Ohdo syndrome, SBBYS Variant (SBBYSS)

What is Ohdo syndrome, SBBYS Variant (SBBYSS)?

This is a rare disease is a genetic condition that affects multiple parts of the body. Severe intellectual disability is a major syndrome.

To date, there are 19 recorded cases of the syndrome worldwide and it is thought to occur in more than 1 in 1 million live births worldwide.

Syndrome Synonyms:
Mental Retardation, Congenital Heart Disease, Blepharophimosis, Blepharoptosis, And Hypoplastic Teeth Ohdo Blepharophimosis Syndrome Say-barber-biesecker-young-simpson Syndrome Young-simpson Syndrome; Yss

What gene changes cause Ohdo syndrome, SBBYS Variant (SBBYSS)?

Changes in the KAT6 gene are responsible for the syndrome. The majority of diagnosed cases so far have been de novo mutations.

In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation which occurs during the reproductive process.

What are the main symptoms of Ohdo syndrome, SBBYS Variant (SBBYSS)?

A major symptom of the syndrome is severe intellectual disability, as well as limited to zero speech development.

Unique physical and facial characteristics of the syndrome include underdeveloped eyelids that cover part of the eye, a mask like, immobile face, a small mouth, small pointed teeth, thin upper lip, a large nasal tip, large toes and very long thumbs. A cleft palate occurs in 1/3 of all individuals with the syndrome.

Missing knee caps, or underdeveloped knee caps are also a major physical feature of the syndrome.

Other health conditions associated with the syndrome include heart defects, in 50% of individuals, feeding issues, low muscle gone and thyroid abnormalities.

Possible clinical traits/features:
Strabismus, Sparse and thin eyebrow, Ptosis, Tented upper lip vermilion, Respiratory failure, Ventricular septal defect, Arachnodactyly, Abnormality of the foot, Cleft palate, Camptodactyly of toe, Wide nasal bridge, Advanced eruption of teeth, Atrial septal defect, Blepharophimosis, Nystagmus, Open mouth, Sensorineural hearing impairment, Widely spaced teeth, Seizure, Proteinuria, Stenosis of the external auditory canal, Thin vermilion border, Scrotal hypoplasia, Autosomal dominant inheritance, Pes planus, Patellar aplasia, Cryptorchidism, Conductive hearing impairment, Epicanthus, Everted lower lip vermilion, Clinodactyly of the 5th finger, Smooth philtrum, Feeding difficulties in infancy, External ear malformation, Atresia of the external auditory canal, Delayed eruption of teeth, Hypermetropia, Full cheeks, Depressed nasal bridge, Cognitive impairment, Visual impairment, Hypothyroidism, Hearing impairment, Short stature, Intellectual disability, Abnormality of dental enamel, Joint laxity, Joint hypermobil

How does someone get tested for Ohdo syndrome, SBBYS Variant (SBBYSS)?

The initial testing for Ohdo syndrome, SBBYS Variant (SBBYSS) 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 Ohdo syndrome, SBBYS Variant (SBBYSS)

Strabismus, Sparse and thin eyebrow, Ptosis, Tented upper lip vermilion, Respiratory failure, Ventricular septal defect, Arachnodactyly, Abnormality of the foot, Cleft palate, Camptodactyly of toe, Wide nasal bridge, Advanced eruption of teeth, Atrial septal defect, Blepharophimosis, Nystagmus, Open mouth, Sensorineural hearing impairment, Widely spaced teeth, Seizure, Proteinuria, Stenosis of the external auditory canal, Thin vermilion border, Scrotal hypoplasia, Autosomal dominant inheritance, Pes planus, Patellar aplasia, Cryptorchidism, Conductive hearing impairment, Epicanthus, Everted lower lip vermilion, Clinodactyly of the 5th finger, Smooth philtrum, Feeding difficulties in infancy, External ear malformation, Atresia of the external auditory canal, Delayed eruption of teeth, Hypermetropia, Full cheeks, Depressed nasal bridge, Cognitive impairment, Visual impairment, Hypothyroidism, Hearing impairment, Short stature, Intellectual disability, Abnormality of dental enamel, Joint laxity, Joint hypermobil

"Say-Barber-Biesecker-Young-Simpson syndrome (Ohdo syndrome variant) is characterized by dysmorphic features (blepharophimosis, bulbous nasal tip, small mouth), dislocated or hypoplastic patellae, dental abnormalities, various additional congenital abnormalities, and intellectual disability. Some of the affected individuals have an immobile face. This autosomal dominant syndrome is caused by heterozygous mutations in the KAT6B gene.

