Format

Send to:

Choose Destination

Links from Books

Allan-Herndon-Dudley syndrome(AHDS)

MedGen UID:
208645
Concept ID:
C0795889
Disease or Syndrome
Synonyms: AHDS; Allan-Herndon syndrome; MCT8 (SLC16A2)-Specific Thyroid Hormone Cell Transporter Deficiency; MCT8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency; Mental retardation and muscular atrophy; Monocarboxylate transporter-8 deficiency; T3 resisitence; T3 RESISTANCE; TRIIODOTHYRONINE RESISTANCE; Triiodothyronine resistence; X-linked mental retardation with hypotonia
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
X-linked recessive inheritance (HPO, OMIM, Orphanet)
X-linked dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Monocarboxylate transporter 8 deficiency (702327009); Allan-Herndon-Dudley syndrome (702327009); Allan-Herndon syndrome (702327009)
 
Gene (location): SLC16A2 (Xq13.2)
OMIM®: 300523
Orphanet: ORPHA59

Definition

MCT8-specific thyroid hormone cell-membrane transporter deficiency is characterized by severe cognitive deficiency, infantile hypotonia, diminished muscle mass and generalized muscle weakness, progressive spastic quadriplegia, joint contractures, and dystonic and/or athetoid movement with characteristic paroxysms or kinesigenic dyskinesias. Seizures occur in about 25% of cases. Most affected males never sit or walk independently or lose these abilities over time; most never speak or have severely dysarthric speech. Brain MRI obtained in the first few years of life shows transient delayed myelination, which improves by age four years. Although psychomotor findings observed in affected males do not occur in heterozygous females, the latter often have thyroid test abnormalities intermediate between affected and normal individuals. [from GTR]

Additional descriptions

From GeneReviews
MCT8-specific thyroid hormone cell-membrane transporter deficiency is characterized by severe cognitive deficiency, infantile hypotonia, diminished muscle mass and generalized muscle weakness, progressive spastic quadriplegia, joint contractures, and dystonic and/or athetoid movement with characteristic paroxysms or kinesigenic dyskinesias. Seizures occur in about 25% of cases. Most affected males never sit or walk independently or lose these abilities over time; most never speak or have severely dysarthric speech. Brain MRI obtained in the first few years of life shows transient delayed myelination, which improves by age four years. Although psychomotor findings observed in affected males do not occur in heterozygous females, the latter often have thyroid test abnormalities intermediate between affected and normal individuals.  https://www.ncbi.nlm.nih.gov/books/NBK26373
From GHR
Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.Most children with Allan-Herndon-Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood.  https://ghr.nlm.nih.gov/condition/allan-herndon-dudley-syndrome

