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Genetic, Metabolic and Mitochondrial Disorders

This page includes links to information about genetic, metabolic or mitochondrial disorders which are known to affect the intelligibility of speech and/or speech development. Some of these conditions specifically are associated with childhood apraxia of speech.  In a 2013 study, researchers determined that Whole Exome Sequencing (WES) was helpful in identifying genetic differences in a group of children with childhood apraxia of speech.  The authors write:

“Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent.” (Worthy et. al., 2013)

7q11.23 Duplication syndrome
7q11.23 duplication syndrome is a developmental disorder resulting from an extra copy of ~25 genes on the long arm of chromosome 7. Individuals who have 7q11.23 duplication syndrome have 3 copies of the genes in this region. Characteristics associated with “dup7” include: significant expressive speech and language delays, ranging from mildly affected to children with a diagnosis of apraxia of speech, receptive language often stronger than expressive, behavioral concerns such as social phobias and separation anxiety (possibly secondary to limited speech), possible oppositional defiance disorder; sometimes misdiagnosed as on autism spectrum.

7q31 (FOXP2) – the FOXP2 gene is the first one that was associated with the development of speech and was first found in a multigenerational family in which 1/2 of its members had apraxia of speech and other associated conditions

Angelman Syndrome
Developmental delay, functionally severe; speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones; Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs; Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span.

Cohen Syndrome
Malformations of the head and facial (craniofacial) area, eye (ocular) abnormalities, diminished muscle tone (hypotonia), obesity, abnormally narrow hands and feet with long fingers and toes, and/or mental retardation. In infants and children with the disorder, characteristic craniofacial malformations may include an unusually small head (microcephaly); abnormal shortness of the groove in the middle of the upper lip (philtrum); a small jaw (micrognathia); an unusually narrow, highly-arched roof of the mouth (palate); prominent front teeth (incisors); a high nasal bridge; downslanting eyelid folds (palpebral fissures); and/or malformed, protruding ears.

CDGS – Congenital Disorders of Glycosylation
“abnormal synthesis of sugar groups that are parts of glycoproteins (“sugarproteins”). The current identified types of CDG are Type 1a, 1b, 1c, 1d, 1e and IIa. Many children with CDG have serious life threatening medical problems during their infancy. Children and adults with CDG type 1a have varying degrees of disabilities including cognitive impairment, speech difficulties, poor balance and motor skills, some walk with support, many are in wheelchairs.”-CDG Family Network.

Cornelia deLange Syndrome
Typical facial features include thin eyebrows that meet in the middle, long eyelashes, a short upturned nose, and thin downturned lips. Other characteristics include low birth weight (often under five pounds), slow growth, small stature, and small head size. Other features may include excessive body hair and small hands and feet. Common medical issues include gastro- esophageal reflux disease, heart defects, seizures, feeding difficulties, vision problems, and hearing loss. Limb differences, including missing arms, forearms or fingers, are seen in about 25 percent of individuals with CdLS. Behavioral and communication issues and developmental delays often exist.

Ectodermal Dysplasias
There are many types of Ectodermal Dysplasias, some of which may be associated with speech delay. The ectodermal dysplasias are inherited disorders that involve defects in the hair, nails, sweat glands and teeth. When a person has at least two types of abnormal ectodermal features—for example, malformed teeth and extremely sparse hair—the individual is identified as being affected by ectodermal dysplasia.
The conditions are a diverse group of disorders which may also affect other parts of the body. The ectoderm contributes to the formation of the lens of the eye, parts of the inner ear, the fingers and toes, and nerves, among others. Therefore, ectodermal dysplasia may cause these parts of the body to develop abnormally. There are more than 150 different types of ectodermal dysplasias. Very few types involve learning difficulties.

Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of heritable connective tissue disorders characterized by articular hypermobility, skin extensibility, low muscle tone, and tissue fragility.

Fragile X Speech and Language Therapy
Children with fragile X syndrome have unique speech and language disorders. Boys with fragile X often have particular problems with pragmatics (conversational skills). Their speech and language are affected by physical, oral-motor, attention, and behavioral characteristics, such that an integrated approach to treatment is necessary.