Young and Simpson (1987) described a female infant with microcephaly, blepharophimosis, small, low-set, posteriorly rotated ears, a bulbous nose, and micrognathia. There was also an ASD, VSD, intellectual disability and hypothyroidism.

Fryns and Moerman (1988) described a similar male case. Apart from the hypoplastic teeth, these infants have some similarities to Ohdo (1986) (qv).

Cavalcanti (1989) reported a 7-month-old male with features of the condition. He also had postaxial polydactyly of the left foot and both hands.

Bonthron et al., (1993) reported a further possible case with an AV-canal defect. The parents were consanguineous.

Moncla et al., (1995) published a 5-month-old boy with a similar combination of features where a terminal deletion of 3p was demonstrated. The authors noted similarities to other cases with 3p25-pter deletions. A patient with a 1p36 terminal deletion has also been reported (Robinson et al., 2008).

Mansuno et al., (1999) reported unrelated male and female cases with features of the condition. In both cases, MRI scans of the brain showed patchy lesions of the subcortical white matter with high signal intensity on T2 weighted imaging.

Kondoh et al., (2000) published a further case. Hypothyroidism was only transient. The thyroid appeared to be anatomically normal. Growth was almost normal. There was also macular degeneration of the fundus, a torticollis, mild talipes equinovarus, and patella dislocation.

Marques-de-Faria et al., (2000) reported a male infant with features overlapping with Ohdo syndrome and Young-Simpson syndrome.

Genitopatellar syndrome is an allelic disorder to SBBYS syndrome.

Yilmaz et al., (2015) reported three patients with typical SBBYS syndrome and the KAT6B c.3147G>A synonymous variant. The mutation induces aberrant splicing through the use of a cryptic exonic splice acceptor site created by the sequence variant. The authors concluded that this mutation represents a mutational hot spot in SBBYS syndrome. Most SBBYS syndrome-causing mutations are clustered in the large exon 18 of KAT6B and almost exclusively lead to predicted protein truncation.

Preiksaitiene et al., (2016) described a female patient with a 5.2 Mb deletion of the 10q22.1q22.3 region including KAT6B. The authors compared the clinical presentation of this patient to four previous patients with similar deletions. The deletion sizes in the five patients varied from 2.6 Mb to 7.9 Mb. The features observed in all the patients included hypotonia and developmental delay, genital anomalies, and characteristic facial dysmorphism. Occasional features included long thumbs/great toes, mask-like face, lacrimal duct anomalies, patellar hypoplasia/agenesis, congenital heart defect, dental anomalies, hearing loss, thyroid anomalies, cleft palate, genital anomalies, and short stature.

Radvanszky et al. (2017) report a girl with multiple congenital anomalies and additional phenotypic features overlapping both SBBYSS and GTPTS. She had a truncating variant in the last KAT6B exon.

Lundsgaard et al., (2017) described a girl with dysmorphic features, atrial septal defect and developmental delay caused by a heterozygous protein-truncating mutation in the KAT6B gene. Clinical features included polyhydramnios during pregnancy, developmental delay, hypotonia, feeding problems, atrial septal defect, chronic otitis media, and hypermetropia. Dysmorphic features were hypertelorism, inverse epicanthal folds, small teeth, blepharophimosis, eversion of the lateral part of the eyelid, arched and laterally sparse eyebrows, long first finger and short fifth finger, and overlapping of the fourth toe over the third toe. Brain MRI revealed hypomyelination and a short corpus callosum.

Yong Rok Kim et al., (2017) described a familial case. The proband was a 3-year-old female patient with developmental delay. She had an immobile face, blepharophimosis, ptosis, a broad and flat nasal bridge, and a low set of large protruding ears. Her father also had a similar face, intellectual disability, and a contracture deformity in the metacarpophalangeal joints. The paternal grandmother and uncle had intellectual disability. The authors identified a missense mutation in the KAT6B gene in affected family members.

* 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!