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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
SNOMED CT: Monocarboxylate transporter 8 deficiency (702327009); Allan-Herndon-Dudley syndrome (702327009); Allan-Herndon syndrome (702327009)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: 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.
 
Gene (location): SLC16A2 (Xq13.2)
 
Monarch Initiative: MONDO:0010354
OMIM®: 300523
Orphanet: ORPHA59

Disease characteristics

Excerpted from the GeneReview: Allan-Herndon-Dudley Syndrome
Allan-Herndon-Dudley syndrome (AHDS), an X-linked disorder, is characterized in males by neurologic findings (hypotonia and feeding difficulties in infancy, developmental delay / intellectual disability ranging from mild to profound) and later-onset pyramidal signs, extrapyramidal findings (dystonia, choreoathetosis, paroxysmal movement disorder, hypokinesia, masked facies), and seizures, often with drug resistance. Additional findings can include dysthyroidism (manifest as poor weight gain, reduced muscle mass, and variable cold intolerance, sweating, elevated heart rate, and irritability) and pathognomonic thyroid test results. Most heterozygous females are not clinically affected but may have minor thyroid test abnormalities. [from GeneReviews]
Authors:
Catherine Sarret  |  Isabelle Oliver Petit  |  Davide Tonduti   view full author information

Additional descriptions

From OMIM
Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. In severe cases, patients never gain the ability to walk or talk (summary by Maranduba et al., 2006).  http://www.omim.org/entry/300523
From MedlinePlus Genetics
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://medlineplus.gov/genetics/condition/allan-herndon-dudley-syndrome

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
Lateral deviation of the great toe (i.e., in the direction of the little 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.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
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).
Prominent antihelix
MedGen UID:
335147
Concept ID:
C1845272
Finding
The presence of an abnormally prominent antihelix.
Stahl ear
MedGen UID:
349571
Concept ID:
C1862689
Congenital Abnormality
The presence of a supernumerary, i.e. third, crus of the helix in the helix, arising at or above the normal bifurcation of the antihelix.
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
Disease or Syndrome
A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
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- or 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 series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
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
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
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
Mental or Behavioral Dysfunction
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
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.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
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 ("pectus") a caved-in ("excavatum") appearance.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
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).
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Elevated circulating thyroid-stimulating hormone concentration
MedGen UID:
108325
Concept ID:
C0586553
Finding
Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation.
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.

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.

Professional guidelines

PubMed

Yiu RS, Ling TK, Ko CH, Poon SW, Poon GW, Wong FC, Law CY, Iwayama H, Lam CW
Clin Chim Acta 2023 Nov 1;551:117621. Epub 2023 Nov 3 doi: 10.1016/j.cca.2023.117621. PMID: 37925810
Krude H, Biebermann H, Schuelke M, Müller TD, Tschöp M
Exp Clin Endocrinol Diabetes 2020 Jun;128(6-07):414-422. Epub 2020 Apr 2 doi: 10.1055/a-1108-1456. PMID: 32242326

Recent clinical studies

Etiology

Freund MET, van der Most F, Visser WE
J Clin Res Pediatr Endocrinol 2024 Mar 11;16(1):1-3. Epub 2024 Feb 12 doi: 10.4274/jcrpe.galenos.2024.2024-1-23. PMID: 38345399Free PMC Article
Solazzi R, Nanni G, Esposito S, Estienne M, Freri E, Zibordi F, Canafoglia L, Castellotti B, Granata T
Pediatr Neurol 2023 Oct;147:24-27. Epub 2023 Jun 22 doi: 10.1016/j.pediatrneurol.2023.06.012. PMID: 37542971
Zucchi R
Thyroid 2020 Aug;30(8):1099-1105. Epub 2020 Apr 7 doi: 10.1089/thy.2020.0071. PMID: 32098589Free PMC Article
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
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

Diagnosis

Becker PC, Güth-Steffens M, Lazarow K, Sonntag N, Braun D, Masfaka I, Renko K, Schomburg L, Köhrle J, von Kries JP, Schweizer U, Krause G, Protze J
Thyroid 2024 Jul;34(7):920-930. Epub 2024 Jul 1 doi: 10.1089/thy.2023.0592. PMID: 38801167
Yiu RS, Ling TK, Ko CH, Poon SW, Poon GW, Wong FC, Law CY, Iwayama H, Lam CW
Clin Chim Acta 2023 Nov 1;551:117621. Epub 2023 Nov 3 doi: 10.1016/j.cca.2023.117621. PMID: 37925810
Guillén-Yunta M, Valcárcel-Hernández V, García-Aldea Á, Soria G, García-Verdugo JM, Montero-Pedrazuela A, Guadaño-Ferraz A
Fluids Barriers CNS 2023 Nov 3;20(1):79. doi: 10.1186/s12987-023-00481-w. PMID: 37924081Free PMC Article
Solazzi R, Nanni G, Esposito S, Estienne M, Freri E, Zibordi F, Canafoglia L, Castellotti B, Granata T
Pediatr Neurol 2023 Oct;147:24-27. Epub 2023 Jun 22 doi: 10.1016/j.pediatrneurol.2023.06.012. PMID: 37542971
Schwartz CE, Stevenson RE
Best Pract Res Clin Endocrinol Metab 2007 Jun;21(2):307-21. doi: 10.1016/j.beem.2007.03.009. PMID: 17574010Free PMC Article

