Aplasia cutis congenita (ACC), which is the congenital localized absence of skin and lesions of skull, and terminal transverse limb defects (TTLD) are the key features of AOS . However, these traits are not unique to AOS. For example, ACC can present in Johanson-Blizzard syndrome. A scalp defect can sometimes also be observed in trisomy 13, deletion of the short arm of chromosome 4, and the Wolf-Hirschhorn syndrome .
Picture showing scar of ACC
The most common site of ACC is the vertex, which is the upper surface of the head. The scalp defect is often associated with an underlying skull defect, and the degrees of severity vary with the head structures involved. It is noteworthy that a bony defect can present without scalp defect, and a skull X-ray is suggested to find out the extent of the anomaly .
In most cases with scalp defect but not brain and cranial defect, patients can be managed conservatively. Nevertheless, hemorrhage or infection can lead to severe manifestations with a mortality rate of between 20% and 55% [2,3].
Pictures showing terminal transverse limb defects, including the absence of toenail.
Asymmetrical limb defects on both sides are commonly observed. The severity ranges from minor nail abnormalities to absence of long bone, including hypoplastic nails, cutaneous syndactyly, bony syndactyly, transverse reduction defects, ectrodactyly, polydactyly, and brachydactyly .
Some other features are also observed in AOS cases. Since AOS is a rare disease and its spectrum is very broad, the features listed below do not form a complete list of AOS related conditions. Also, keep in mind that these features are NOT diagnostic and can relate to other problems.
Cutis marmorata telangiectatica congenita (CMTC)
CMTC is a rare condition with complex blood vessel malformation, showing a net-like, segmental pattern. The pathogenesis of CMTC is believed to be a vascular defect. CMTC presents in 12-21% AOS patients .
Pictures showing CMTC
Congenital cardiac malformations
The structural cardiac abnormalities in AOS vary widely, but there is a common association between cardiac defects and vascular defects in AOS, providing evidence to the vascular pathogenic hypothesis. Congenital cardiac defect presents in 13-20% AOS patients. The potential pathology will be discussed in the Vasculopathy section [2,4].
Both structural, such as incomplete development or absence of blood vessels, and functional abnormalities, Pulmonary Hypertension (PH) for example, are found in past studies . Vascular abnormalities are associated to many other features observed in AOS individuals.
Neurological involvement is more commonly reported in autosomal recessive individuals than in autosomal dominant individuals with AOS. In autosomal dominant individuals, neurological problems tend to occur with other vascular abnormalities. In autosomal recessive individuals, a more server neurological condition, including microcephaly, mental retardation, and intracranial abnormalities, can be observed .
Some AOS patients also have ophthalmological findings. Some examples are cataracts, esotropia , microphthalmia. Clinical examinations can reveal additional features that are harder to observe: optic disk drusen, retinal folds, bilateral retinal detachment, unususal choroidal architecture, and rod dystrophy [2,5].