome
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Macronodular cirrhosis
MedGen UID:
384466
Concept ID:
C2004456
Disease or Syndrome
A type of cirrhosis characterized by the presence of large regenerative nodules.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
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.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Absence of subcutaneous fat
MedGen UID:
69138
Concept ID:
C0241267
Finding
Lack of subcutaneous adipose tissue.
Isolated scaphocephaly
MedGen UID:
82712
Concept ID:
C0265534
Congenital Abnormality
Scaphocephaly is a subtype of dolichocephaly where the anterior and posterior aspects of the cranial vault are pointed (boat-shaped). Scaphocephaly is caused by a precocious fusion of sagittal suture without other associated synostosis.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
11 pairs of ribs
MedGen UID:
326950
Concept ID:
C1839731
Finding
Presence of only 11 pairs of ribs.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Developmental dysplasia of the hip
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Wheezing
MedGen UID:
21917
Concept ID:
C0043144
Sign or Symptom
A high-pitched whistling sound associated with labored breathing.
Pulmonary infiltrates
MedGen UID:
116009
Concept ID:
C0235896
Finding
A finding indicating the presence of an inflammatory or neoplastic cellular infiltrate in the lung parenchyma.
Chronic lung disease
MedGen UID:
196656
Concept ID:
C0746102
Disease or Syndrome
According to the definitions of the American and British Thoracic Societies, including pulmonary functional tests, X-rays, and CT scans for items such as fibrosis, bronchiectasis, bullae, emphysema, nodular or lymphomatous abnormalities.
Acute respiratory distress syndrome
MedGen UID:
1812214
Concept ID:
C2887484
Disease or Syndrome
Acute respiratory distress syndrome (ARDS) is defined as an acute disorder that starts within seven days of the inciting event and is characterized by bilateral lung infiltrates and severe progressive hypoxemia in the absence of any evidence of cardiogenic pulmonary edema. ARDS is defined by the patient's oxygen in arterial blood (PaO2) to the fraction of the oxygen in the inspired air (FiO2). These patients have a PaO2/FiO2 ratio of less than 300.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Decreased circulating IgA level
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Accessory spleen
MedGen UID:
75619
Concept ID:
C0266631
Congenital Abnormality
An accessory spleen is a round, iso-echogenic, homogenic and smooth structure and is seen as a normal variant mostly on the medial contour of the spleen, near the hilus or around the lower pole. This has no pathogenic relevance.
Severe B lymphocytopenia
MedGen UID:
350238
Concept ID:
C1863715
Finding
A severe form of B lymphocytopenia in which the count of B cells is very low or absent.
Decreased circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
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.
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.
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Depressed nasal tip
MedGen UID:
347214
Concept ID:
C1859717
Finding
Decreased distance from the nasal tip to the nasal base.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
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.

Professional guidelines

PubMed

Abdel-Salam GMH, Sayed ISM, Afifi HH, Abdel-Ghafar SF, Abouzaid MR, Ismail SI, Aglan MS, Issa MY, El-Bassyouni HT, El-Kamah G, Effat LK, Eid M, Zaki MS, Temtamy SA, Abdel-Hamid MS
Am J Med Genet A 2020 Jun;182(6):1407-1420. Epub 2020 Apr 8 doi: 10.1002/ajmg.a.61585. PMID: 32267100
Shelihan I, Ehresmann S, Magnani C, Forzano F, Baldo C, Brunetti-Pierri N, Campeau PM
Hum Genet 2018 Dec;137(11-12):905-909. Epub 2018 Oct 27 doi: 10.1007/s00439-018-1950-8. PMID: 30368667
Kones R
Drug Des Devel Ther 2011;5:325-80. Epub 2011 Jun 13 doi: 10.2147/DDDT.S14934. PMID: 21792295Free PMC Article