Galactosemia means too much galactose in the blood caused by the individual “missing” the enzyme (known as GALT) to convert galactose into glucose. ..Although galactosemic children are started on diet restriction at birth, there continues to be a high incidence of long-term complications involving speech and language, fine and gross motor skill delays and specific learning disabilities. A subset of children with Galactosemia have childhood apraxia of speech.

Symptoms associated with Homocystinuria may include mental retardation, seizures, psychiatric disturbances, delays in reaching developmental milestones (e.g., crawling, walking, sitting), displacement of the lens of the eye (ectopia lentis), abnormal thinning and weakness of the bones (osteoporosis and scoliosis ), and/or the formation of blood clots (thrombi) in various veins and arteries that may lead to life-threatening complications.

Hypomelanosis of Ito
Hypomelanosis of Ito (HI) is a syndrome with hypopigmented whorls of skin along the Blaschko lines. Can involve seizures, developmental delays, tooth or mouth problems.

Joubert Syndrome
Individuals diagnosed with Joubert syndrome have an absence or underdevelopment of part of the brain called the cerebellar vermis which controls balance and coordination. The severity of the resulting ataxia (uncoordinated movements) varies from person to person. Decreased muscle tone is common in children with Joubert syndrome. As a result of the poor muscle tone, developmental delay (usually in gross motor, fine motor and speech areas) is common. Some children have also been noted to have abnormal eye and tongue movements.

Kabuki Syndrome
Characteristics include facial features such as arched eyebrows with sparseness in the outer half, misshapen or prominent ears, depressed nasal tip; skeletal abnormalities of the fingers or vertebrae; persistent finger fetal pads, mild to moderate intellectual disability; and short stature. Over 70% of cases can be caused by mutation of the MLL2 gene. These children have speech characteristics such as resonance & prosody differences and articulation challenges, some which may be similar or characterized as apraxia of speech.

Klinefelter’s syndrome (also XXY)

Koolen de Vries syndrome (17q21.31 microdeletion)
Speech of children with this disorder has recently been characterized and includes apraxia, dysarthria, and stuttering.  Other developmental concerns are also present.

Landau-Kleffner Syndrome

Marinesco-Sjogren Syndrome

Mitochondrial Disease Descriptions

Neurofibromitosis 1
Neurofibromas, the most common tumors in NF, are benign growths which typically develop on or just underneath the surface of the skin but may also occur in deeper areas of the body. Neurofibromas, which are composed of tissue from the nervous system (neuro) and fibrous tissue (fibroma), usually develop around puberty although they may appear at any age. Café-au-lait spots, the most common sign of NF, are the flat, pigmented spots on the skin, which are called by the French term for coffee (café) with milk (lait) because of their light tan color. People with NF almost always have six or more café-au-lait spots. A significant number of children with NF1 have speech delay or disorders.

Neurotransmitter Diseases

Opitz G/BBB Syndrome

Phelan McDermid Syndrome (22q13 deletion syndrome)

Prader-Willi Syndrome

Rett Syndrome

Rubinstein-Taybi Syndrome
The only way to know if someone has the condition is by noting the characteristic physical features. The facial features include a small head size, thick scalp hair which may extend onto the forehead, down-slanting eyes, prominent nose, small mouth, and a high-arched palate. Additionally, the thumbs and first toes are broad and sometimes angulated….Speech problems are present in about 90% of patients.

Smith-Lemli-Opitz Syndrome

Smith-Magenis Syndrome (SMS)

Sotos Syndrome

Terminal 22q deletion syndrome
Symptoms include severe speech delay or absent speech; low muscle tone; possible motor skill regression; possible features of autism; atypical facial features

Triplo-x Syndrome
Affects only girls. Females with Triplo-x have an extra X chromosomes in the cells of their body. Speech and language delays common.

Trisomy 9p

Tuberous Sclerosis

Velocardiofacial Syndrome (VCF)
(also called Shprintzen Syndrome, DiGeorge Sequence and, 22q11.2 deletion)

Worster Drought Syndrome