Adams-Oliver syndrome 2; AOS2

What is Adams-Oliver syndrome 2; AOS2?

Adams-Oliver syndrome 2; AOS2 is a rare disease.
There are currently no additional known synonyms for this rare genetic disease.

Adams-Oliver syndrome is inherited in an autosomal dominant or an autosomal recessive manner. Autosomal recessive forms of the disease are more severe. It is characterized by aplasia cutis congenita, terminal transverse limb defects and additional congenital abnormalities.
Amor et al., (2000) reported a brother and sister with features of Adams-Oliver syndrome, but with global development delay, seizures, and evidence of a neuronal migration defect on brain scanning. One sib had aplasia cutis congenita of the scalp and transverse limb defects and the other had short fingers and toes and developed lymphoedema of the right leg. The authors suggest that this is a separate autosomal recessive form of the condition.
Klinger and Merlob (1998) reported two sibs with normal parents. One had aplasia cutis of the scalp and the other terminal lower limb defects. Both had cutis mamorata. The parents were clinically normal. Although autosomal recessive inheritance was suggested, incomplete penetrance or mosaicism in one of the parents cannot be excluded. Tekin et al., (1999) reported a family with affected sibs and unaffected consanguineous Turkish parents and Temtamy et al., (2007) reported further evidence for recessive inheritance. Unay et al., (2001) reported another Turkish family where a seven-year-old girl had features of Adams-Oliver syndrome, but with microcephaly, epilepsy, intra-cranial calcification and mental retardation. The parents were double first cousins. It is possible that this child had two separate genetic conditions.
A further family from Turkey with second cousin parents where there were three affected fetuses picked up by ultrasound at around 22-37 weeks of pregnancy with normal parents, was reported by Becker et al., (2002).
McGoey and Lacassie (2008) reported a sib-pair and review the CND findings in the sib-pairs reported in the literature. Periventricular calcification, cortical malformation, agenesis of the corpus callosum, and other evidence of ischemia were found. The phenotype on the possibly recessive cases seemed more severe. Brancati et al., (2008) reported a severe case with a neuronal migration defect.
Two unrelated patients, born to cousin parents reported by Shaheen et al., (2011) had mutations in DOCK6. The first case had, in addition, severe delay, microcephaly and optic atrophy, whereas the second was more typical. Families without DOCK6 mutations were evaluated by Shaheen et al., (2013). They mapped to 3p14.1 and mutations were found in EOGT which encodes O-GlcNAc. Cohen et al., (2014) described further families homozygous for EOGT mutations. A patient homozygous for a DOCK6 mutation had a thrombotic vasculopathy (Lehman et al., 2014). Ten patients from eight families with DOCK6 mutations have confirmed the pathogenicity of DOCK6 (Sukalo et al., 2015).
NOTE- see also 'Orstavik, (1995) for a similar, or the same syndrome (the Sukalo et al., 2015 study included this family and a DOCK6 mutation was found)
Jones et al., (2017) described a patient with compound heterozygous mutations in the DOCK6 gene and IUGR, brachydactyly of right second distal phalanx, hypoplastic nails, calcified papules on several fingers and toes, aplasia cutis congenita, large patent ductus arteriosus and patent foramen ovale. Brain MRI showed periventricular calcifications, bilateral inferior temporal cortical infarcts and polymicrogyria.
Hassed et al., (2017) reviewed 385 previously reported patients (139 non-familial and 246 familial probands and family members) and 13 unreported individuals with Adams-Oliver syndrome. Clinical features were aplasia cutis congenita (99%), small nails (51%), cutaneous syndactyly, bony syndactyly, or both (29%), brain anomalies (35%) and microcephaly (7%). Central nervous system abnormalities included calvarial defect without brain anomaly (25%), calvarial defect with brain anomaly (11%), microcephaly with other anomalies (6%), calcifications secondary to vascular sequelae (5%), enlarged ventricles (5%), isolated microcephaly (4%) and thin or absent corpus callosum (4%). Most prevalent heart and vascular defects were cutis marmorata telangiectasia congenita (19%), prominent vessels (8%), bicuspid or parachute aortic valve (6%), ventricular septal defect (6%), tortuous vessels (5%), and atrial septal defect (5%); no anomalies were found in 10%. Liver abnormalities were present in 11% of probands. Haemorrhage was listed as the cause of death for 5/25 deaths reported.
Pisciotta et. al., (2018) described a male patient with a novel compound heterozygous mutation in the DOCK6 gene.

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* This information is courtesy of the L M D.

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What gene changes cause Adams-Oliver syndrome 2; AOS2?

The syndrome is inherited in the following inheritance pattern/s:

Autosomal Recessive - Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.

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 that occurs during the reproductive process.

OMIM Number - 614219 (please check the OMIM page for updated information)

The syndrome can be caused by mutations in the following gene/s location/s:

What are the main symptoms of Adams-Oliver syndrome 2; AOS2?

The typical symptoms of the syndrome are:
Cerebral atrophy, Bulbous nose, Depressed nasal bridge, Developmental cataract, Cutis marmorata, Muscular hypotonia, Micrognathia, Microphthalmia, Low anterior hairline, Low-set ears, Hypertelorism, Global developmental delay, Polymicrogyria, Protruding ear, Autosomal recessive inheritance, Oligohydramnios, Optic atrophy, Seizure, Single transverse palmar crease, Strabismus, Narrow palpebral fissure, Macrocephaly, Microcephaly, Small nail, Retrocerebellar cyst

How does someone get tested for Adams-Oliver syndrome 2; AOS2?

The initial testing for Adams-Oliver syndrome 2; AOS2 can begin with facial genetic analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the type of genetic testing needed. 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.

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