Recent clinical studies

Etiology

Wang F, Liu Y, Ni F, Jin J, Wu Y, Huang Y, Ye X, Shen X, Ying Y, Chen J, Chen R, Zhang Y, Sun X, Wang S, Xu X, Chen C, Guo J, Zhang D
Nat Commun 2022 Oct 5;13(1):5871. doi: 10.1038/s41467-022-33323-8. PMID: 36198708Free PMC Article
Mohammadian Khonsari N, Khashayar P, Shahrestanaki E, Kelishadi R, Mohammadpoor Nami S, Heidari-Beni M, Esmaeili Abdar Z, Tabatabaei-Malazy O, Qorbani M
Front Endocrinol (Lausanne) 2022;13:857930. Epub 2022 Mar 24 doi: 10.3389/fendo.2022.857930. PMID: 35399938Free PMC Article
O'Kelly AC, Michos ED, Shufelt CL, Vermunt JV, Minissian MB, Quesada O, Smith GN, Rich-Edwards JW, Garovic VD, El Khoudary SR, Honigberg MC
Circ Res 2022 Feb 18;130(4):652-672. Epub 2022 Feb 17 doi: 10.1161/CIRCRESAHA.121.319895. PMID: 35175837Free PMC Article
Kumariya S, Ubba V, Jha RK, Gayen JR
Autophagy 2021 Oct;17(10):2706-2733. Epub 2021 Jun 23 doi: 10.1080/15548627.2021.1938914. PMID: 34161185Free PMC Article
Tal R, Seifer DB
Am J Obstet Gynecol 2017 Aug;217(2):129-140. Epub 2017 Feb 21 doi: 10.1016/j.ajog.2017.02.027. PMID: 28235465

Diagnosis

O'Kelly AC, Michos ED, Shufelt CL, Vermunt JV, Minissian MB, Quesada O, Smith GN, Rich-Edwards JW, Garovic VD, El Khoudary SR, Honigberg MC
Circ Res 2022 Feb 18;130(4):652-672. Epub 2022 Feb 17 doi: 10.1161/CIRCRESAHA.121.319895. PMID: 35175837Free PMC Article
Subtil SFC, Mendes JMB, Areia ALFA, Moura JPAS
Rev Bras Ginecol Obstet 2020 Dec;42(12):834-840. Epub 2020 Dec 21 doi: 10.1055/s-0040-1721350. PMID: 33348401Free PMC Article
Sculier C, Gaspard N
Seizure 2019 May;68:72-78. Epub 2018 Sep 29 doi: 10.1016/j.seizure.2018.09.018. PMID: 30482654
Tal R, Seifer DB
Am J Obstet Gynecol 2017 Aug;217(2):129-140. Epub 2017 Feb 21 doi: 10.1016/j.ajog.2017.02.027. PMID: 28235465
Hsueh AJ, Kawamura K, Cheng Y, Fauser BC
Endocr Rev 2015 Feb;36(1):1-24. Epub 2014 Sep 9 doi: 10.1210/er.2014-1020. PMID: 25202833Free PMC Article

Therapy

Mohammadian Khonsari N, Khashayar P, Shahrestanaki E, Kelishadi R, Mohammadpoor Nami S, Heidari-Beni M, Esmaeili Abdar Z, Tabatabaei-Malazy O, Qorbani M
Front Endocrinol (Lausanne) 2022;13:857930. Epub 2022 Mar 24 doi: 10.3389/fendo.2022.857930. PMID: 35399938Free PMC Article
Chatzelas DA, Pitoulias AG, Telakis ZC, Kalogirou TE, Tachtsi MD, Christopoulos DC, Pitoulias GA
Int Angiol 2022 Jun;41(3):196-204. Epub 2022 Feb 9 doi: 10.23736/S0392-9590.22.04759-9. PMID: 35138072
Trinder M, Boyd JH, Brunham LR
Curr Opin Lipidol 2019 Apr;30(2):108-116. doi: 10.1097/MOL.0000000000000577. PMID: 30649022
Clayton PE, Hanson D, Magee L, Murray PG, Saunders E, Abu-Amero SN, Moore GE, Black GC
Clin Endocrinol (Oxf) 2012 Sep;77(3):335-42. doi: 10.1111/j.1365-2265.2012.04428.x. PMID: 22624670
Tulandi T, Kinch RA
Obstet Gynecol Surv 1981 Sep;36(9):521-7. doi: 10.1097/00006254-198109000-00026. PMID: 7279334

