| Gómez-López-Hernández syndrome | |
|---|---|
| Other names | Craniosynostosis-alopecia-brain defect syndrome, Craniosynostosis-alopecia-brain defect syndrome |
 | |
| A young girl showing characteristic bilateral alopecia and angled ears | |
Gómez–López-Hernández syndrome (GLH) or cerebellotrigeminal-dermal dysplasia is a rare neurocutaneous (Phakomatosis) disorder affecting the trigeminal nerve and causing several other neural and physical abnormalities.[1] Gómez–López-Hernández syndrome has been diagnosed in only 34 people.[2] Cases of Gómez–López-Hernández syndrome may be under-reported as other diseases share the characteristics of cerebellar malformation shown in Gómez–López-Hernández syndrome.[1][2] Gómez–López-Hernández syndrome was first characterized in 1979.[3]
Physical characteristics of the syndrome can vary and are not universal. People with Gómez–López-Hernández syndrome often have a short skull (brachycephaly), thin lips, low-set and posterior-angled ears, and scalp alopecia above both ears.[4] This bilateral scalp alopecia is the most consistent physical characteristic of Gómez–López-Hernández syndrome.[5] In addition to the shortness of the skull, it is also misshapen and often flattened on the back.[2] Some people with Gómez–López-Hernández syndrome also have wide-set (hypertelorism) and crossed eyes (strabismus).[4] Scarring or clouding of the cornea occurs in the majority of people with Gómez–López-Hernández syndrome.[6] A short stature is common.[1]
Aside from the physical characteristics of the eyes there is also less sensation in the eyes when stimulated.[4] The eyes also show low motor control (ataxia).[4] Along with ataxia comes a lack of coordination or ability to judge the distance of objects (dysmetria).[6] MRIs show a constant feature of rhombencephalosynapsis–a condition marked by the absence or partial absence of the cerebellar vermis and varying degrees of fusion in the cerebellum in every case of Gómez–López-Hernández syndrome.[4][7][8] Also absent are the trigeminal nerve of the trigeminal cave and the foramen rotundum, causing abnormal sensations on the forehead and the corneas.[6][8] One Gómez–López-Hernández syndrome case in Japan also presents fever-induced seizures.[9] Others may or may not present with non-fever-induced seizures.[4] Malformations of motor centers in the brain cause reduced muscle strength (hypotonia).[8] Eleven of fifteen people in one study showed moderate-to-severe intellectual disability.[6] In cases where it has been noted, head nodding is present.[6] Hydrocephalus and enlargement of the ventricular system is consistently present.[6] A reduced corpus callosum is present in some cases (agenesis of the corpus callosum).[6]
Gómez–López-Hernández syndrome is associated with irritability, anxiety, insomnia, and self-harming behavior.[4] Developmental disabilities often present as intellectual disability with social, occupational, and learning disabilities.[4] Reduced eye sensation may cause self-harm to the eyes; one patient is on record as having put her fingers into her eyes to the point of causing additional corneal damage beyond what is normally characteristic of the syndrome.[4]
The exact causes of Gómez–López-Hernández syndrome are currently unknown. Mutations of the ACP2 gene have been implicated but not confirmed.[4] One case of siblings — both with Gómez–López-Hernández syndrome — has been observed, showing possible evidence of recessive inheritance.[2] The Brazilian parents of these siblings showed some degree of inbreeding, being first cousins.[2] Five of the 34 people diagnosed with Gómez–López-Hernández syndrome have also come from Brazil.[2] Lack of expression from the WNT1, FGF8, FGF17, OTX2, fgf8, and fgf17 genes have all been implicated as possibly being the cause of cerebellum fusion.[4]
All cases of Gómez–López-Hernández syndrome present scalp alopecia, varying degrees of low-set ears and most have a flattened skull.[10] Scalp alopecia has been present in all but one case though it can be asymmetrical or, in a single case, only present on one side.[5] All people with Gómez–López-Hernández syndrome also have delayed motor milestones.[10] All people with the syndrome have malformation of the cerebellum.[10] Certain characteristics are often present in those with Gómez–López-Hernández syndrome but are not consistent enough to rule out the syndrome if they are not present. Reduced eye sensation, or trigeminal anesthesia, is present in about three-quarters of people with Gómez–López-Hernández syndrome.[5] Malformations of the skull, rotations of the ears, and abnormalities of the face are features that vary widely and cannot be used alone to diagnose Gómez–López-Hernández syndrome as these characteristics overlap with some other diseases.[5] Gómez–López-Hernández syndrome has been diagnosed as early as 21 weeks with prenatal MRI showing fusion of the cerebellum and later confirmed postnatal with skull and facial abnormalities at six weeks.[11]
Gómez–López-Hernández syndrome is rare and similar to other developmental disabilities. Management is similar to other developmental disabilities as there is no cure for malformations of the brain. Gómez–López-Hernández syndrome has been diagnosed mostly in poorer countries.[4] There have been no documented attempts made to educate children with the syndrome (when intellectual disability is present) to establish a baseline of intellectual ability due to these socioeconomic problems.[4]
The oldest person who has been diagnosed with Gómez–López-Hernández syndrome was 29 years old at the time of his assessment in 2008.[4] Most people with Gómez–López-Hernández syndrome are consistently low weight (3rd-25th percentile) and low stature due to a deficiency of growth hormone.[4] Low mobility is often an issue.[4] The cause of low mobility is thought to be neurological, therefore bone structure is not greatly affected.[4] Seizures may or may not be present and can result in injuries for those who are more mobile.[4] ADHD and bipolar disorder — which are sometimes present — can lead to dangerous behavior or outbursts.[4] While most people with Gómez–López-Hernández syndrome show moderate intellectual disability, one case (age 14) has resulted in normal learning and social skills without intervention.[4]
Most cases have been diagnosed in Latin America with five of the thirty-four being from Brazil.[2] Two of these Brazilians are related by blood (consanguinity) suggesting the possibility of Mendelian inheritance.[2] There has been one case of a Japanese patient with Gómez–López-Hernández syndrome so far.[9] Two Armenian cases and two from Europe have been identified, signaling that the perceived prevalence in Latin America may be short-lived as better diagnostic techniques and information about this syndrome become more widespread.[5] Recently, a case of Gómez–López-Hernández syndrome was reported from India as well.[12]
Gómez–López-Hernández syndrome is named for Manuel Rodríguez Gómez[13] and Alejandro López-Hernández.[14]