Clinical features

Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.
Thyroid-stimulating hormone excess
MedGen UID:
108325
Concept ID:
C0586553
Finding
Overproduction of thyroid-stimulating hormone (TSH) by the anterior pituitary gland.
Rotary nystagmus
MedGen UID:
116106
Concept ID:
C0240595
Disease or Syndrome
A form of nystagmus in which the eyeball makes rotary motions around the axis.
Abnormal conjugate eye movement
MedGen UID:
337198
Concept ID:
C1845274
Finding
Any deviation from the normal motor coordination of the eyes that allows for bilateral fixation on a single object.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot anomaly in which one or more of the arches of the foot have flattened out.
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
A deformity characterized by lateral deviation of the great toe.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Stahl ear
MedGen UID:
609005
Concept ID:
C0431480
The presence of a supernumerary, i.e. third, crus of the helix (FMA:61024) in the helix, arising at or above the normal bifurcation of the antihelix.
Prominent antihelix
MedGen UID:
335147
Concept ID:
C1845272
Finding
The presence of an abnormally prominent antihelix.
Macrotia
MedGen UID:
349900
Concept ID:
C1860838
Finding
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Underfolded superior helices
MedGen UID:
870218
Concept ID:
C4024655
Anatomical Abnormality
A condition in which the superior portion of the helix is folded over to a lesser degree than normal.
Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Sign or Symptom
A dyskinesia characterized by an inability to maintain the fingers, toes, tongue, or other body parts in a stable position, resulting in continuous slow, sinusoidal, and flowing involuntary movements. This condition is frequently accompanied by CHOREA, where it is referred to as choreoathetosis. Athetosis may occur as a manifestation of BASAL GANGLIA DISEASES or DRUG TOXICITY. (From Adams et al., Principles of Neurology, 6th ed, p76)
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A form of involuntary muscular movement characterized by alternating contractions and relaxation in rapid succession. In the context of reflex testing, the ability to elicit clonus indicates injury to the nerve tracts above the point at which the reflex was initiated.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Excessive production of saliva.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from CRANIAL NERVE DISEASES; NEUROMUSCULAR DISEASES; CEREBELLAR DISEASES; BASAL GANGLIA DISEASES; BRAIN STEM diseases; or diseases of the corticobulbar tracts (see PYRAMIDAL TRACTS). The cortical language centers are intact in this condition. (From Adams et al., Principles of Neurology, 6th ed, p489)
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
A group of rare genetic neurodegenerative disorders that affect infants and children. These disorders are characterized by metabolic abnormalities in the development of the myelin sheaths in the white matter. Clinical signs and symptoms include developmental delays, mental retardation, dementia, seizures, loss of motor skills, and muscle weakness. Representative examples include metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
A reflex characterized by upward movement of the great toe and an outward movement of the rest of the toes, when the sole of the foot is stroked. It is a normal reflex up to the age of two. Its presence beyond that age indicates neurological damage.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Autonomic nervous system overreaction to stimuli, most commonly after spinal cord injury at a T-5 level and above.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
A type of spastic cerebral palsy characterized by increased muscle tone of all four extremities.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
A response indicating that an individual is or was unable to walk.
Thyroid-stimulating hormone excess
MedGen UID:
108325
Concept ID:
C0586553
Finding
Overproduction of thyroid-stimulating hormone (TSH) by the anterior pituitary gland.
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.
Intellectual disability, progressive
MedGen UID:
337397
Concept ID:
C1846149
Finding
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
Feelings of annoyance, impatience, and anger.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
A type of spastic cerebral palsy characterized by increased muscle tone of all four extremities.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
A deformity characterized by lateral deviation of the great toe.
Scoliosis
MedGen UID:
21278
Concept ID:
C0037932
Finding
Deformities of the SPINE characterized by abnormal bending or flexure in the vertebral column. They may be bending forward (KYPHOSIS), backward (LORDOSIS), or sideway (SCOLIOSIS).
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest (\
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Excessive production of saliva.
Microcephaly
MedGen UID:
473122
Concept ID:
C0424688
Finding
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
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).
Flexion contracture
MedGen UID:
3227
Concept ID:
C0009917
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.
Thyroid-stimulating hormone excess
MedGen UID:
108325
Concept ID:
C0586553
Finding
Overproduction of thyroid-stimulating hormone (TSH) by the anterior pituitary gland.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAllan-Herndon-Dudley syndrome
Follow this link to review classifications for Allan-Herndon-Dudley syndrome in Orphanet.

Recent clinical studies

Etiology

Kim JH, Kim YM, Yum MS, Choi JH, Lee BH, Kim GH, Yoo HW
Horm Res Paediatr 2015;83(4):288-92. Epub 2015 Apr 15 doi: 10.1159/000371466. PMID: 25896225
La Piana R, Vanasse M, Brais B, Bernard G
J Child Neurol 2015 Sep;30(10):1371-4. Epub 2014 Nov 7 doi: 10.1177/0883073814555189. PMID: 25380603
Kobayashi S, Onuma A, Inui T, Wakusawa K, Tanaka S, Shimojima K, Yamamoto T, Haginoya K
Pediatr Neurol 2014 Sep;51(3):414-6. Epub 2014 May 9 doi: 10.1016/j.pediatrneurol.2014.05.004. PMID: 25160547
Kersseboom S, Kremers GJ, Friesema EC, Visser WE, Klootwijk W, Peeters RP, Visser TJ
Mol Endocrinol 2013 May;27(5):801-13. Epub 2013 Apr 2 doi: 10.1210/me.2012-1356. PMID: 23550058Free PMC Article
Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE
Am J Hum Genet 2005 Jul;77(1):41-53. Epub 2005 May 11 doi: 10.1086/431313. PMID: 15889350Free PMC Article

Diagnosis

Kim JH, Kim YM, Yum MS, Choi JH, Lee BH, Kim GH, Yoo HW
Horm Res Paediatr 2015;83(4):288-92. Epub 2015 Apr 15 doi: 10.1159/000371466. PMID: 25896225
Langley KG, Trau S, Bean LJ, Narravula A, Schrier Vergano SA
Am J Med Genet A 2015 May;167A(5):1117-20. Epub 2015 Mar 8 doi: 10.1002/ajmg.a.36970. PMID: 25755011
Azzolini S, Nosadini M, Balzarin M, Sartori S, Suppiej A, Mardari R, Greggio NA, Toldo I
Brain Dev 2014 Sep;36(8):716-20. Epub 2013 Nov 19 doi: 10.1016/j.braindev.2013.10.009. PMID: 24268987
Boccone L, Dessì V, Meloni A, Loudianos G
Eur J Med Genet 2013 Apr;56(4):207-10. Epub 2013 Feb 16 doi: 10.1016/j.ejmg.2013.02.001. PMID: 23419639
Verma S
Indian J Pediatr 2008 Apr;75(4):402-4. PMID: 18589880

