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Allan-Herndon-Dudley Syndrome

Congenital hypothyroidism


Presentation

  • The c.1A T change in another patient affects a putative translation start codon, but the same change was present in his healthy brother.[ncbi.nlm.nih.gov]
  • Affected males also present with muscle hypoplasia, generalized muscle weakness, and limited speech.[ncbi.nlm.nih.gov]
  • The c.1834delC segregates with the disease in this family and it was not present in 100 control chromosomes, further confirming its pathogenicity.[ncbi.nlm.nih.gov]
  • Hypotonia and severe intellectual deficit are present in 100% of patients. Severe psychomotor delay is present from the outset (delay of motor and language milestones) and autonomy is never reached.[orpha.net]
  • All affected siblings presented with classic findings of Allan-Herndon-Dudley syndrome, and each of the siblings also developed intermittent esotropia.[ncbi.nlm.nih.gov]
Nightmare
  • Be sure that if you were to compare fairly, your best day would probably be anyone’s worst nightmare. You have a complicated and hard life. This is why, comparing others’ problems with your own is never helpful.[themighty.com]
Large Ears
  • Characteristics included severe mental retardation, spastic paraplegia, dysarthria, muscle wasting, scoliosis, broad shallow pectus excavatum, long face, large ears with minor modeling anomalies, foot deformities, joint contractures, and neck drop.[ncbi.nlm.nih.gov]
  • Two of them displayed long face, narrow forehead and cheeks, opened mouth, thick lips, tented upper lips and large ears ( Fig. 1 ). There was no significant regression during the course of the disease in our patients.[content.iospress.com]
Esotropia
  • All affected siblings presented with classic findings of Allan-Herndon-Dudley syndrome, and each of the siblings also developed intermittent esotropia.[ncbi.nlm.nih.gov]
Severe Mental Retardation
  • Abstract We report a novel 1 bp deletion (c.1834delC) in the MCT8 gene in a large Brazilian family with Allan-Herndon-Dudley syndrome (AHDS), an X linked condition characterised by severe mental retardation and neurological dysfunction.[ncbi.nlm.nih.gov]
  • This syndrome is characterized by axial hypotonia, severe mental retardation, dysarthria, athetoid movements, spastic paraplegia, and a typical thyroid hormone profile.[ncbi.nlm.nih.gov]
  • Recently mutations in the SLC16A2 gene coding for the monocarboxylate thyroid hormone transporter 8, MCT8, have been associated with Allan-Herndon-Dudley syndrome (AHDS), an X-linked condition characterized by severe mental retardation, dysarthria, athetoid[ncbi.nlm.nih.gov]
  • Characteristics included severe mental retardation, spastic paraplegia, dysarthria, muscle wasting, scoliosis, broad shallow pectus excavatum, long face, large ears with minor modeling anomalies, foot deformities, joint contractures, and neck drop.[ncbi.nlm.nih.gov]
  • Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) prevent appropriate entry of thyroid hormones into brain cells during development and cause severe mental retardation in affected patients.[ncbi.nlm.nih.gov]
Large Anterior Fontanels
  • This patient had a classic AHDS phenotype with an unexpectedly large anterior fontanel and delayed bone age and dentition.[ncbi.nlm.nih.gov]
Spastic Paraplegia
  • Allan-Herndon-Dudley syndrome (AHDS), an X linked condition, is characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia in combination with altered TH levels, in particular, high serum[ncbi.nlm.nih.gov]
  • Allan-Herndon-Dudley syndrome (AHDS, MIM 300523) is an X-linked neurodegenerative disorder characterized by intellectual disability, severe hypotonia, diminished muscle mass, and progressive spastic paraplegia.[ncbi.nlm.nih.gov]
  • Allan-Herndon-Dudley syndrome, an X-linked condition characterized by severe intellectual disability, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia, is associated with defects in the monocarboxylate transporter 8 gene (MCT8[ncbi.nlm.nih.gov]
  • Typical features include severe cognitive impairment, truncal hypotonia, spastic paraplegia, weakness, and speech difficulties. Minimal literature exists describing the ocular findings in patients with Allan-Herndon-Dudley syndrome.[ncbi.nlm.nih.gov]
  • We identified 2 AHDS patients with developmental delays, truncal hypotonia, and spastic paraplegia. These patients presented with psychomotor retardation and characteristic thyroid function abnormalities, such as elevated T3 and low T4 levels.[ncbi.nlm.nih.gov]
Confusion
  • Whether your child’s application is being reviewed for eligibility under SSI or SSDI, the application and review processes can be confusing.[disabilitybenefitscenter.org]
  • I was confused and quite pissed but I forgave them instantly when I felt mom’s touch as she kissed me on my forehead. Overall that was one traumatizing day but a new beginning none the less. Things went well for the first three months.[rarediseaseday.org]
Opisthotonus
  • He showed hypertonus of his extremities and often displayed an asymmetrical tonic neck reflex posture with opisthotonus. He could neither turn over nor sit.[nature.com]