Prognosis

Kumariya S, Ubba V, Jha RK, Gayen JR
Autophagy 2021 Oct;17(10):2706-2733. Epub 2021 Jun 23 doi: 10.1080/15548627.2021.1938914. PMID: 34161185Free PMC Article
Sculier C, Gaspard N
Seizure 2019 May;68:72-78. Epub 2018 Sep 29 doi: 10.1016/j.seizure.2018.09.018. PMID: 30482654
Tal R, Seifer DB
Am J Obstet Gynecol 2017 Aug;217(2):129-140. Epub 2017 Feb 21 doi: 10.1016/j.ajog.2017.02.027. PMID: 28235465
Geister KA, Camper SA
Annu Rev Genomics Hum Genet 2015;16:199-227. Epub 2015 Apr 22 doi: 10.1146/annurev-genom-090314-045904. PMID: 25939055Free PMC Article
Reusken C, Heyman P
Curr Opin Virol 2013 Feb;3(1):92-9. Epub 2013 Feb 4 doi: 10.1016/j.coviro.2013.01.002. PMID: 23384818

Clinical prediction guides

O'Kelly AC, Michos ED, Shufelt CL, Vermunt JV, Minissian MB, Quesada O, Smith GN, Rich-Edwards JW, Garovic VD, El Khoudary SR, Honigberg MC
Circ Res 2022 Feb 18;130(4):652-672. Epub 2022 Feb 17 doi: 10.1161/CIRCRESAHA.121.319895. PMID: 35175837Free PMC Article
Kumariya S, Ubba V, Jha RK, Gayen JR
Autophagy 2021 Oct;17(10):2706-2733. Epub 2021 Jun 23 doi: 10.1080/15548627.2021.1938914. PMID: 34161185Free PMC Article
Tal R, Seifer DB
Am J Obstet Gynecol 2017 Aug;217(2):129-140. Epub 2017 Feb 21 doi: 10.1016/j.ajog.2017.02.027. PMID: 28235465
Saito S, Kurosawa A, Adachi N
J Hum Genet 2016 Aug;61(8):679-85. Epub 2016 May 12 doi: 10.1038/jhg.2016.46. PMID: 27169690
Geister KA, Camper SA
Annu Rev Genomics Hum Genet 2015;16:199-227. Epub 2015 Apr 22 doi: 10.1146/annurev-genom-090314-045904. PMID: 25939055Free PMC Article

Recent systematic reviews

Formiga F, Baeza LS, Chivite D, Yun S
ESC Heart Fail 2024 Apr;11(2):662-671. Epub 2023 Dec 21 doi: 10.1002/ehf2.14622. PMID: 38130034Free PMC Article
Mohammadian Khonsari N, Khashayar P, Shahrestanaki E, Kelishadi R, Mohammadpoor Nami S, Heidari-Beni M, Esmaeili Abdar Z, Tabatabaei-Malazy O, Qorbani M
Front Endocrinol (Lausanne) 2022;13:857930. Epub 2022 Mar 24 doi: 10.3389/fendo.2022.857930. PMID: 35399938Free PMC Article
Khojah O, Alamoudi S, Aldawsari N, Babgi M, Lary A
Childs Nerv Syst 2021 Dec;37(12):3847-3860. Epub 2021 Aug 3 doi: 10.1007/s00381-021-05284-8. PMID: 34345934Free PMC Article
Monteiro A, Cortez GM, Granja MF, Agnoletto GJ, Kranich J, Padilha MVR, Aldana P, Hanel R
J Neurointerv Surg 2021 Feb;13(2):171-176. Epub 2020 Jun 10 doi: 10.1136/neurintsurg-2020-016069. PMID: 32522788
Kelishadi R, Roufarshbaf M, Soheili S, Payghambarzadeh F, Masjedi M
Child Obes 2017 Aug;13(4):332-346. Epub 2017 Jun 12 doi: 10.1089/chi.2016.0176. PMID: 28604080

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