Laurence Moon syndrome is a rare genetic disease of a multisystemic nature that features hypopituitarism, obesity, mental retardation, ataxia, and retinal dystrophy. It is categorized under the wider spectrum of PNPLA6-related disorders and inherited via the autosomal recessive inheritance pattern. Definite diagnosis is possible only via genetic testing.
Laurence Moon syndrome (LMS) was first described in 1866, as a disorder that leads to obesity, mental retardation, and retinal dystrophy, accompanied by hypoplastic genitalia and gait disturbance . Although historically connected to Bardet-Biedl syndrome, which is also a PNPLA6-related disorder, patients affected with LMS do not display the characteristic of polydactyly and the two disorders are presently considered as distinct; LMS patients are known, however, to exhibit variable disorder patterns, with one or more manifestations missing, even in the same family   .
In the majority of the presently known Laurence-Moon syndrome cases, the disease has a childhood onset, characterized by cerebellar ataxia, spastic paraplegia, peripheral neuropathy, and chorioretinopathy . Hypopituitarism frequently coexists, leading to hypogonadism and obesity. In one specific case, patients of the same family were described to exhibit retinopathy, subaverage intellectual ability, first metacarpal hypoplasia, abnormal development of genitalia, and short stature . A synopsis of the LMS-related manifestations includes:
Laurence Moon syndrome is an inherited disorder classified under the PNPLA6-related disorders. An accurate diagnosis is achieved through genetic testing, accompanied by an evaluation of the clinical signs and symptoms, as well as laboratory tests and imaging studies . Blood tests and imaging do not contribute to the diagnosis of LMS per se but help to evaluate and pinpoint manifestations.
Also, the clinical picture does not suffice to diagnose Laurence Moon syndrome. However, it does suggest which individuals should undergo further evaluation. Patients who present with difficulty in movement coordination, dizziness, speech problems, visual impairment, peripheral neuropathy, lower limb spasticity, and hypopituitarism are likely candidates for LMS.
Serum laboratory analysis is directed towards the detection of hypopituitarism in infants or children with evident clinical indications, such as short stature and hypoplastic genitalia. Low concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are found in the majority of LMS patients . Some patients will additionally undergo a magnetic resonance imaging (MRI) brain scan which could illustrate an underdeveloped pituitary .
The definitive LMS diagnosis is rendered possible when genetic testing reveals biallelic PNPLA6 pathogenic variants. This can be achieved via sequence analysis of the PNPLA6 gene, completed with a deletion/duplication analysis if necessary, or via a multi-gene sequencing panel .