Workup

Excessive Drooling
  • Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to ambulate independently, or ataxia in those who do ambulate. Speech is dysarthric or absent altogether.[ncbi.nlm.nih.gov]
  • Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to walk independently, or ataxia in those who do walk. Speech is dysarthric or absent altogether.[egl-eurofins.com]

Treatment

  • Iodothyronines in CSF are low irrespective of treatment, suggesting blood-CSF barrier transport of T3-T4 is restricted in AHDS.[hdl.handle.net]
  • Although the clinical features of hypothyroidism cannot be improved by only administering levothyroxine treatment, early diagnosis, management, and appropriate genetic counseling should be provided to at-risk families.[ncbi.nlm.nih.gov]
  • In May 2013, the US FDA granted Orphan drug status to Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency.[en.wikipedia.org]

Prognosis

  • The long-term prognosis of Allan-Herndon-Dudley syndrome remains uncertain. We describe the clinical features and course of four adults in a family with Allan-Herndon-Dudley syndrome with athetoid type cerebral palsy.[ncbi.nlm.nih.gov]
  • The long-term prognosis of Allan-Herndon-Dudley syndrome remains uncertain. PATIENTS: We describe the clinical features and course of four adults in a family with Allan-Herndon-Dudley syndrome with athetoid type cerebral palsy.[mct8.info]
  • Prognosis Although several patients have survived into their 60s, overall life expectancy is compromised and quality of life is severely affected as most patients are unable to sit, stand or walk independently.[orpha.net]
  • Diagnosis - Bamforth syndrome Prognosis - Bamforth syndrome Prognosis is good with proper treatment and children can have normal growth and development. Treatment - Bamforth syndrome Not supplied. Resources - Bamforth syndrome[checkorphan.org]
  • Prognosis With proper treatment adherence the prognosis is good and children can have normal physical growth, pubertal development, and anterior pituitary function.[rarediseases.info.nih.gov]

Etiology

  • 2. secondary/central hypothyroidism 3. peripheral hypothyroidism Also, 1. permanent CH 2. transient CH Etiology of secondary/central hypothyroidism deficiency of thyroid stimulating hormone Etiology of peripheral hypothyroidism defects of thyroid hormone[quizlet.com]
  • Although the prevalence is unknown, one study identified AHDS in 1.4% of males with intellectual disability of unknown etiology. Only males are affected.[orpha.net]
  • CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies.[sprout038.sprout.yale.edu]
  • "Perspective: genetic defects in the etiology of congenital hypothyroidism". Endocrinology . 143 (6): 2019–24. doi : 10.1210/en.143.6.2019 . PMID 12021164 . Venza I, Visalli M, Parrillo L, De Felice M, Teti D, Venza M (March 2011).[en.wikipedia.org]

Epidemiology

  • Summary Epidemiology At least 132 families with 320 affected individuals have been reported in the literature to date. Although the prevalence is unknown, one study identified AHDS in 1.4% of males with intellectual disability of unknown etiology.[orpha.net]
  • Epidemiology Only 8 patients from 6 families have been reported to date.[rarediseases.info.nih.gov]
  • […] children with simple obesity in relation to body mass index‏ EA Abdel-Aziz, RT Hamza, AM Youssef, FM Mohammed ‏ Egyptian Journal of Medical Human Genetics 15 (2), 149-154 , 2014 ‏ 17 2014 Penile length and genital anomalies in Egyptian male newborns: epidemiology[scholar.google.com.eg]
Sex distribution
Age distribution

Pathophysiology

  • Mol Endocrinol 25 : 1 – 14 8. 2009 Minireview: pathophysiological importance of thyroid hormone transporters. Endocrinology 150 : 1078 – 1083 9. 2006 Tissue specific thyroid hormone deprivation and excess in Mct8 deficient mice.[doi.org]

Prevention

  • Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) prevent appropriate entry of thyroid hormones into brain cells during development and cause severe mental retardation in affected patients.[ncbi.nlm.nih.gov]
  • Prevention of secondary complications: Braces to prevent joint contractures and orthopedic surgery, if necessary. Dietary restrictions to prevent aspiration.[ncbi.nlm.nih.gov]
  • Prevention - Bamforth syndrome Not supplied. Diagnosis - Bamforth syndrome Prognosis - Bamforth syndrome Prognosis is good with proper treatment and children can have normal growth and development. Treatment - Bamforth syndrome Not supplied.[checkorphan.org]
  • Currently, Bamforth-Lazarus Syndrome may not be preventable, since it is a genetic disorder.[dovemed.com]
  • […] accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 October 2017 recommending the granting of this designation. the seriousness of the condition; the existence of alternative methods of diagnosis, prevention[ema.europa.eu]

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