Therapy

Braun D, Schweizer U
Endocrinology 2017 Mar 1;158(3):678-691. doi: 10.1210/en.2016-1530. PMID: 27977298
Ferrara AM, Liao XH, Ye H, Weiss RE, Dumitrescu AM, Refetoff S
Endocrinology 2015 Nov;156(11):3889-94. Epub 2015 Aug 31 doi: 10.1210/en.2015-1234. PMID: 26322373Free PMC Article
Krude H, Kühnen P, Biebermann H
Best Pract Res Clin Endocrinol Metab 2015 Jun;29(3):399-413. Epub 2015 Apr 26 doi: 10.1016/j.beem.2015.04.004. PMID: 26051299
Kersseboom S, Horn S, Visser WE, Chen J, Friesema EC, Vaurs-Barrière C, Peeters RP, Heuer H, Visser TJ
Mol Endocrinol 2014 Dec;28(12):1961-70. doi: 10.1210/me.2014-1135. PMID: 25389909Free PMC Article
Zung A, Visser TJ, Uitterlinden AG, Rivadeneira F, Friesema EC
Eur J Endocrinol 2011 Nov;165(5):823-30. Epub 2011 Sep 6 doi: 10.1530/EJE-11-0358. PMID: 21896621

Prognosis

Groeneweg S, Lima de Souza EC, Meima ME, Peeters RP, Visser WE, Visser TJ
Endocrinology 2017 Oct 1;158(10):3292-3306. doi: 10.1210/en.2017-00082. PMID: 28977587
Matheus MG, Lehman RK, Bonilha L, Holden KR
J Child Neurol 2015 Oct;30(12):1664-8. Epub 2015 Apr 21 doi: 10.1177/0883073815578524. PMID: 25900139
La Piana R, Vanasse M, Brais B, Bernard G
J Child Neurol 2015 Sep;30(10):1371-4. Epub 2014 Nov 7 doi: 10.1177/0883073814555189. PMID: 25380603
Kobayashi S, Onuma A, Inui T, Wakusawa K, Tanaka S, Shimojima K, Yamamoto T, Haginoya K
Pediatr Neurol 2014 Sep;51(3):414-6. Epub 2014 May 9 doi: 10.1016/j.pediatrneurol.2014.05.004. PMID: 25160547
Verma S
Indian J Pediatr 2008 Apr;75(4):402-4. PMID: 18589880

Clinical prediction guides

Groeneweg S, Lima de Souza EC, Meima ME, Peeters RP, Visser WE, Visser TJ
Endocrinology 2017 Oct 1;158(10):3292-3306. doi: 10.1210/en.2017-00082. PMID: 28977587
Armour CM, Kersseboom S, Yoon G, Visser TJ
PLoS One 2015;10(10):e0139343. Epub 2015 Oct 1 doi: 10.1371/journal.pone.0139343. PMID: 26426690Free PMC Article
Matheus MG, Lehman RK, Bonilha L, Holden KR
J Child Neurol 2015 Oct;30(12):1664-8. Epub 2015 Apr 21 doi: 10.1177/0883073815578524. PMID: 25900139
Wirth EK, Roth S, Blechschmidt C, Hölter SM, Becker L, Racz I, Zimmer A, Klopstock T, Gailus-Durner V, Fuchs H, Wurst W, Naumann T, Bräuer A, de Angelis MH, Köhrle J, Grüters A, Schweizer U
J Neurosci 2009 Jul 29;29(30):9439-49. doi: 10.1523/JNEUROSCI.6055-08.2009. PMID: 19641107
Frints SG, Lenzner S, Bauters M, Jensen LR, Van Esch H, des Portes V, Moog U, Macville MV, van Roozendaal K, Schrander-Stumpel CT, Tzschach A, Marynen P, Fryns JP, Hamel B, van Bokhoven H, Chelly J, Beldjord C, Turner G, Gecz J, Moraine C, Raynaud M, Ropers HH, Froyen G, Kuss AW
Eur J Hum Genet 2008 Sep;16(9):1029-37. Epub 2008 Apr 9 doi: 10.1038/ejhg.2008.66. PMID: 18398436

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center