Chorioretinopathy, Ataxia, and Hypogonadism

Clinical Characteristics

Ocular Features:

The retinal pigment epithelium changes may be seen as early as the first decade of life with pigment deposition resembling bone spicules. These changes as well as atrophy of the choriocapillaris are most apparent in the posterior pole and extend into the midperiphery. Retinal vessels may be attenuated. Progressive loss of vision, dyschromatopsia, and photophobia are the primary ocular symptoms. Night blindness and constricted visual fields are noted by some patients. The ERG shows subnormal and sometimes absent photopic and scotopic responses. Nystagmus is present in more than half of individuals.

Systemic Features:

Difficulties with balance, intention tremors, and scanning speech are evident in adolescence or early adult life. Cerebellar ataxia is present in nearly 40 percent of individuals. However, there is marked variability in the rate of progression. Many patients have atrophy of the superior and dorsal areas of the cerebellar vermis and atrophy of the cerebellar hemispheres as noted on MRIs. Hypogonadotrophic hypogonadism is a feature with delayed puberty noted in 26 percent. In the absence of exogenous hormone administration, secondary sexual characteristics fail to develop.

Genetics

Autosomal recessive inheritance has been suggested on the basis of consanguinity in three families, multiple affected sibs born to normal parents, and a 1:1 sex ratio. Homozygous and compound heterozygous mutations in PNPLA6 [1] (19p13.2) have been found in several patients.

Mutations in PNPLA6 [1] occur in other conditions including a form of Bardet-Biedl Syndrome [2] (209900 [3]), and Trichomegaly Plus Syndrome [4] (275400 [5]), in this database.

Treatment

Treatment Options:

The use of appropriate hormones can stimulate the development of normal secondary sexual characteristics and may restore reproductive function. At least two female patients gave birth to a child following hormone substitution.

Low vision aids could be helpful in selected patients.

References

Article Title:

Boucher-Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature [6]

Tarnutzer AA, Gerth-Kahlert C, Timmann D, Chang DI, Harmuth F, Bauer P, Straumann D, Synofzik M. Boucher-Neuhauser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature. J Neurol. 2014 Oct 31. [Epub ahead of print].

PubMed ID:

25359264

Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia [7]

Deik A, Johannes B, Rucker JC, Sanchez E, Brodie SE, Deegan E, Landy K, Kajiwara Y, Scelsa S, Saunders-Pullman R, Paisan-Ruiz C. Compound heterozygous PNPLA6 mutations cause Boucher-Neuhauser syndrome with late-onset ataxia. J Neurol. 2014 Sep 30. [Epub ahead of print].

PubMed ID:

25267340

PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum [8]

Synofzik M, Gonzalez MA, Lourenco CM, Coutelier M, Haack TB, Rebelo A, Hannequin D, Strom TM, Prokisch H, Kernstock C, Durr A, Schols L, Lima-Martinez MM, Farooq A, Schule R, Stevanin G, Marques W Jr, Zuchner S. PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. Brain. 2013 Dec 19. [Epub ahead of print].

PubMed ID:

24355708

Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome [9]

Rump P, Hamel BC, Pinckers AJ, van Dop PA. Two sibs with chorioretinal dystrophy, hypogonadotrophic hypogonadism, and cerebellar ataxia: Boucher-Neuhauser syndrome. J Med Genet. 1997 September; 34(9): 767-771.

PubMed ID:

9321767

Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy [10]

Salvador F, Garcia-Arumi J, Corcostegui B, Minoves T, Tarrus F. Ophthalmologic findings in a patient with cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Am J Ophthalmol. 1995 Aug;120(2):241-4.

PubMed ID:

7639308