Therapy

Guillén-Yunta M, Valcárcel-Hernández V, García-Aldea Á, Soria G, García-Verdugo JM, Montero-Pedrazuela A, Guadaño-Ferraz A
Fluids Barriers CNS 2023 Nov 3;20(1):79. doi: 10.1186/s12987-023-00481-w. PMID: 37924081Free PMC Article
Giannocco G, Kizys MML, Maciel RM, de Souza JS
Semin Cell Dev Biol 2021 Jun;114:47-56. Epub 2020 Sep 24 doi: 10.1016/j.semcdb.2020.09.007. PMID: 32980238
Krude H, Biebermann H, Schuelke M, Müller TD, Tschöp M
Exp Clin Endocrinol Diabetes 2020 Jun;128(6-07):414-422. Epub 2020 Apr 2 doi: 10.1055/a-1108-1456. PMID: 32242326
Zucchi R
Thyroid 2020 Aug;30(8):1099-1105. Epub 2020 Apr 7 doi: 10.1089/thy.2020.0071. PMID: 32098589Free PMC Article
Groeneweg S, van Geest FS, Peeters RP, Heuer H, Visser WE
Endocr Rev 2020 Apr 1;41(2) doi: 10.1210/endrev/bnz008. PMID: 31754699

Prognosis

Thomas J, Sairoz, Jose A, Poojari VG, Shetty S, K SP, Prabhu R V K, Rao M
Reprod Sci 2023 Jun;30(6):1758-1769. Epub 2023 Jan 3 doi: 10.1007/s43032-022-01162-z. PMID: 36595209Free PMC Article
van Geest FS, Groeneweg S, van den Akker ELT, Bacos I, Barca D, van den Berg SAA, Bertini E, Brunner D, Brunetti-Pierri N, Cappa M, Cappuccio G, Chatterjee K, Chesover AD, Christian P, Coutant R, Craiu D, Crock P, Dewey C, Dica A, Dimitri P, Dubey R, Enderli A, Fairchild J, Gallichan J, Garibaldi LR, George B, Hackenberg A, Heinrich B, Huynh T, Kłosowska A, Lawson-Yuen A, Linder-Lucht M, Lyons G, Monti Lora F, Moran C, Müller KE, Paone L, Paul PG, Polak M, Porta F, Reinauer C, de Rijke YB, Seckold R, Menevşe TS, Simm P, Simon A, Spada M, Stoupa A, Szeifert L, Tonduti D, van Toor H, Turan S, Vanderniet J, de Waart M, van der Wal R, van der Walt A, van Wermeskerken AM, Wierzba J, Zibordi F, Zung A, Peeters RP, Visser WE
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1136-e1147. doi: 10.1210/clinem/dgab750. PMID: 34679181Free PMC Article
Vancamp P, Demeneix BA, Remaud S
Front Endocrinol (Lausanne) 2020;11:283. Epub 2020 May 13 doi: 10.3389/fendo.2020.00283. PMID: 32477268Free PMC Article
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
Verma S
Indian J Pediatr 2008 Apr;75(4):402-4. PMID: 18589880

Clinical prediction guides

Becker PC, Güth-Steffens M, Lazarow K, Sonntag N, Braun D, Masfaka I, Renko K, Schomburg L, Köhrle J, von Kries JP, Schweizer U, Krause G, Protze J
Thyroid 2024 Jul;34(7):920-930. Epub 2024 Jul 1 doi: 10.1089/thy.2023.0592. PMID: 38801167
Guillén-Yunta M, Valcárcel-Hernández V, García-Aldea Á, Soria G, García-Verdugo JM, Montero-Pedrazuela A, Guadaño-Ferraz A
Fluids Barriers CNS 2023 Nov 3;20(1):79. doi: 10.1186/s12987-023-00481-w. PMID: 37924081Free PMC Article
Masnada S, Sarret C, Antonello CE, Fadilah A, Krude H, Mura E, Mordekar S, Nicita F, Olivotto S, Orcesi S, Porta F, Remerand G, Siri B, Wilpert NM, Amir-Yazdani P, Bertini E, Schuelke M, Bernard G, Boespflug-Tanguy O, Tonduti D
Mol Genet Metab 2022 Jan;135(1):109-113. Epub 2021 Dec 16 doi: 10.1016/j.ymgme.2021.12.003. PMID: 34969638
Vancamp P, Demeneix BA, Remaud S
Front Endocrinol (Lausanne) 2020;11:283. Epub 2020 May 13 doi: 10.3389/fendo.2020.00283. PMID: 32477268Free PMC Article
Ramos HE
Endocr Dev 2014;26:108-17. Epub 2014 Aug 29 doi: 10.1159/000363158. PMID: 25231447

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