Allan-Herndon-Dudley syndrome (AHDS)

What is Allan-Herndon-Dudley syndrome (AHDS)?

This rare disease is a genetic inherited condition that affects mainly males, due to the way in which it is inherited.

It primarily affects brain development and in turn intellectual ability. Limited to zero speech development is also a defining feature of this syndrome.

This syndrome is also known as:
AHDS Allan-herndon Syndrome; Mental Retardation And Muscular Atrophy Mental Retardation, X-linked, With Hypotonia Monocarboxylate Transporter 8 Deficiency T3 Resistance, Triiodothyronine Resistance

What gene changes cause Allan-Herndon-Dudley syndrome (AHDS)?

The syndrome is an X-linked recessive condition. Mutations in the SLC16A2 are responsible for the condition.

Syndromes inherited in an X-linked recessive pattern generally only affect males. Males only have one X chromosome, and so one copy of a gene mutation on it causes the syndrome. Females, with two X chromosomes, only one of which will be mutated, are not likely to be affected.

What are the main symptoms of Allan-Herndon-Dudley syndrome (AHDS)?

Moderate to severe intellectual disability is a major symptom of the syndrome. This includes the development of zero to limited speech.

Other major symptoms include hypotonia, weakness in the muscles related to under developed muscles, muscle stiffness and involuntary movements. This affects an individual's ability to move and walk, and by adulthood most individuals with the condition are wheelchair bound. It may also cause bowel and urinary incontinence.

Facial features of the condition include a narrow face, large ears and underdeveloped cheekbones.

Possible clinical traits/features:
Stahl ear, Type I diabetes mellitus, Microcephaly, Severe global developmental delay, Scoliosis, Spastic tetraplegia, X-linked dominant inheritance, Spastic paraplegia, Rotary nystagmus, Congenital onset, Ptosis, Proptosis, Camptodactyly of finger, Upslanted palpebral fissure, Delayed CNS myelination, Limitation of joint mobility, Abnormal conjugate eye movement, Clonus, Drooling, Dysarthria, Feeding difficulties in infancy, Flexion contracture, Pes planus, Prominent antihelix, Open mouth, Single transverse palmar crease, Skeletal muscle atrophy, Cerebral calcification, Ataxia, Abnormality of the neck, Abnormality of the rib cage, Babinski sign, Neurological speech impairment, Neonatal hypotonia, Narrow forehead, Intellectual disability, progressive, Intellectual disability, severe, Involuntary writhing movements, Narrow face, Pectus excavatum, Leukodystrophy, Macrotia, Irritability, Increased thyroid-stimulating hormone level, Hypothyroidism, Incoordination, Inability to walk

How does someone get tested for Allan-Herndon-Dudley syndrome (AHDS)?

The initial testing for Allan-Herndon-Dudley syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Medical information on Allan-Herndon-Dudley syndrome (AHDS)

A large X-linked kindred, first ascertained by Allan et al., (1944) was re-studied by Stevenson et al., (1990). Linkage was established to Xq21. Affected males had severe mental retardation, dysarthria, ataxia, athetoid movements, muscle hypoplasia, and spastic paraplegia with hyperreflexia. The facies were elongated and characterised by bitemporal narrowing, a normal head circumference, large, simple or cup-shaped ears. Neck drop was a frequent sign (limber neck), apparently caused by weakening of the neck muscles. The authors suggested that the family briefly described by Davis et al., (1981) may have had the same condition. Bialer et al., (1992) studied this family in more detail and established the clinical similarities and mapping to Xq21. They pointed out that Wieacker-Wolff syndrome (qv) has similarities, but mental retardation is less severe and there is no spasticity in that condition. The family reported by Ulku et al., (1992) is difficult to classify because of limited clinical detail, but it may also fall into this group. Although the majority of cases have delayed myelination, this is not always the case (Azzoliniu et al., 2014). However, Yamamoto et al., 2015) suggest that this might be delayed mtelination.
Dumitrescu et al., (2004) and Friesema et al., (2004) described mutations in a monocarboxylate transporter gene MCT8 needed for triiodothyronine transport into neurons. Schwartz et al., (2005) provide an excellent, overview of the entity. Some have a myopathic facies, but in general the face is not distinctive. Drooling is often constant. With the passage of time, hypotonia is replaced by spasticity and the hands develop a dystonic posture.Not all patients have abnormal serum T3 levels (Boccone et al., 2013)
Passos-Bueno et al., (1993) reported a family with a form of X-linked mental retardation that also mapped to Xp11. This seemed to be associated with muscle atrophy and the patients were never able to hold their head against gravity, to sit unsupported, or to walk or speak. There were some similarities to Allan-Herndon syndrome. This family was re-evaluated by Zorick et al., (2004) and Maranduba et al., (2006) and mutations were found in MCT8. All obligate female carriers were mentally, normal. There was a deficient cellular uptake of T3. Elevated serum T3 levels might be a useful marker in mentally handicapped males (Frints et al., 2008). These authors also reported a female with the full-blown picture who had a t(X;9)(q13.2;p24) de novo translocation and non-random X-inactivation.
The family (with a SLC16A2 mutation), reported by Gika et al., (2010), had paroxysmal chorea-athetosis, dystonia, hypotonia and hypothyroidism, and one had delayed myelination and was initially thought to have Pelizaeus-Merzbacher disease. Others had been diagnosed with dystonic CP. One had a myopathic face. The patient reported by Yamanoto et al., (2013) with a SLC16A2 mutation had high T3 levels. T3 levels were also diagnostically useful in the family reported by Langley et al., (2015).

* This information is courtesy of the L M D.

If you find a mistake or would like to contribute additional information, please email us at: [email protected]

Get Faster and More Accurate Genetic Diagnosis!

More than 250,000 patients successfully analyzed!
Don't wait years for a diagnosis. Act now and save valuable time.

Start Here!

"Our road to a rare disease diagnosis was a 5-year journey that I can only describe as trying to take a road trip with no map. We didn’t know our starting point. We didn’t know our destination. Now we have hope."

Image

Paula and Bobby
Parents of Lillie

What is FDNA Telehealth?

FDNA Telehealth is a leading digital health company that provides faster access to accurate genetic analysis.

With a hospital technology recommended by leading geneticists, our unique platform connects patients with genetic experts to answer their most pressing questions and clarify any concerns they may have about their symptoms.

Benefits of FDNA Telehealth

FDNA icon

Credibility

Our platform is currently used by over 70% of geneticists and has been used to diagnose over 250,000 patients worldwide.

FDNA icon

Accessibility

FDNA Telehealth provides facial analysis and screening in minutes, followed by fast access to genetic counselors and geneticists.

FDNA icon

Ease of Use

Our seamless process begins with an initial online diagnosis by a genetic counselor and follows by consultations with geneticists and genetic testing.

FDNA icon

Accuracy & Precision

Advanced artificial intelligence (AI) capabilities and technology with a 90% accuracy rate for a more accurate genetic analysis.

FDNA icon

Value for
Money

Faster access to genetic counselors, geneticists, genetic testing, and a diagnosis. As fast as within 24 hours if required. Save time and money.

FDNA icon

Privacy & Security

We guarantee the utmost protection of all images and patient information. Your data is always safe, secure, and encrypted.

FDNA Telehealth can bring you closer to a diagnosis.
Schedule an online genetic counseling meeting within 72 hours!